Browse publications by year: 2016

  1. Ong GH, Wong LS, Tan AL, Yap CK
    Environ Monit Assess, 2016 Jan;188(1):40.
    PMID: 26687083 DOI: 10.1007/s10661-015-5042-0
    Centella asiatica is a commonly used medicinal plant in Malaysia. As heavy metal accumulation in medicinal plants which are highly consumed by human is a serious issue, thus the assessment of heavy metals in C. asiatica is important for the safety of consumers. In this study, the heavy metal accumulation in C. asiatica and the potential health risks were investigated. Samples of C. asiatica and surface soils were collected from nine different sites around Peninsular Malaysia. The concentration of six heavy metals namely Cd, Cu, Ni, Fe, Pb and Zn were determined by air-acetylene flame atomic absorption spectrophotometer (AAS). The degree of anthropogenic influence was assessed by calculating the enrichment factor (EF) and index of geoaccumulation (Igeo). The heavy metal uptake into the plant was estimated through the calculation of translocation factor (TF), bioconcentration factor (BCF) and correlation study. Estimated daily intakes (EDI) and target hazard quotients (THQ) were used to determine the potential health risk of consuming C. asiatica. The results showed that the overall surface soil was polluted by Cd, Cu and Pb, while the uptake of Zn and Ni by the plants was high. The value of EDI and THQ showed that the potential of Pb toxicity in C. asiatica was high as well. As heavy metal accumulation was confirmed in C. asiatica, daily consumption of the plant derived from polluted sites in Malaysia was not recommended.
    MeSH terms: Environmental Monitoring*; Environmental Pollution/statistics & numerical data; Humans; Malaysia; Risk; Soil; Soil Pollutants/analysis*; Metals, Heavy/analysis*; Centella/chemistry*
  2. Rajahram GS, Barber BE, William T, Grigg MJ, Menon J, Yeo TW, et al.
    Emerg Infect Dis, 2016 Jan;22(1):41-8.
    PMID: 26690736 DOI: 10.3201/eid2201.151305
    Deaths from Plasmodium knowlesi malaria have been linked to delayed parenteral treatment. In Malaysia, early intravenous artesunate is now recommended for all severe malaria cases. We describe P. knowlesi fatalities in Sabah, Malaysia, during 2012-2014 and report species-specific fatality rates based on 2010-2014 case notifications. Sixteen malaria-associated deaths (caused by PCR-confirmed P. knowlesi [7], P. falciparum [7], and P. vivax [1] and microscopy-diagnosed "P. malariae" [1]) were reported during 2012-2014. Six patients with severe P. knowlesi malaria received intravenous artesunate at hospital admission. For persons ≥15 years of age, overall fatality rates during 2010-2014 were 3.4, 4.2, and 1.0 deaths/1,000 P. knowlesi, P. falciparum, and P. vivax notifications, respectively; P. knowlesi-associated fatality rates fell from 9.2 to 1.6 deaths/1,000 notifications. No P. knowlesi-associated deaths occurred among children, despite 373 notified cases. Although P. knowlesi malaria incidence is rising, the notification-fatality rate has decreased, likely due to improved use of intravenous artesunate.
    MeSH terms: Adult; Aged; Female; Humans; Malaria/mortality*; Malaria/epidemiology*; Malaysia/epidemiology; Male; Middle Aged; Incidence; Plasmodium knowlesi/pathogenicity*
  3. Teoh Bing Fei J, Yee A, Habil MH
    Am J Addict, 2016 Jan;25(1):49-55.
    PMID: 26692463 DOI: 10.1111/ajad.12317
    BACKGROUND AND OBJECTIVES: Co-occurring psychiatric disorders are among the difficulties faced by patients with opioid dependence on methadone maintenance therapy (MMT). This study aims to assess the prevalence of psychiatric comorbidity among patients on MMT, the factors predicting psychiatric comorbidity and to examine the association between psychiatric comorbidity and quality of life.
    METHODS: A total of 225 male patients on MMT in a tertiary hospital in Malaysia were assessed for psychiatric comorbidity and substance use disorders using the Mini-International Neuropsychiatric Interview (MINI) and Opiate Treatment Index (OTI). Their quality of life was assessed using World Health Organization Quality of Life (WHOQOL)-BREF.
    RESULTS: The prevalence of a current and lifetime non-substance use Axis I psychiatric disorder was 14.2% and 15.6% respectively, while 14.7% fulfilled the criteria for antisocial personality disorder. 80.9% had comorbid substance dependence, predominantly nicotine dependence. Factors significantly associated with a non-substance use Axis I psychiatric disorder on multivariate analysis were use of psychiatric medications, antisocial personality disorder and poorer physical health. Patients with a non-substance use Axis I psychiatric disorder had a significantly poorer quality of life in all domains namely physical health, psychological, social relationships, environment as well as combined quality of life and general health after controlling for possible confounders.
    CONCLUSION: Psychiatric comorbidity among patients on MMT negatively impacts quality of life.
    SCIENTIFIC SIGNIFICANCE: The detection of psychiatric disorders and provision of appropriate treatment is needed to improve the quality of life of patients on MMT.
    MeSH terms: Adult; Analgesics, Opioid/therapeutic use; Antisocial Personality Disorder/epidemiology; Mental Disorders/epidemiology*; Humans; Malaysia/epidemiology; Male; Methadone/therapeutic use*; Opioid-Related Disorders/drug therapy*; Opioid-Related Disorders/epidemiology*; Opioid-Related Disorders/psychology; Quality of Life/psychology*; Risk Factors; Comorbidity; Prevalence; Opiate Substitution Treatment/psychology*
  4. Yong GY, Pan SW, Humayun Akhter F, Law TN, Toh TH
    PMID: 26693590 DOI: 10.1097/APO.0000000000000150
    PURPOSE: To study the demographic characteristics of ocular trauma in Central Sarawak and identify the determinant factors of poor visual outcome.

    DESIGN: A retrospective study of ocular trauma cases presenting at the referral hospital in 2013.

    METHODS: Patients were identified and recruited from hospital records. Those presenting for follow-up review were excluded. Case records were retrieved and reviewed after recruitment.

    RESULTS: We studied 168 patients with 179 ocular injuries, of which 44% were work related. Compared with non-work-related cases, work-related cases were more likely to be male [odds ratio (OR), 19.7; 95% confidence interval (CI), 2.6-150.9] and foreign (OR, 18.0; 95% CI, 2.3-142.0). Open globe injuries constituted a higher percentage of impaired visual acuity (VA) during the first visit: 84.6% compared with 18.1% for closed globe injuries (OR, 25.0; 95% CI, 5.3-118.4; P < 0.001). Of the open globe injuries, 61.5% worsened or showed no improvement in VA after 3 months compared with closed globe injuries (28.9%) (OR, 3.9; 95% CI, 1.2-12.7; P = 0.015). Of cases presenting 7 or more days after trauma, 76.9% worsened or showed no improvement in VA after 3 months compared with those presenting in less than 7 days (27.7%) (OR, 8.7; 95% CI, 2.3-33.0; P < 0.001). Among those with work-related injuries, 23.1% had used eye protective devices (EPDs).

    CONCLUSIONS: Ocular injuries in Central Sarawak were predominantly work related, occurring at industrial premises, and involving males and foreigners. Both open globe injuries and a delay in seeking treatment resulted in significantly poorer visual outcomes.

    MeSH terms: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Eye Injuries/etiology; Eye Injuries/epidemiology*; Eye Injuries/physiopathology; Female; Humans; Malaysia/epidemiology; Male; Middle Aged; Prognosis; Retrospective Studies; Visual Acuity/physiology; Trauma Severity Indices; Odds Ratio; Young Adult; Occupational Injuries/epidemiology
  5. Mahakkanukrauh P, Das S
    Anat Sci Int, 2016 Mar;91(2):215.
    PMID: 26694711 DOI: 10.1007/s12565-015-0321-y
    MeSH terms: Circle of Willis/anatomy & histology*; Circle of Willis/physiology*; Humans
  6. Pramanik BK, Pramanik SK, Suja F
    Environ Technol, 2016 Aug;37(15):1857-64.
    PMID: 26695189 DOI: 10.1080/09593330.2015.1134677
    The impact of biological activated carbon (BAC), sand filtration (SF) and biological aerated filter (BAF) for removal of the selected organic micropollutants and polyfluoroalkyl substances (PFASs) from secondary effluent was studied. BAC led to greater removal of dissolved organic carbon (43%) than BAF (30%) which in turn was greater than SF (24%). All biological filtration systems could effectively remove most of the selected organic micropollutants, and there was a greater removal of these micropollutants by BAC (76-98%) than BAF (70-92%) or SF (68-90%). It was found that all treatment was effective for removal of the hydrophobic (log D > 3.2) and readily biodegradable organic micropollutants. The major mechanism for the removal of these molecules was biodegradation by the micro-organism and sorption by the biofilm. Compared to organic micropollutants removal, there was a lower removal of PFASs by all treatments, and BAF and SF had a considerably lower removal than BAC treatment. The better removal for all molecule types by BAC was due to additional adsorption capacity by the activated carbon. This study demonstrated that the BAC process was most effective in removing organic micropollutants present in the secondary effluent.
    MeSH terms: Biodegradation, Environmental*; Filtration/methods*; Hydrocarbons, Fluorinated/analysis; Hydrocarbons, Fluorinated/isolation & purification*; Hydrocarbons, Fluorinated/chemistry; Water Pollutants, Chemical/analysis; Water Pollutants, Chemical/isolation & purification*; Water Pollutants, Chemical/chemistry; Biofilms; Bioreactors/microbiology*; Hydrophobic and Hydrophilic Interactions
  7. Saedon NI, Zainal-Abidin I, Chee KH, Khor HM, Tan KM, Kamaruzzaman SK, et al.
    Clin Auton Res, 2016 Feb;26(1):41-8.
    PMID: 26695401 DOI: 10.1007/s10286-015-0327-5
    To determine the magnitude of postural blood pressure change, differences in ECG between fallers and non-fallers were measured. Postural blood pressure change is associated with symptoms of dizziness, presyncope, and syncope.
    MeSH terms: Accidental Falls*; Aged; Blood Pressure/physiology*; Cross-Sectional Studies; Dizziness/etiology; Dizziness/physiopathology*; Electrocardiography; Female; Humans; Hypotension, Orthostatic/complications; Hypotension, Orthostatic/physiopathology*; Male; Posture; Syncope/etiology; Syncope/physiopathology*
  8. Nawaz A, Wong TW
    J Microsc, 2016 07;263(1):34-42.
    PMID: 26695532 DOI: 10.1111/jmi.12371
    The chitosan has been used as the primary excipient in transdermal particulate dosage form design. Its distribution pattern across the epidermis and dermis is not easily accessible through chemical assay and limited to radiolabelled molecules via quantitative autoradiography. This study explored Fourier-transform infrared spectroscopy imaging technique with built-in microscope as the means to examine chitosan molecular distribution over epidermis and dermis with the aid of histology operation. Fourier-transform infrared spectroscopy skin imaging was conducted using chitosan of varying molecular weights, deacetylation degrees, particle sizes and zeta potentials, obtained via microwave ligation of polymer chains at solution state. Both skin permeation and retention characteristics of chitosan increased with the use of smaller chitosan molecules with reduced acetyl content and size, and increased positive charge density. The ratio of epidermal to dermal chitosan content decreased with the use of these chitosan molecules as their accumulation in dermis (3.90% to 18.22%) was raised to a greater extent than epidermis (0.62% to 1.92%). A larger dermal chitosan accumulation nonetheless did not promote the transdermal polymer passage more than the epidermal chitosan. A small increase in epidermal chitosan content apparently could fluidize the stratum corneum and was more essential to dictate molecular permeation into dermis and systemic circulation. The histology technique aided Fourier-transform infrared spectroscopy imaging approach introduces a new dimension to the mechanistic aspect of chitosan in transdermal delivery.
    MeSH terms: Administration, Cutaneous; Animals; Histological Techniques/methods*; Male; Molecular Weight; Skin/metabolism; Skin/chemistry*; Spectroscopy, Fourier Transform Infrared/methods*; Chitosan/administration & dosage*; Chitosan/analysis*; Chitosan/pharmacokinetics; Chitosan/chemistry; Rats
  9. Underwood AP, Kaakoush NO, Sodhi N, Merif J, Seah Lee W, Riordan SM, et al.
    J Med Microbiol, 2016 Mar;65(3):219-226.
    PMID: 26698172 DOI: 10.1099/jmm.0.000216
    Given that Campylobacter jejuni is recognized as the most common cause of bacterial gastroenteritis worldwide, recent findings showing comparable levels of Campylobacter concisus in patients with gastroenteritis would suggest that this bacterium is clinically important. The prevalence and abundance of Campylobacter concisus in stool samples collected from patients with acute gastroenteritis was examined using quantitative real-time PCR. The associated virulence determinants exotoxin 9 and zonula occludens toxin DNA were detected for Campylobacter concisus-infected samples using real-time PCR. Campylobacter concisus was detected at high prevalence in patients with gastroenteritis (49.7 %), higher than that observed for Campylobacter jejuni (∼5 %). The levels of Campylobacter concisus were putatively classified into clinically relevant and potentially transient subgroups based on a threshold developed using Campylobacter jejuni levels, as the highly sensitive real-time PCR probably detected transient passage of the bacterium from the oral cavity. A total of 18 % of patients were found to have clinically relevant levels of Campylobacter concisus, a significant number of which also had high levels of one of the virulence determinants. Of these patients, 78 % were found to have no other gastrointestinal pathogen identified in the stool, which strongly suggests a role for Campylobacter concisus in the aetiology of gastroenteritis in these patients. These results emphasize the need for diagnostic laboratories to employ identification protocols for emerging Campylobacter species. Clinical follow-up in patients presenting with high levels of Campylobacter concisus in the intestinal tract is needed, given that it has been associated with more chronic sequelae.
    MeSH terms: Adolescent; Adult; Campylobacter/classification*; Campylobacter/pathogenicity*; Campylobacter Infections/microbiology*; Child; Child, Preschool; Diarrhea/microbiology; Feces/microbiology; Female; Gastroenteritis/microbiology*; Humans; Infant; Male; Middle Aged; Virulence; Gene Expression Regulation, Bacterial/physiology; Young Adult
  10. Lo TS, Pue LB, Tan YL, Wu PY
    Int Urogynecol J, 2016 Jun;27(6):923-31.
    PMID: 26700103 DOI: 10.1007/s00192-015-2912-5
    INTRODUCTION AND HYPOTHESIS: To study the outcomes following repeat midurethral sling (MUS) surgery in patients with persistent or recurrent stress urinary incontinence after failure of primary MUS surgery and risk factors for surgical failure.

    METHODS: The medical records of 24 patients who underwent repeat MUS surgery at a single tertiary center from January 2004 to February 2014 were reviewed. The types of MUS used for the repeat surgey were transobturator, retropubic and single incision slings. Objective cure was defined as no demonstrable involuntary leakage of urine during increased abdominal pressure in the absence of a detrusor contraction observed during filling cystometry, and subjective cure was defined as a negative response to Urogenital Distress Inventory six (UDI-6) question 3 during follow-up between 6 months and 1 year postoperatively. The change in the inclination angle between the urethra and pubic axis was measured with introital ultrasonography and the cotton swab test performed.

    RESULTS: The objective and subjective cure rates were 79.2 % and 75 %, respectively. There were no differences in demographics between the patients with failure of surgery and those with successful surgery. Significant independent risk factors for failure of repeat MUS surgery were a change in cotton swab angle at rest and straining of <30° (OR 4.6, 95 % CI 2.5 - 7.9°), a change in inclination angle of <30° (OR 4.6, 95 % CI 2.5 - 7.9°), intrinsic sphincter deficiency (OR 3.4, 95 % CI 1.8 - 6.1) and a mean urethral closure pressure of <60 cm H2O (OR 2.9, 95 % CI 1.5 - 4.5). In one patient the bladder was perforated.

    CONCLUSIONS: Repeat MUS surgery is safe and has a good short-term success rate, both objectively and subjectively, with independent risk factors for failure related to bladder neck hypomobility and poor urethral function.

    MeSH terms: Adult; Aged; Female; Humans; Middle Aged; Recurrence; Reoperation/statistics & numerical data*; Retrospective Studies; Risk Factors; Gynecologic Surgical Procedures/statistics & numerical data*; Ultrasonography; Urinary Incontinence, Stress/surgery*; Treatment Failure; Suburethral Slings*
  11. Raghavendran HR, Mohan S, Genasan K, Murali MR, Naveen SV, Talebian S, et al.
    Colloids Surf B Biointerfaces, 2016 Mar 1;139:68-78.
    PMID: 26700235 DOI: 10.1016/j.colsurfb.2015.11.053
    Scaffolds with structural features similar to the extracellular matrix stimulate rapid osteogenic differentiation in favorable microenvironment and with growth factor supplementation. In this study, the osteogenic potential of electrospun poly-l-lactide/hydroxyapatite/collagen (PLLA/Col/HA, PLLA/HA and PLLA/Col) scaffolds were tested in vitro with the supplementation of platelet derived growth factor-BB (PDGF-BB). Cell attachment and topography, mineralization, extracellular matrix protein localization, and gene expression of the human mesenchymal stromal cells were compared between the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA. The levels of osteocalcin, calcium, and mineralization were significantly greater in the PLLA/Col/HA and PLLA/HA compared with PLLA/Col. High expression of fibronectin, intracellular adhesion molecule, cadherin, and collagen 1 (Col1) suggests that PLLA/Col/HA and PLLA/HA scaffolds had superior osteoinductivity than PLLA/Col. Additionally, osteopontin, osteocalcin, osterix, Runt-related transcription factor 2 (Runx2), and bone morphogenic protein (BMP2) expression were higher in PLLA/Col/HA and PLLA/HA compared with PLLA/Col. In comparison with PLLA/Col, the PLLA/Col/HA and PLLA/HA scaffolds presented a significant upregulation of the genes Runx2, Col 1, Integrin, osteonectin (ON), bone gamma-carboxyglutamic acid-containing protein (BGALP), osteopontin (OPN), and BMP2. The upregulation of these genes was further increased with PDGF-BB supplementation. These results show that PDGF-BB acts synergistically with PLLA/Col/HA and PLLA/HA to enhance the osteogenic differentiation potential. Therefore, this combination can be used for the rapid expansion of bone marrow stromal cells into bone-forming cells for tissue engineering.
    MeSH terms: Bone Marrow Cells/cytology; Bone Marrow Cells/drug effects; Bone Marrow Cells/metabolism; Calcification, Physiologic/drug effects; Cell Differentiation/drug effects; Fibronectins/genetics; Fibronectins/metabolism; Humans; Osteoblasts/cytology; Osteoblasts/drug effects*; Osteoblasts/metabolism; Osteogenesis/drug effects; Polyesters/pharmacology*; Polyesters/chemistry; Transcription Factors/genetics; Transcription Factors/metabolism; Biomarkers/metabolism; Osteocalcin/genetics; Osteocalcin/metabolism; Gene Expression; Durapatite/pharmacology*; Durapatite/chemistry; Proto-Oncogene Proteins c-sis/pharmacology*; Tissue Engineering; Collagen Type I/genetics; Collagen Type I/metabolism; Collagen Type I/pharmacology*; Core Binding Factor Alpha 1 Subunit/genetics; Core Binding Factor Alpha 1 Subunit/metabolism; Osteopontin/genetics; Osteopontin/metabolism; Tissue Scaffolds; Bone Morphogenetic Protein 2/genetics; Bone Morphogenetic Protein 2/metabolism; Mesenchymal Stromal Cells/cytology; Mesenchymal Stromal Cells/drug effects*; Mesenchymal Stromal Cells/metabolism; Primary Cell Culture
  12. Choi JR, Hu J, Feng S, Wan Abas WA, Pingguan-Murphy B, Xu F
    Biosens Bioelectron, 2016 May 15;79:98-107.
    PMID: 26700582 DOI: 10.1016/j.bios.2015.12.005
    Lateral flow assays (LFAs) have currently attracted broad interest for point-of-care (POC) diagnostics, but their application has been restricted by poor quantification and limited sensitivity. While the former has been currently solved to some extent by the development of handheld or smartphone-based readers, the latter has not been addressed fully, particularly the potential influences of environmental conditions (e.g., temperature and relative humidity (RH)), which have not yet received serious attention. The present study reports the use of a portable temperature-humidity control device to provide an optimum environmental requirement for sensitivity improvement in LFAs, followed by quantification by using a smartphone. We found that a RH beyond 60% with temperatures of 55-60°C and 37-40°C produced optimum nucleic acid hybridization and antigen-antibody interaction in LFAs, respectively representing a 10-fold and 3-fold signal enhancement over ambient conditions (25°C, 60% RH). We envision that in the future the portable device could be coupled with a fully integrated paper-based sample-to-answer biosensor for sensitive detection of various target analytes in POC settings.
  13. Huang L, Luo X, Shao J, Yan H, Qiu Y, Ke P, et al.
    Eur J Clin Microbiol Infect Dis, 2016 Feb;35(2):269-77.
    PMID: 26700953 DOI: 10.1007/s10096-015-2540-5
    Dengue is a rapidly spreading mosquito-borne disease caused by the dengue virus (DENV) and has emerged as a severe public health problem around the world. Guangdong, one of the southern Chinese provinces, experienced a serious outbreak of dengue in 2014, which was believed to be the worst dengue epidemic in China over the last 20 years. To better understand the epidemic, we collected the epidemiological data of the outbreak and analyzed 14,594 clinically suspected dengue patients from 25 hospitals in Guangdong. Dengue cases were then laboratory-confirmed by the detection of DENV non-structural protein 1 (NS1) antigen and/or DENV RNA. Afterwards, clinical manifestations of dengue patients were analyzed and 93 laboratory-positive serum specimens were chosen for the DENV serotyping and molecular analysis. Our data showed that the 2014 dengue outbreak in Guangdong had spread to 20 cities and more than 45 thousand people suffered from dengue fever. Of 14,594 participants, 11,387 were definitively diagnosed. Most manifested with a typical non-severe clinical course, and 1.96 % developed to severe dengue. The strains isolated successfully from the serum samples were identified as DENV-1. Genetic analyses revealed that the strains were classified into genotypes I and V of DENV-1, and the dengue epidemic of Guangdong in 2014 was caused by indigenous cases and imported cases from the neighboring Southeast Asian countries of Malaysia and Singapore. Overall, our study is informative and significant to the 2014 dengue outbreak in Guangdong and will provide crucial implications for dengue prevention and control in China and elsewhere.
    MeSH terms: Animals; China; Cities; Dengue Virus; Disease Outbreaks; Genotype; Humans; Malaysia; Culicidae; Public Health; RNA; Serotyping; Singapore; Severe Dengue; Epidemics
  14. Lin YK, Show PL, Yap YJ, Ariff AB, Mohammad Annuar MS, Lai OM, et al.
    J Biosci Bioeng, 2016 Jun;121(6):692-696.
    PMID: 26702953 DOI: 10.1016/j.jbiosc.2015.11.001
    Aqueous two-phase system (ATPS) extractive bioconversion provides a technique which integrates bioconversion and purification into a single step process. Extractive bioconversion of gamma-cyclodextrin (γ-CD) from soluble starch with cyclodextrin glycosyltransferase (CGTase, EC 2.4.1.19) enzyme derived from Bacillus cereus was evaluated using polyethylene glycol (PEG)/potassium phosphate based on ATPS. The optimum condition was attained in the ATPS constituted of 30.0% (w/w) PEG 3000 g/mol and 7.0% (w/w) potassium phosphate. A γ-CD concentration of 1.60 mg/mL with a 19% concentration ratio was recovered after 1 h bioconversion process. The γ-CD was mainly partitioned to the top phase (YT=81.88%), with CGTase partitioning in the salt-rich bottom phase (KCGTase=0.51). Repetitive batch processes of extractive bioconversion were successfully recycled three times, indicating that this is an environmental friendly and a cost saving technique for γ-CD production and purification.
    MeSH terms: Bacillus cereus/enzymology*; Glucosyltransferases/metabolism*; Phosphates/chemistry*; Polyethylene Glycols/chemistry*; Starch/metabolism; Starch/chemistry; Water/chemistry*; Potassium Compounds/chemistry*; gamma-Cyclodextrins/isolation & purification*; gamma-Cyclodextrins/metabolism*
  15. Yusuf M, Mohamed N, Mohamad S, Janezic D, Damodaran KV, Wahab HA
    J Chem Inf Model, 2016 Jan 25;56(1):82-100.
    PMID: 26703840 DOI: 10.1021/acs.jcim.5b00331
    Increased reports of oseltamivir (OTV)-resistant strains of the influenza virus, such as the H274Y mutation on its neuraminidase (NA), have created some cause for concern. Many studies have been conducted in the attempt to uncover the mechanism of OTV resistance in H274Y NA. However, most of the reported studies on H274Y focused only on the drug-bound system, so the direct effects of the mutation on NA itself prior to drug binding still remain unclear. Therefore, molecular dynamics simulations of NA in apo form, followed by principal component analysis and interaction energy calculations, were performed to investigate the structural changes of the NA binding site as a result of the H274Y mutation. It was observed that the disruption of the NA binding site due to the H274Y mutation was initiated by the repulsive effect of Y274 on the 250-loop, which in turn altered the hydrogen-bonding network around residue 274. The rotated W295 side chain caused the upward movement of the 340-loop. Consequently, sliding box docking results suggested that the binding pathway of OTV was compromised because of the disruption of this binding site. This study also highlighted the importance of the functional group at C6 of the sialic acid mimicry. It is hoped that these results will improve the understanding of OTV resistance and shed some light on the design of a novel anti-influenza drug.
    MeSH terms: Antiviral Agents/metabolism; Antiviral Agents/pharmacology; Binding Sites; Histidine; Hydrogen Bonding; Mutation*; Neuraminidase/genetics*; Neuraminidase/metabolism*; Neuraminidase/chemistry; Protein Conformation; Drug Resistance, Viral/genetics*; Influenza A Virus, H5N1 Subtype/drug effects; Influenza A Virus, H5N1 Subtype/enzymology; Oseltamivir/metabolism*; Oseltamivir/pharmacology*; Zanamivir/metabolism; Molecular Dynamics Simulation*
  16. Adam SH, Giribabu N, Rao PV, Sayem AS, Arya A, Panichayupakaranant P, et al.
    Eur J Pharmacol, 2016 Jan 15;771:173-90.
    PMID: 26703866 DOI: 10.1016/j.ejphar.2015.12.028
    Effect of Rhinacanthin C on hyperglycaemia, hyperlipidemia and pancreatic dysfunction in diabetes was investigated. In-vitro effect of Rhinacanthin C on glucose uptake was studied in 3T3-L1 cell line. Meanwhile, in-vivo effect of 28-days treatment with 5mg/kg/day or 20mg/kg/day Rhinacanthin C was studied in streptozotocin-nicotinamide induced male diabetic rats. Following completion of treatment, fasting blood glucose (FBG), HbA1c, insulin and lipid profile levels were measured by biochemical assays. Histopathological changes in pancreas were observed by light microscopy while levels of pancreatic oxidative stress were determined by enzymatic assays. Expression of insulin, TNFα, Ikkβ and caspase-3 in pancreas were quantified by immunohistochemistry. Molecular docking was used to identify interactions between Rhinacathin C with SOD or GPx enzymes. Dose-dependent increase in glucose uptake was observed with increasing doses of Rhinacathin C. Plasma FBG, HbA1c and lipid profile except LDL levels and pancreatic malonaldehyde level were reduced but serum insulin and pancreatic anti-oxidative enzymes (SOD, CAT and GPx) levels were increased in diabetic rats receiving Rhinacanthin C treatment. Decreased pancreatic histopathological changes with higher pancreatic insulin and Glut-2 levels but lower TNFα, Ikkβ and caspase-3 levels were observed in diabetic rats receiving Rhinacanthin C (P<0.05 compared to non-treated diabetic rats). In diabetic rats which received Rhinacathin C, changes in the above parameters did not achieve the value in non-diabetic rats. Docking shows Rhinacathin C possesses high degree interactions with SOD and GPx. By possessing these effects, Rhinacanthin C could be used as agent to alleviate pancreatic and other complications in diabetes.
    MeSH terms: Animals; Antioxidants/metabolism; Blood Glucose/analysis; Blood Glucose/metabolism; Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/pathology*; Dose-Response Relationship, Drug; Hemoglobin A, Glycosylated/analysis; Hemoglobin A, Glycosylated/metabolism; Hyperglycemia/blood; Hyperglycemia/drug therapy*; Hyperlipidemias/blood; Hyperlipidemias/drug therapy*; Hypoglycemic Agents/therapeutic use*; Insulin/metabolism; Lipids/blood; Male; Naphthoquinones/therapeutic use*; Niacinamide; Pancreas/metabolism; Pancreas/pathology*; Streptozocin; Rats, Sprague-Dawley; Rats
  17. Tan JM, Karthivashan G, Abd Gani S, Fakurazi S, Hussein MZ
    J Mater Sci Mater Med, 2016 Feb;27(2):26.
    PMID: 26704543 DOI: 10.1007/s10856-015-5635-8
    Chemically functionalized carbon nanotubes are highly suitable and promising materials for potential biomedical applications like drug delivery due to their distinct physico-chemical characteristics and unique architecture. However, they are often associated with problems like insoluble in physiological environment and cytotoxicity issue due to impurities and catalyst residues contained in the nanotubes. On the other hand, surface coating agents play an essential role in preventing the nanoparticles from excessive agglomeration as well as providing good water dispersibility by replacing the hydrophobic surfaces of nanoparticles with hydrophilic moieties. Therefore, we have prepared four types of biopolymer-coated single walled carbon nanotubes systems functionalized with anticancer drug, betulinic acid in the presence of Tween 20, Tween 80, polyethylene glycol and chitosan as a comparative study. The Fourier transform infrared spectroscopy studies confirm the bonding of the coating molecules with the SWBA and these results were further supported by Raman spectroscopy. All chemically coated samples were found to release the drug in a slow, sustained and prolonged fashion compared to the uncoated ones, with the best fit to pseudo-second order kinetic model. The cytotoxic effects of the synthesized samples were evaluated in mouse embryonic fibroblast cells (3T3) at 24, 48 and 72 h. The in vitro results reveal that the cytotoxicity of the samples were dependent upon the drug release profiles as well as the chemical components of the surface coating agents. In general, the initial burst, drug release pattern and cytotoxicity could be well-controlled by carefully selecting the desired materials to suit different therapeutic applications.
    MeSH terms: Animals; Antineoplastic Agents/pharmacokinetics; Antineoplastic Agents/chemistry*; Cell Survival/drug effects; Cells, Cultured; Drug Carriers/chemical synthesis; Drug Carriers/pharmacokinetics; Drug Carriers/chemistry; Materials Testing; Polyethylene Glycols/chemistry; Polymers/chemical synthesis; Polymers/pharmacokinetics; Polymers/chemistry; Triterpenes/pharmacokinetics; Triterpenes/chemistry*; Drug Delivery Systems*; Nanotubes, Carbon/chemistry*; Chitosan/chemistry; Mice; Hydrophobic and Hydrophilic Interactions
  18. BangaSingh KK, Nisha M, Lau HY, Ravichandran M, Salleh MZ
    Microb Pathog, 2016 Feb;91:123-8.
    PMID: 26706344 DOI: 10.1016/j.micpath.2015.12.004
    Virulence of Shigella is attributed to the genes presence in chromosome or in the megaplasmid. The apy gene which is located in the megaplasmid of Shigella species encodes for apyrase enzyme, a pathogenesis-associated enzyme causing mitochondrial damage and host cell death. In this study we constructed an apy mutant of Shigella flexneri by insertional activation using a kanamycin resistant gene cassette. The wild type apy gene of S. flexneri 2a was PCR amplified, cloned and mutated with insertion of kanamycin resistant gene cassette (aphA). The mutated construct (apy: aphA) was subcloned into a conjugative suicidal vector (pWM91) at the unique Sma1 and Sac1 sites. The mutation of the wild apy gene in the construct was confirmed by DNA sequencing. The mutated construct was introduced into wild type S. flexneri 2a by conjugation with Escherichia coli. After undergoing homologous recombination, the wild apy gene was deleted from the construct using the sucrose selection method. Non-functional activity of the apyrase enzyme in the constructed strain by colorimetric test indicated the successful mutation of the apyrase enzyme. This strain with mutated apy gene was evaluated for its protective efficacy using the guinea pig keratoconjunctivitis model. The strain was Sereny negative and it elicited a significant protection following challenge with wild S. flexneri strain. This apy mutant strain will form a base for the development of a vaccine target for shigellosis.
    MeSH terms: Animals; Apyrase/genetics; Apyrase/metabolism*; Bacterial Proteins/genetics; Bacterial Proteins/metabolism*; Dysentery, Bacillary/microbiology*; Guinea Pigs; Humans; Mutation; Shigella flexneri/enzymology*; Shigella flexneri/genetics; Shigella flexneri/pathogenicity*; Virulence
  19. Chung EL, Abdullah FF, Ibrahim HH, Marza AD, Zamri-Saad M, Haron AW, et al.
    Microb Pathog, 2016 Feb;91:141-54.
    PMID: 26706347 DOI: 10.1016/j.micpath.2015.12.003
    Haemorrhagic septicaemia is a disease caused by Pasteurella multocida serotype B: 2 and E: 2. The organism causes acute, highly fatal septicaemic disease with high morbidity and mortality in cattle and more susceptible in buffaloes. Lipopolysaccharide can be found on the outer cell wall of the organism. Lipopolysaccharide is released during multiplication which leads to inflammatory reaction. It represents the endotoxin of P. multocida type B: 2 and responsible for toxicity in haemorrhagic septicaemia which plays an important role in the pathogenesis of the disease. Therefore, the aim of this study was to investigate the clinical signs, blood parameters, gross post mortem lesions and histopathology changes caused by P. multocida type B:2 immunogen lipopolysaccharide infections initiated through intravenous and oral routes of infection. 9 buffalo heifers were divided equally into 3 treatment groups. Group 1 was inoculated orally with 10 ml of phosphate buffer saline (PBS); Group 2 and 3 were inoculated with 10 ml of lipopolysaccharide broth intravenously and orally respectively. For the clinical signs, there were significant differences (p < 0.05) in temperature between the control, intravenous and oral group. In hematology and biochemistry findings, there were significant differences (p < 0.05) in erythrocytes, haemoglobin, PCV, MCV, lymphocytes, monocytes, eosinophils, GGT and albumin between the control, intravenous and oral group. However, there were no significant differences (p > 0.05) in the MCHC, leukocytes, band neutrophils, basophils, thrombocytes, plasma protein, icterus index, total protein, globulin and A:G ratio between intravenous and oral group. For Group 2 buffaloes, there were gross lesions in the lung, trachea, heart, liver, spleen, and kidney. In contrast, lesions were only observed in the lung, trachea and liver of Group 3 buffaloes. There were significant differences (p < 0.05) in hemorrhage and congestion; necrosis and degeneration; and inflammatory cells infiltration between experimental groups and control group. However, there were no significant differences (p > 0.05) in edema lesion between groups. In conclusion, this study is a proof that oral route infection of P. multocida type B:2 immunogen lipopolysaccharide can be used to stimulate host cell responses where oral vaccine through feed could be developed in the near future.
    MeSH terms: Animals; Buffaloes/blood; Buffaloes/immunology; Buffaloes/microbiology*; Cattle; Hematology; Lipopolysaccharides/immunology*; Pasteurella Infections/blood; Pasteurella Infections/microbiology; Pasteurella Infections/pathology; Pasteurella Infections/veterinary*; Virulence; Pasteurella multocida/immunology*; Pasteurella multocida/pathogenicity; Pasteurella multocida/physiology
  20. Bakhsheshi-Rad HR, Hamzah E, Kasiri-Asgarani M, Jabbarzare S, Iqbal N, Abdul Kadir MR
    Mater Sci Eng C Mater Biol Appl, 2016 Mar;60:526-537.
    PMID: 26706560 DOI: 10.1016/j.msec.2015.11.057
    The present study addressed the synthesis of a bi-layered nanostructured fluorine-doped hydroxyapatite (nFHA)/polycaprolactone (PCL) coating on Mg-2Zn-3Ce alloy via a combination of electrodeposition (ED) and dip-coating methods. The nFHA/PCL composite coating is composed of a thick (70-80 μm) and porous layer of PCL that uniformly covered the thin nFHA film (8-10 μm) with nanoneedle-like microstructure and crystallite size of around 70-90 nm. Electrochemical measurements showed that the nFHA/PCL composite coating presented a high corrosion resistance (R(p)=2.9×10(3) kΩ cm(2)) and provided sufficient protection for a Mg substrate against galvanic corrosion. The mechanical integrity of the nFHA/PCL composite coatings immersed in SBF for 10 days showed higher compressive strength (34% higher) compared with the uncoated samples, indicating that composite coatings can delay the loss of compressive strength of the Mg alloy. The nFHA/PCL coating indicted better bonding strength (6.9 MPa) compared to PCL coating (2.2 MPa). Immersion tests showed that nFHA/PCL composite-coated alloy experienced much milder corrosion attack and more nucleation sites for apatite compared with the PCL coated and uncoated samples. The bi-layered nFHA/PCL coating can be a good alternative method for the control of corrosion degradation of biodegradable Mg alloy for implant applications.
    MeSH terms: Alloys/chemistry*; Corrosion; Magnesium/chemistry*; Polyesters/chemistry*; Durapatite/chemistry*; Nanostructures/chemistry*
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