Browse publications by year: 2015

  1. A novel rat model of Alzheimer's disease based on lentiviral-mediated expression of mutant APP
    Parsi S, Pandamooz S, Heidari S, Naji M, Morfini G, Ahmadiani A, et al.
    Neuroscience, 2015 Jan 22;284:99-106.
    PMID: 25270904 DOI: 10.1016/j.neuroscience.2014.09.045
    Alzheimer's disease (AD) is characterized by progressive and irreversible cognitive and memory impairment. The discovery of familial forms of AD (fAD) in association with specific gene mutations facilitated the generation of numerous rodent models. These models in turn proved valuable for the study of molecular mechanisms underlying AD pathogenesis, and facilitated translational research and preclinical drug development. This study aimed to introduce a new rat model of AD simulating some aspects of the sporadic cases of disease.
    MeSH terms: Alzheimer Disease/genetics*; Alzheimer Disease/physiopathology*; Analysis of Variance; Animals; Avoidance Learning; Disease Models, Animal*; Glial Fibrillary Acidic Protein/metabolism; Humans; Male; Mutation/genetics*; Lentivirus/genetics; Amyloid beta-Protein Precursor/genetics*; Rats, Wistar; Maze Learning/physiology; Rats; Rats, Transgenic
  2. Fulltext A prawn core histone 4: derivation of N- and C-terminal peptides and their antimicrobial properties, molecular characterization and mRNA transcription
    Chaurasia MK, Palanisamy R, Bhatt P, Kumaresan V, Gnanam AJ, Pasupuleti M, et al.
    Microbiol Res, 2015 Jan;170:78-86.
    PMID: 25271126 DOI: 10.1016/j.micres.2014.08.011
    This study investigates the complete molecular characterization including bioinformatics characterization, gene expression, synthesis of N and C terminal peptides and their antimicrobial activity of the core histone 4 (H4) from freshwater giant prawn Macrobrachium rosenbergii (Mr). A cDNA encoding MrH4 was identified from the constructed cDNA library of M. rosenbergii during screening and the sequence was obtained using internal sequencing primers. The MrH4 coding region possesses a polypeptide of 103 amino acids with a calculated molecular weight of 11kDa and an isoelectric point of 11.5. The bioinformatics analysis showed that the MrH4 polypeptide contains a H4 signature at (15)GAKRH(19). Multiple sequence alignment of MrH4 showed that the N-terminal (21-42) and C-terminal (87-101) antimicrobial peptide regions and the pentapeptide or H4 signature (15-19) are highly conserved including in humans. The phylogenetic tree formed two separate clades of vertebrate and invertebrate H4, wherein MrH4 was located within the arthropod monophyletic clade of invertebrate H4 groups. Three-dimensional model of MrH4 was established using I-TASSER program and the model was validated using Ramachandran plot analysis. Schiffer-Edmundson helical wheel modeling was used to predict the helix propensity of N (21-42) and C (87-101) terminal derived Mr peptides. The highest gene expression was observed in gills and is induced by viral [white spot syndrome baculovirus (WSBV) and M. rosenbergii nodovirus (MrNV)] and bacterial (Aeromonas hydrophila and Vibrio harveyi) infections. The N and C terminal peptides were synthesized and their antimicrobial and hemolytic properties were examined. Both peptides showed activity against the tested Gram negative and Gram positive bacteria; however, the highest activity was noticed against Gram negative bacteria. Among the two peptides used in this study, C-terminal peptide yielded better results than the N-terminal peptide. Therefore, C terminal peptide can be recommended for the development of an antimicrobial agent.
    MeSH terms: Amino Acid Sequence; Animals; Anti-Infective Agents/pharmacology; Anti-Infective Agents/chemistry; Base Sequence; Hemolysis/drug effects; Microbial Sensitivity Tests; Molecular Sequence Data; Peptides/pharmacology; Peptides/chemistry; Phylogeny; RNA, Messenger/genetics; RNA, Messenger/chemistry; Transcription, Genetic; Gene Expression; Sequence Alignment; Protein Structure, Secondary; DNA, Complementary/genetics; DNA, Complementary/chemistry; Palaemonidae*
  3. Stray animal and human defecation as sources of soil-transmitted helminth eggs in playgrounds of Peninsular Malaysia
    Mohd Zain SN, Rahman R, Lewis JW
    J Helminthol, 2015 Nov;89(6):740-7.
    PMID: 25273274 DOI: 10.1017/S0022149X14000716
    Soil contaminated with helminth eggs and protozoan cysts is a potential source of infection and poses a threat to the public, especially to young children frequenting playgrounds. The present study determines the levels of infection of helminth eggs in soil samples from urban and suburban playgrounds in five states in Peninsular Malaysia and identifies one source of contamination via faecal screening from stray animals. Three hundred soil samples from 60 playgrounds in five states in Peninsular Malaysia were screened using the centrifugal flotation technique to identify and determine egg/cyst counts per gram (EPG) for each parasite. All playgrounds, especially those in Penang, were found to be contaminated with eggs from four nematode genera, with Toxocara eggs (95.7%) the highest, followed by Ascaris (93.3%), Ancylostoma (88.3%) and Trichuris (77.0%). In addition, faeces from animal shelters were found to contain both helminth eggs and protozoan cysts, with overall infection rates being 54% and 57% for feline and canine samples, respectively. The most frequently occurring parasite in feline samples was Toxocara cati (37%; EPG, 42.47 ± 156.08), while in dog faeces it was Ancylostoma sp. (54%; EPG, 197.16 ± 383.28). Infection levels also tended to be influenced by season, type of park/playground and the texture of soil/faeces. The occurrence of Toxocara, Ancylostoma and Trichuris eggs in soil samples highlights the risk of transmission to the human population, especially children, while the presence of Ascaris eggs suggests a human source of contamination and raises the issue of hygiene standards and public health risks at sites under investigation.
    MeSH terms: Animals; Cats; Defecation; Dogs; Feces/parasitology*; Feces/chemistry; Helminthiasis/parasitology*; Helminthiasis/transmission; Helminths/classification; Helminths/genetics; Helminths/isolation & purification*; Humans; Malaysia; Ovum/classification; Play and Playthings; Public Health; Seasons; Soil/parasitology*; Soil/chemistry
  4. Novel lipase purification methods - a review of the latest developments
    Tan CH, Show PL, Ooi CW, Ng EP, Lan JC, Ling TC
    Biotechnol J, 2015 Jan;10(1):31-44.
    PMID: 25273633 DOI: 10.1002/biot.201400301
    Microbial lipases are popular biocatalysts due to their ability to catalyse diverse reactions such as hydrolysis, esterification, and acidolysis. Lipases function efficiently on various substrates in aqueous and non-aqueous media. Lipases are chemo-, regio-, and enantio-specific, and are useful in various industries, including those manufacturing food, detergents, and pharmaceuticals. A large number of lipases from fungal and bacterial sources have been isolated and purified to homogeneity. This success is attributed to the development of both conventional and novel purification techniques. This review highlights the use of these techniques in lipase purification, including conventional techniques such as: (i) ammonium sulphate fractionation; (ii) ion-exchange; (iii) gel filtration and affinity chromatography; as well as novel techniques such as (iv) reverse micellar system; (v) membrane processes; (vi) immunopurification; (vi) aqueous two-phase system; and (vii) aqueous two-phase floatation. A summary of the purification schemes for various bacterial and fungal lipases are also provided.
    MeSH terms: Bacterial Proteins/isolation & purification; Bacterial Proteins/metabolism; Bacterial Proteins/chemistry; Chromatography/methods*; Fungal Proteins/isolation & purification; Fungal Proteins/metabolism; Fungal Proteins/chemistry; Lipase/isolation & purification*; Lipase/metabolism; Lipase/chemistry; Membranes, Artificial; Micelles; Chemical Precipitation*
  5. Fulltext A web-based dietary intervention for people with type 2 diabetes: development, implementation, and evaluation
    Ramadas A, Chan CK, Oldenburg B, Hussien Z, Quek KF
    Int J Behav Med, 2015 Jun;22(3):365-73.
    PMID: 25274015 DOI: 10.1007/s12529-014-9445-z
    BACKGROUND: Diabetes is becoming a very important health issue in rapidly developing nations and there is an urgent need to improve overall diabetes self-management education in these countries. Although e-health is an emerging theme, only a few successful web-based studies on diabetes self-management have been reported.
    PURPOSE: We describe the development, implementation, and process evaluation of an Internet-delivered dietary intervention program (myDIDeA) for diabetic patients in a developing country.
    METHOD: Specific dietary components to be included in the intervention module were first identified through a comprehensive review of literature and guidelines. The lesson plans and the study website were then developed based on the evidence, Transtheoretical Model's Stages of Change and user-centered design approach. Finally, the effectiveness of the website was tested through a randomized-controlled trial to promote dietary change in patients with type 2 diabetes. The participants in the intervention group (n = 66) were given access to myDIDeA for 6 months. Process evaluation in form of intervention adherence and program reception were conducted at post intervention.
    RESULTS: The response rate for the process evaluation was 89%. On average, each participant logged in at least once for each lesson plan and spent almost 12 min on the site. The participants' content satisfaction, acceptability, and usability scores were satisfactory. The primary outcome of the trial, Dietary Knowledge, Attitude, and Behavior score was strongly correlated with content satisfaction (r = 0.826, p 
    MeSH terms: Chronic Disease; Diabetes Mellitus, Type 2/diet therapy*; Diet; Female; Humans; Malaysia; Male; Middle Aged; Self Care/methods; Health Behavior*; Internet*
  6. Fulltext A genome-wide pleiotropy scan for prostate cancer risk
    Panagiotou OA, Travis RC, Campa D, Berndt SI, Lindstrom S, Kraft P, et al.
    Eur Urol, 2015 Apr;67(4):649-57.
    PMID: 25277271 DOI: 10.1016/j.eururo.2014.09.020
    BACKGROUND: No single-nucleotide polymorphisms (SNPs) specific for aggressive prostate cancer have been identified in genome-wide association studies (GWAS).

    OBJECTIVE: To test if SNPs associated with other traits may also affect the risk of aggressive prostate cancer.

    DESIGN, SETTING, AND PARTICIPANTS: SNPs implicated in any phenotype other than prostate cancer (p≤10(-7)) were identified through the catalog of published GWAS and tested in 2891 aggressive prostate cancer cases and 4592 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). The 40 most significant SNPs were followed up in 4872 aggressive prostate cancer cases and 24,534 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) and 95% confidence intervals (CIs) for aggressive prostate cancer were estimated.

    RESULTS AND LIMITATIONS: A total of 4666 SNPs were evaluated by the BPC3. Two signals were seen in regions already reported for prostate cancer risk. rs7014346 at 8q24.21 was marginally associated with aggressive prostate cancer in the BPC3 trial (p=1.6×10(-6)), whereas after meta-analysis by PRACTICAL the summary OR was 1.21 (95% CI 1.16-1.27; p=3.22×10(-18)). rs9900242 at 17q24.3 was also marginally associated with aggressive disease in the meta-analysis (OR 0.90, 95% CI 0.86-0.94; p=2.5×10(-6)). Neither of these SNPs remained statistically significant when conditioning on correlated known prostate cancer SNPs. The meta-analysis by BPC3 and PRACTICAL identified a third promising signal, marked by rs16844874 at 2q34, independent of known prostate cancer loci (OR 1.12, 95% CI 1.06-1.19; p=4.67×10(-5)); it has been shown that SNPs correlated with this signal affect glycine concentrations. The main limitation is the heterogeneity in the definition of aggressive prostate cancer between BPC3 and PRACTICAL.

    CONCLUSIONS: We did not identify new SNPs for aggressive prostate cancer. However, rs16844874 may provide preliminary genetic evidence on the role of the glycine pathway in prostate cancer etiology.

    PATIENT SUMMARY: We evaluated whether genetic variants associated with several traits are linked to the risk of aggressive prostate cancer. No new such variants were identified.

    MeSH terms: Genotype; Glycine/genetics*; Glycine/metabolism; Humans; Male; Prognosis; Prostatic Neoplasms/genetics*; Risk Factors; Disease Progression; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide*; Genome-Wide Association Study/methods*
  7. Utilization of palm oil sludge through pyrolysis for bio-oil and bio-char production
    Thangalazhy-Gopakumar S, Al-Nadheri WM, Jegarajan D, Sahu JN, Mubarak NM, Nizamuddin S
    Bioresour Technol, 2015 Feb;178:65-9.
    PMID: 25278112 DOI: 10.1016/j.biortech.2014.09.068
    In this study, pyrolysis technique was utilized for converting palm oil sludge to value added materials: bio-oil (liquid fuel) and bio-char (soil amendment). The bio-oil yield obtained was 27.4±1.7 wt.% having a heating value of 22.2±3.7 MJ/kg and a negligible ash content of 0.23±0.01 wt.%. The pH of bio-oil was in alkaline region. The bio-char yielded 49.9±0.3 wt.%, which was further investigated for sorption efficiency by adsorbing metal (Cd(2+) ions) from water. The removal efficiency of Cd(2+) was 89.4±2%, which was almost similar to the removal efficiency of a commercial activated carbon. The adsorption isotherm was well described by Langmuir model. Therefore, pyrolysis is proved as an efficient tool for palm oil sludge management, where the waste was converted into valuable products.
    MeSH terms: Adsorption; Biotechnology/methods*; Cadmium/chemistry; Carbon/chemistry; Charcoal/chemistry*; Hydrogen-Ion Concentration; Ions; Gas Chromatography-Mass Spectrometry; Metals/chemistry; Plant Oils/chemistry*; Sewage/chemistry*; Temperature; Thermogravimetry; Water/chemistry; Biomass; Biofuels*
  8. Aptamers as a replacement for antibodies in enzyme-linked immunosorbent assay
    Toh SY, Citartan M, Gopinath SC, Tang TH
    Biosens Bioelectron, 2015 Feb 15;64:392-403.
    PMID: 25278480 DOI: 10.1016/j.bios.2014.09.026
    The application of antibodies in enzyme-linked immunosorbent assay (ELISA) is the basis of this diagnostic technique which is designed to detect a potpourri of complex target molecules such as cell surface antigens, allergens, and food contaminants. However, development of the systematic evolution of Ligands by Exponential Enrichment (SELEX) method, which can generate a nucleic acid-based probe (aptamer) that possess numerous advantages compared to antibodies, offers the possibility of using aptamers as an alternative molecular recognition element in ELISA. Compared to antibodies, aptamers are smaller in size, can be easily modified, are cheaper to produce, and can be generated against a wide array of target molecules. The application of aptamers in ELISA gives rise to an ELISA-derived assay called enzyme-linked apta-sorbent assay (ELASA). As with the ELISA method, ELASA can be used in several different configurations, including direct, indirect, and sandwich assays. This review provides an overview of the strategies involved in aptamer-based ELASA.
    MeSH terms: Allergens/isolation & purification; Antibodies/chemistry; Enzyme-Linked Immunosorbent Assay*; Ligands; Oligonucleotides/chemistry; Biosensing Techniques*; SELEX Aptamer Technique; Aptamers, Nucleotide/chemistry*
  9. Sequential hollow-fiber liquid phase microextraction for the determination of rosiglitazone and metformin hydrochloride (anti-diabetic drugs) in biological fluids
    Ben-Hander GM, Makahleh A, Saad B, Saleh MI, Cheng KW
    Talanta, 2015 Jan;131:590-6.
    PMID: 25281145 DOI: 10.1016/j.talanta.2014.08.037
    A new analytical method for the simultaneous determination of the antidiabetic drugs rosiglitazone (ROS) and metformin hydrochloride (MH) with marked differences in their affinity towards organic solvents (log P of 2.4 and -1.43, respectively) was developed. Prior to the HPLC separation, the drugs were subjected to a sequential hollow fiber liquid phase microextraction (HF-LPME) procedure. Two sequential HF-LPME approaches were considered, the preferred one involves the use of two vials containing solution mixtures for the extraction of ROS (vial 1) and MH (vial 2), respectively, but using the same fiber and acceptor phase. Important parameters that affect the extraction efficiency such as extracting solvent, donor phase conditions, HCl concentration, agitation, extraction time, addition of salt, etc. were studied. Under the optimum conditions, good enrichment factors (EF, 471 and 86.6 for ROS and MH, respectively) were achieved. Calibration curves were linear over the range 1-500 (r(2)=0.998) and 5-2500 ng mL(-1) (r(2)=0.999) for ROS and MH, respectively. The relative standard deviation values (RSD%) for six replicates were below 8.4%. Detection and quantitation limits based on S/N ratio of 3 and 10 were 0.12, 1.0 and 0.36, 3.0 ng mL(-1) for ROS and MH, respectively. The proposed method is simple, sensitive and opens up new opportunities for the microextraction of analytes with contrasting properties.
    MeSH terms: Calibration; Chromatography, High Pressure Liquid; Humans; Hydrogen-Ion Concentration; Hypoglycemic Agents/blood; Hypoglycemic Agents/urine; Metformin/blood*; Metformin/urine*; Solvents/chemistry; Thiazolidinediones/blood*; Thiazolidinediones/urine*; Liquid Phase Microextraction/methods*
  10. Three different patterns of CD4 recovery in a cohort of Chinese HIV patients following antiretroviral therapy - a five-year observational study
    Naftalin CM, Wong NS, Chan DP, Wong KH, Reidpath DD, Lee SS
    Int J STD AIDS, 2015 Oct;26(11):803-9.
    PMID: 25281539 DOI: 10.1177/0956462414553826
    To explore the heterogeneity of CD4 responses following highly active antiretroviral therapy, the patterns of CD4 recovery of HIV-1-infected Chinese patients who have been on their first antiretroviral regimen for ≥5 years were analysed. The CD4 trajectories were traced, smoothed and differentiated into three defined profiles. Half (56.3%) were 'satisfactory responders', with CD4 gain of >100 cells/μL and a peak of >350 cells/μL, plateauing before the end of Year 5. Thirty-three (24.4%) were 'continuing responders' whose CD4 rise persisted at Year 4-5. The remaining 26 (19.3%) were 'poor responders'. Presentation with AIDS before therapy was common not just among 'poor' but also paradoxically the 'continuing' responders. While a majority had responded well to antiretroviral therapy, older patients and those with AIDS diagnosis before initiation of therapy may never achieve a satisfactory level even with effective treatment. Categorization of HIV patients by their CD4 trajectory may support the prediction of immunological outcome over time, and ultimately inform treatment choices.
    MeSH terms: Adult; Aged; China/epidemiology; Female; Humans; Male; Middle Aged; RNA, Viral/analysis*; HIV-1/drug effects*; HIV-1/immunology; HIV Infections/drug therapy*; HIV Infections/ethnology; HIV Infections/immunology; Treatment Outcome; CD4 Lymphocyte Count*; Viral Load; Antiretroviral Therapy, Highly Active*; Asian Continental Ancestry Group/statistics & numerical data
  11. Enhancement of azo dye Acid Orange 7 removal in newly developed horizontal subsurface-flow constructed wetland
    Tee HC, Lim PE, Seng CE, Mohd Nawi MA, Adnan R
    J Environ Manage, 2015 Jan 1;147:349-55.
    PMID: 25284799 DOI: 10.1016/j.jenvman.2014.09.025
    Horizontal subsurface-flow (HSF) constructed wetland incorporating baffles was developed to facilitate upflow and downflow conditions so that the treatment of pollutants could be achieved under multiple aerobic, anoxic and anaerobic conditions sequentially in the same wetland bed. The performances of the baffled and conventional HSF constructed wetlands, planted and unplanted, in the removal of azo dye Acid Orange 7 (AO7) were compared at the hydraulic retention times (HRT) of 5, 3 and 2 days when treating domestic wastewater spiked with AO7 concentration of 300 mg/L. The planted baffled unit was found to achieve 100%, 83% and 69% AO7 removal against 73%, 46% and 30% for the conventional unit at HRT of 5, 3 and 2 days, respectively. Longer flow path provided by baffled wetland units allowed more contact of the wastewater with the rhizomes, microbes and micro-aerobic zones resulting in relatively higher oxidation reduction potential (ORP) and enhanced performance as kinetic studies revealed faster AO7 biodegradation rate under aerobic condition. In addition, complete mineralization of AO7 was achieved in planted baffled wetland unit due to the availability of a combination of aerobic, anoxic and anaerobic conditions.
    MeSH terms: Aerobiosis; Anaerobiosis; Azo Compounds/analysis; Azo Compounds/isolation & purification*; Benzenesulfonates/analysis; Benzenesulfonates/isolation & purification*; Biodegradation, Environmental; Coloring Agents/analysis; Coloring Agents/isolation & purification; Kinetics; Time Factors; Water Pollutants, Chemical/analysis; Water Pollutants, Chemical/isolation & purification*; Water Purification/methods*; Wetlands*; Waste Water/chemistry
  12. Distribution, mobility, and pollution assessment of Cd, Cu, Ni, Pb, Zn, and Fe in intertidal surface sediments of Sg. Puloh mangrove estuary, Malaysia
    Udechukwu BE, Ismail A, Zulkifli SZ, Omar H
    Environ Sci Pollut Res Int, 2015 Mar;22(6):4242-55.
    PMID: 25292304 DOI: 10.1007/s11356-014-3663-4
    Sungai Puloh mangrove estuary supports a large diversity of macrobenthic organisms and provides social benefits to the local community. Recently, it became a major recipient of heavy metals originating from industries in the hinterland as a result of industrialization and urbanization. This study was conducted to evaluate mobility and pollution status of heavy metals (Cd, Cu, Ni, Pb, Zn, and Fe) in intertidal surface sediments of this area. Surface sediment samples were collected based on four different anthropogenic sources. Metals concentrations were analyzed using an atomic absorption spectrophotometer (AAS). Results revealed that the mean concentrations were Zn (1023.68 ± 762.93 μg/g), Pb (78.8 ± 49.61 μg/g), Cu (46.89 ± 43.79 μg/g), Ni (35.54 ± 10.75 μg/g), Cd (0.94 ± 0.29 μg/g), and Fe (7.14 ± 0.94%). Most of the mean values of analyzed metals were below both the interim sediment quality guidelines (ISQG-low and ISQG-high), except for Pb concentration (above ISQG-low) and Zn concentration (above ISQG-high), thus suggesting that Pb and Zn may pose some environmental concern. Cadmium, Pb, and Zn concentrations were above the threshold effect level (TEL), indicating seldom adverse effect of these metals on macrobenthic organisms. Pollution load index (PLI) indicated deterioration and other indices revealed the intertidal surface sediment is moderately polluted with Cd, Pb, and Zn. Therefore, this mangrove area requires urgent attention to mitigate further contamination. Finally, this study will contribute to data sources for Malaysia in establishing her own ISQG since it is a baseline study with detailed contamination assessment indices for surface sediment of intertidal mangrove area.
    MeSH terms: Environmental Monitoring/methods*; Malaysia; Spectrophotometry, Atomic; Water Pollutants, Chemical/chemistry*; Water Pollution/analysis*; Geologic Sediments/chemistry*; Metals, Heavy/chemistry*; Estuaries*
  13. Endoscopic skull base training using 3D printed models with pre-existing pathology
    Narayanan V, Narayanan P, Rajagopalan R, Karuppiah R, Rahman ZA, Wormald PJ, et al.
    Eur Arch Otorhinolaryngol, 2015 Mar;272(3):753-7.
    PMID: 25294050 DOI: 10.1007/s00405-014-3300-3
    Endoscopic base of skull surgery has been growing in acceptance in the recent past due to improvements in visualisation and micro instrumentation as well as the surgical maturing of early endoscopic skull base practitioners. Unfortunately, these demanding procedures have a steep learning curve. A physical simulation that is able to reproduce the complex anatomy of the anterior skull base provides very useful means of learning the necessary skills in a safe and effective environment. This paper aims to assess the ease of learning endoscopic skull base exposure and drilling techniques using an anatomically accurate physical model with a pre-existing pathology (i.e., basilar invagination) created from actual patient data. Five models of a patient with platy-basia and basilar invagination were created from the original MRI and CT imaging data of a patient. The models were used as part of a training workshop for ENT surgeons with varying degrees of experience in endoscopic base of skull surgery, from trainees to experienced consultants. The surgeons were given a list of key steps to achieve in exposing and drilling the skull base using the simulation model. They were then asked to list the level of difficulty of learning these steps using the model. The participants found the models suitable for learning registration, navigation and skull base drilling techniques. All participants also found the deep structures to be accurately represented spatially as confirmed by the navigation system. These models allow structured simulation to be conducted in a workshop environment where surgeons and trainees can practice to perform complex procedures in a controlled fashion under the supervision of experts.
    MeSH terms: Endoscopy/education*; Humans; Models, Anatomic*; Otorhinolaryngologic Surgical Procedures/education; Skull Base/anatomy & histology*; Skull Base/surgery*; Neurosurgical Procedures/education; Printing, Three-Dimensional*
  14. Steroid-induced diabetes mellitus in systemic lupus erythematosus patients: analysis from a Malaysian multi-ethnic lupus cohort
    Shaharir SS, Gafor AH, Said MS, Kong NC
    Int J Rheum Dis, 2015 Jun;18(5):541-7.
    PMID: 25294584 DOI: 10.1111/1756-185X.12474
    OBJECTIVE:
    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease and glucocorticoid is the mainstay of treatment in SLE. The reported incidence of steroid-induced diabetes mellitus (SDM) ranged between 1-53%. We sought to investigate the prevalence and associated factors of SDM in patients with SLE.

    METHODOLOGY:
    A total of 100 SLE patients attending the Nephrology/SLE and Rheumatology Clinic, Universiti Kebangsaan Malaysia Medical Centre (UKMMC) who received corticosteroid treatment were recruited. The diagnosis of diabetes mellitus was based on the 2010 American Diabetes Association's criteria. Prevalent cases of SDM were also included. Statistical analysis was performed to determine the factors associated with SDM.

    RESULTS:
    Thirteen of them (13%) developed SDM, with the median onset of diagnosis from commencement of glucocorticoid treatment being 8 years (range 0.5-21 years). Although only seven Indians were recruited into the study, three of them (42.9%) had SDM compared to Malays (9.3%) and Chinese (12.8%) (P ≤ 0.05). Univariate and multivariate analysis showed that higher numbers of system or organ involvement in SLE, abdominal obesity, hypertriglyceridemia and daily prednisolone of ≥ 1 mg/kg/day were the important associated factors of SDM (P ≤ 0.05). Meanwhile, hydroxychloroquine (HCQ) use was associated with reduced SDM prevalence (P < 0.05).

    CONCLUSION:
    The prevalence of SDM among SLE patients was 13% and Indians were more prone to develop SDM compared to other races. Higher numbers of system involvement, abdominal obesity, hypertriglyceridemia and the use of oral prednisolone of ≥ 1 mg/kg/day were associated with SDM, while HCQ use potentially protects against SDM.

    © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

    KEYWORDS:
    SLE drug treatment; clinical aspects; systemic lupus erythematous
    MeSH terms: Adrenal Cortex Hormones/adverse effects*; Adrenal Cortex Hormones/therapeutic use*; Adult; China/ethnology; Cross-Sectional Studies; Diabetes Mellitus/chemically induced*; Diabetes Mellitus/epidemiology*; Diabetes Mellitus/prevention & control; Female; Humans; Hydroxychloroquine/therapeutic use; India/ethnology; Lupus Erythematosus, Systemic/drug therapy*; Lupus Erythematosus, Systemic/ethnology*; Lupus Erythematosus, Systemic/epidemiology; Malaysia/epidemiology; Male; Middle Aged; Prednisolone/adverse effects*; Prednisolone/therapeutic use*; Risk Factors; Hypertriglyceridemia/complications; Cohort Studies; Prevalence; Multivariate Analysis; Antirheumatic Agents/therapeutic use; Continental Population Groups; Obesity, Abdominal/complications
  15. Down-regulation of LPA receptor 5 contributes to aberrant LPA signalling in EBV-associated nasopharyngeal carcinoma
    Yap LF, Velapasamy S, Lee HM, Thavaraj S, Rajadurai P, Wei W, et al.
    J Pathol, 2015 Feb;235(3):456-65.
    PMID: 25294670 DOI: 10.1002/path.4460
    Undifferentiated nasopharyngeal carcinoma (NPC) is a highly metastatic disease that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the contribution of lysophosphatidic acid (LPA) signalling to the pathogenesis of NPC. Here we demonstrate two distinct functional roles for LPA in NPC. First, we show that LPA enhances the migration of NPC cells and second, that it can inhibit the activity of EBV-specific cytotoxic T cells. Focusing on the first of these phenotypes, we show that one of the LPA receptors, LPA receptor 5 (LPAR5), is down-regulated in primary NPC tissues and that this down-regulation promotes the LPA-induced migration of NPC cell lines. Furthermore, we found that EBV infection or ectopic expression of the EBV-encoded LMP2A was sufficient to down-regulate LPAR5 in NPC cell lines. Our data point to a central role for EBV in mediating the oncogenic effects of LPA in NPC and identify LPA signalling as a potential therapeutic target in this disease.
    MeSH terms: Adenocarcinoma/pathology; Adenocarcinoma/physiopathology; Carcinoma; Cell Movement/physiology; Herpesvirus 4, Human/physiology; Humans; Lysophospholipids/physiology*; Nasopharyngeal Neoplasms/pathology; Nasopharyngeal Neoplasms/physiopathology*; Phosphoric Diester Hydrolases/physiology; T-Lymphocytes, Cytotoxic/pathology; Viral Matrix Proteins/physiology; Signal Transduction/physiology*; Down-Regulation/physiology*; Gene Expression Regulation, Neoplastic/physiology*; Epstein-Barr Virus Infections/physiopathology*; Cell Line, Tumor; Receptors, Lysophosphatidic Acid/genetics; Receptors, Lysophosphatidic Acid/physiology*
  16. Goniothalamin enhances the ATPase activity of the molecular chaperone Hsp90 but inhibits its chaperone activity
    Yokoyama Y, Ohtaki A, Jantan I, Yohda M, Nakamoto H
    J. Biochem., 2015 Mar;157(3):161-8.
    PMID: 25294885 DOI: 10.1093/jb/mvu061
    Hsp90 is an ATP-dependent molecular chaperone that is involved in important cellular pathways such as signal transduction pathways. It is a potential cancer drug target because it plays a critical role for stabilization and activation of oncoproteins. Thus, small molecule compounds that control the Hsp90 function are useful to elucidate potential lead compounds against cancer. We studied effect of a naturally occurring styryl-lactone goniothalamin on the activity of Hsp90. Although many drugs targeting Hsp90 inhibit the ATPase activity of Hsp90, goniothalamin enhanced rather than inhibited the ATPase activity of a cyanobacterial Hsp90 (HtpG) and a yeast Hsp90. It increased both K(m) and k(cat) of the Hsp90s. Domain competition assays and tryptophan fluorescence measurements with various truncated derivatives of HtpG indicated that goniothalamin binds to the N-terminal domain of HtpG. Goniothalamin did not influence on the interaction of HtpG with a non-native protein or the anti-aggregation activity of HtpG significantly. However, it inhibited the activity of HtpG that assists refolding of a non-native protein in cooperation with the Hsp70 chaperone system. This is the first report to show that a small molecule that binds to the N-terminal domain of Hsp90 activates its ATPase activity, while inhibiting the chaperone function of Hsp90.
    MeSH terms: Adenosine Triphosphatases/chemistry; Adenosine Triphosphate/chemistry; Animals; Bacterial Proteins/chemistry*; Binding, Competitive; Glucosephosphate Dehydrogenase/chemistry; Hydrolysis; Kinetics; Pyrones/chemistry*; Rabbits; HSP90 Heat-Shock Proteins/chemistry*; Enzyme Activators/chemistry*; Synechococcus/enzymology; Protein Refolding
  17. Investigation of interaction studies of cefpirome with ACE-inhibitors in various buffers
    Nawaz M, Arayne MS, Sultana N, Abbas HF
    Spectrochim Acta A Mol Biomol Spectrosc, 2015 Feb 25;137:1050-4.
    PMID: 25300038 DOI: 10.1016/j.saa.2014.08.152
    This work describes a RP-HPLC method for the determination and interaction studies of cefpirome with ACE-inhibitors (captopril, enalapril and lisinopril) in various buffers. The separation and interaction of cefpirome with ACE-inhibitors was achieved on a Purospher Star, C18 (5 μm, 250×4.6 mm) column. Mobile phase consisted of methanol: water (80:20, v/v, pH 3.3); however, for the separation of lisinopril, it was modified to methanol-water (40:60, v/v, pH 3.3) and pumped at a flow rate of 1 mL min(-1). In all cases, UV detection was performed at 225 nm. Interactions were carried out in physiological pH i.e., pH 1 (simulated gastric juice), 4 (simulated full stomach), 7.4 (blood pH) and 9 (simulated GI), drug contents were analyzed by reverse phase high performance liquid chromatography. Method was found linear in the concentration range of 1.0-50.0 μg mL(-1) with correlation coefficient (r(2)) of 0.999. Precision (RSD%) was less than 2.0%, indicating good precision of the method and accuracy was 98.0-100.0%. Furthermore, cefpirome-ACE-inhibitors' complexes were also synthesized and results were elucidated on the basis of FT-IR, and (1)H NMR. The interaction results show that these interactions are pH dependent and for the co-administration of cefpirome and ACE-inhibitors, a proper interval should be given.
    MeSH terms: Angiotensin-Converting Enzyme Inhibitors/chemistry*; Buffers; Cephalosporins/chemistry*; Chromatography, High Pressure Liquid/methods; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy/methods; Spectroscopy, Fourier Transform Infrared/methods; Chromatography, Reverse-Phase/methods
  18. Fulltext Dietary intake of acrylamide and epithelial ovarian cancer risk in the european prospective investigation into cancer and nutrition (EPIC) cohort
    Obón-Santacana M, Peeters PH, Freisling H, Dossus L, Clavel-Chapelon F, Baglietto L, et al.
    Cancer Epidemiol Biomarkers Prev, 2015 Jan;24(1):291-7.
    PMID: 25300475 DOI: 10.1158/1055-9965.EPI-14-0636
    Acrylamide, classified in 1994 by the International Agency for Research on Cancer (IARC) as "probably carcinogenic" to humans, was discovered in 2002 in some heat-treated, carbohydrate-rich foods. The association between dietary acrylamide intake and epithelial ovarian cancer risk (EOC) has been previously studied in one case-control and three prospective cohort studies which obtained inconsistent results and could not further examine histologic subtypes other than serous EOC. The present study was carried out in the European Prospective Investigation into Cancer and Nutrition (EPIC) subcohort of women (n = 325,006). Multivariate Cox proportional hazards models were used to assess the association between questionnaire-based acrylamide intake and EOC risk. Acrylamide was energy-adjusted using the residual method and was evaluated both as a continuous variable (per 10 μg/d) and in quintiles; when subgroups by histologic EOC subtypes were analyzed, acrylamide intake was evaluated in quartiles. During a mean follow-up of 11 years, 1,191 incident EOC cases were diagnosed. At baseline, the median acrylamide intake in EPIC was 21.3 μg/d. No associations and no evidence for a dose-response were observed between energy-adjusted acrylamide intake and EOC risk (HR10μg/d,1.02; 95% CI, 0.96-1.09; HRQ5vsQ1, 0.97; 95% CI, 0.76-1.23). No differences were seen when invasive EOC subtypes (582 serous, 118 endometrioid, and 79 mucinous tumors) were analyzed separately. This study did not provide evidence that acrylamide intake, based on food intake questionnaires, was associated with risk for EOC in EPIC. Additional studies with more reliable estimates of exposure based on biomarkers may be needed.
    MeSH terms: Europe; Humans; Middle Aged; Neoplasms, Glandular and Epithelial/etiology*; Ovarian Neoplasms/etiology*; Prospective Studies; Risk Factors; Cohort Studies; Nutrition Assessment; Acrylamide/adverse effects*
  19. Biochemical properties of xylose reductase prepared from adapted strain of Candida tropicalis
    Rafiqul IS, Sakinah AM
    Appl Biochem Biotechnol, 2015 Jan;175(1):387-99.
    PMID: 25300602 DOI: 10.1007/s12010-014-1269-4
    Xylose reductase (XR) is an intracellular enzyme, which catalyzes xylose to xylitol conversion in the microbes. It has potential biotechnological applications in the manufacture of various commercially important specialty bioproducts including xylitol. This study aimed to prepare XR from adapted strain of Candida tropicalis and to characterize it. The XR was isolated from adapted C. tropicalis, cultivated on Meranti wood sawdust hemicellulosic hydrolysate (MWSHH)-based medium, via ultrasonication, and was characterized based on enzyme activity, stability, and kinetic parameters. It was specific to NADPH with an activity of 11.16 U/mL. The enzyme was stable at pH 5-7 and temperature of 25-40 °C for 24 h and retained above 95 % of its original activity after 4 months of storage at -80 °C. The K m of XR for xylose and NADPH were 81.78 mM and 7.29 μM while the V max for them were 178.57 and 12.5 μM/min, respectively. The high V max and low K m values of XR for xylose reflect a highly productive reaction among XR and xylose. MWSHH can be a promising xylose source for XR preparation from yeast.
    MeSH terms: Aldehyde Reductase/genetics; Aldehyde Reductase/isolation & purification; Aldehyde Reductase/chemistry*; Fermentation; Hydrogen-Ion Concentration; Kinetics; Temperature; Xylitol/biosynthesis; Candida tropicalis/enzymology*
  20. Fulltext Prolonged clinical course of muscular sarcocystosis and effectiveness of cotrimoxazole among travelers to Tioman Island, Malaysia, 2011-2014
    Slesak G, Schäfer J, Langeheinecke A, Tappe D
    Clin Infect Dis, 2015 Jan 15;60(2):329.
    PMID: 25301217 DOI: 10.1093/cid/ciu791
    MeSH terms: Female; Humans; Male; Sarcocystosis/epidemiology*; Travel*; Islands*
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