Browse publications by year: 2017

  1. Sahimin N, Lim YAL, Douadi B, Mohd Khalid MKN, Wilson JJ, Behnke JM, et al.
    Acta Trop, 2017 Sep;173:109-115.
    PMID: 28610937 DOI: 10.1016/j.actatropica.2017.06.011
    Ongoing urbanisation of the working population as well as cross-border migration of workers particularly into large cities has contributed to the development and growth of urban slums. These deprived areas are conducive for the transmission of intestinal pathogens including hookworm. The aim of this study was to determine both the prevalence and species identity of hookworm infections among the migrant worker community in Malaysia. A total of 388 faecal samples were collected from migrant workers between September 2014 and August 2015, representing workers from five employment sectors: construction, manufacturing, agriculture and plantations, food services and domestic services. Faecal samples were examined by microscopy and positive samples were subjected to molecular analysis. A total of 51 samples (13.1%) were positive by microscopy for hookworm infections. A two-step PCR based method amplifying a fragment of the 28S rRNA-ITS2 region was used to identify infections by Necator americanus and Ancylostoma spp. PCR products positive for Ancylostoma spp. were sequenced bidirectionally, and sequences analysed through BLAST and phylogenetic analysis. Samples containing Ancylostoma duodenale were further characterized by amplification and sequencing a fragment of cytochrome c oxidase subunit 1 (cox1) gene. PCR amplicons were successfully obtained from 42 (82.4%) of 51 samples, with 81.0% (34 of 42) identified as Necator americanus, 16.7% (7 of 42) as Ancylostoma spp. and 2.4% (1 of 42) as mixed infections of both species. All eight Ancylostoma spp. were confirmed to be Ancylostoma duodenale and this is the first time A. duodenale was reported in Malaysia. Samples containing A. duodenale from Nepalese and Indonesian workers shared high-similarity and were distinct compared to sequences from other countries. This study highlights the prevalence of hookworm infections among migrant workers living in Malaysia. Our findings underscore the necessity of screening migrant workers for hookworm infections, particularly those working in food-related services and industries.
    MeSH terms: Ancylostoma/genetics*; Animals; Base Sequence; Feces; Hookworm Infections/diagnosis*; Hookworm Infections/epidemiology; Hookworm Infections/parasitology*; Humans; Indonesia/epidemiology; Malaysia; Phylogeny; RNA, Ribosomal; Transients and Migrants*; Prevalence; Polymerase Chain Reaction; Necator americanus/genetics*
  2. Abdullah H, Abdul Wahab N, Abu Bakar K
    BMJ Case Rep, 2017 Jun 13;2017.
    PMID: 28611167 DOI: 10.1136/bcr-2017-219793
    MeSH terms: Adolescent; Female; Humans; Magnetic Resonance Imaging/methods*; Pregnancy; Prenatal Diagnosis/methods*; Twins, Conjoined*; Pregnancy, Twin*
  3. Azman AS, Othman I, Fang CM, Chan KG, Goh BH, Lee LH
    Indian J Microbiol, 2017 Jun;57(2):177-187.
    PMID: 28611495 DOI: 10.1007/s12088-016-0627-z
    Mangrove is a complex ecosystem that contains diverse microbial communities, including rare actinobacteria with great potential to produce bioactive compounds. To date, bioactive compounds extracted from mangrove rare actinobacteria have demonstrated diverse biological activities. The discovery of three novel rare actinobacteria by polyphasic approach, namely Microbacterium mangrovi MUSC 115T, Sinomonas humi MUSC 117T and Monashia flava MUSC 78T from mangrove soils at Tanjung Lumpur, Peninsular Malaysia have led to the screening on antibacterial, anticancer and neuroprotective activities. A total of ten different panels of bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, ATCC 70069, Pseudomonas aeruginosa NRBC 112582 and others were selected for antibacterial screening. Three different neuroprotective models (hypoxia, oxidative stress, dementia) were done using SHSY5Y neuronal cells while two human cancer cells lines, namely human colon cancer cell lines (HT-29) and human cervical carcinoma cell lines (Ca Ski) were utilized for anticancer activity. The result revealed that all extracts exhibited bacteriostatic effects on the bacteria tested. On the other hand, the neuroprotective studies demonstrated M. mangrovi MUSC 115T extract exhibited significant neuroprotective properties in oxidative stress and dementia model while the extract of strain M. flava MUSC 78T was able to protect the SHSY5Y neuronal cells in hypoxia model. Furthermore, the extracts of M. mangrovi MUSC 115T and M. flava MUSC 78T exhibited anticancer effect against Ca Ski cell line. The chemical analysis of the extracts through GC-MS revealed that the majority of the compounds present in all extracts are heterocyclic organic compound that could explain for the observed bioactivities. Therefore, the results obtained in this study suggested that rare actinobacteria discovered from mangrove environment could be potential sources of antibacterial, anticancer and neuroprotective agents.
  4. Lee SWH, Ooi L, Lai YK
    Front Pharmacol, 2017;8:330.
    PMID: 28611672 DOI: 10.3389/fphar.2017.00330
    Importance: Telemedicine has been shown to be an efficient and effective means of providing care to patients with chronic disease especially in remote and undeserved regions, by improving access to care and reduce healthcare cost. However, the evidence surrounding its applicability in type 1 diabetes remains scarce and conflicting. Objective: To synthesize evidence and quantify the effectiveness of telemedicine interventions for the management of glycemic and clinical outcomes in type 1 diabetes patients, relative to comparator conditions. Data Sources: MEDLINE, EMBASE, Cochrane Library, Web of Science, PsycINFO, and CINAHL were searched for published articles since inception until December 2016. Study Selection: Original articles reporting the results of randomized controlled studies on the effectiveness of telemedicine in people with type 1 diabetes were included. Data Extraction and Synthesis: Two reviewers independently extracted data, assessed quality, and strength of evidence. Interventions were categorized based upon the telemedicine focus (monitoring, education, consultation, case-management, and peer mentoring). Main Outcome and Measure: Absolute change in glycosylated hemoglobin A1c (HbA1c) from baseline to follow-up assessment. Results: A total of 38 studies described in 41 articles were identified. Positive effects on glycemic control were noted with studies examining telemedicine, with a mean reduction of 0.18% at the end of intervention. Studies with longer duration (>6 months) who had recruited patients with a higher baseline HbA1c (≥9%) were associated with larger effects. Telemedicine interventions that involve individualized assessments, audit with feedback and skill building were also more effective in improving glycemic control. However, no benefits were observed on blood pressure, lipids, weight, quality of life, and adverse events. Conclusions and Relevance: There is insufficient evidence to support telemedicine use for glycemic control and other clinically relevant outcome among patients with type 1 diabetes.
    MeSH terms: Diabetes Mellitus, Type 1; Humans; Telemedicine*
  5. Johdi NA, Ait-Tahar K, Sagap I, Jamal R
    Front Immunol, 2017;8:620.
    PMID: 28611777 DOI: 10.3389/fimmu.2017.00620
    Regulatory T cells (Tregs), a subset of CD4(+) or CD8(+) T cells, play a pivotal role in regulating immune homeostasis. An increase in Tregs was reported in many tumors to be associated with immune suppression and evasion in cancer patients. Despite the importance of Tregs, the molecular signatures that contributed to their pathophysiological relevance remain poorly understood and controversial. In this study, we explored the gene expression profiles in Tregs derived from patients with colorectal cancer [colorectal carcinoma (CRC), n = 15], colorectal polyps (P, n = 15), and in healthy volunteers (N, n = 15). Tregs were analyzed using CD4(+)CD25(+)CD127(low)FoxP3(+) antibody markers. Gene expression profiling analysis leads to the identification of 61 and 66 immune-related genes in Tregs derived from CRC and P patients, respectively, but not in N-derived Treg samples. Of these, 30 genes were differentially expressed both in CRC- and P-derived Tregs when compared to N-derived Tregs. Most of the identified genes were involved in cytokine/chemokine mediators of inflammation, chemokine receptor, lymphocyte activation, and T cell receptor (TCR) signaling pathways. This study highlights some of the molecular signatures that may affect Tregs' expansion and possible suppression of function in cancer development. Our findings may provide a better understanding of the immunomodulatory nature of Tregs and could, therefore, open up new avenues in immunotherapy.
    MeSH terms: Colonic Polyps; Homeostasis; Humans; Immunotherapy; Lymphocyte Activation; Receptors, Antigen, T-Cell; Colorectal Neoplasms; Cytokines; CD8-Positive T-Lymphocytes; Inflammation Mediators; Chemokines; Receptors, Chemokine; Gene Expression Profiling; T-Lymphocytes, Regulatory; Transcriptome; Healthy Volunteers
  6. Hadibarata T, Khudhair AB, Kristanti RA, Kamyab H
    Bioprocess Biosyst Eng, 2017 Sep;40(9):1411-1418.
    PMID: 28612166 DOI: 10.1007/s00449-017-1798-7
    Polycyclic aromatic hydrocarbon is a toxic recalcitrant environmental pollutant and its removal from the environment is very essential. In this study, a novel S1 strain isolated from the tropical rain forest was identified as Candida species based on 18S rRNA. The pyrene biodegradation was performed by Candida sp. S1. Pyrene was 35% degraded in 15 days. The percentage of pyrene biodegradation increased up to 75% with 24 g L-1of sodium chloride and decreased along with increasing salinity. Under the acidic condition, the biodegradation was increased up to 60% at pH 5. It was also found that the increasing glucose concentration of more than 10 g L-1had no significant effect on pyrene biodegradation, while agitation proved to have greater influence. There was a positive relationship between biomass growth and biodegradation rate of pyrene. One pyrene metabolite was identified from the extract solution and analyzed by a thin-layer chromatography, UV-visible absorption and gas chromatography-mass spectrometry. The metabolite found in the pyrene degradation was benzoic acid. Suitable conditions must be found to promote a successful microbial augmentation in liquid culture.
  7. Adnan N, Nordin SM, Rahman I, Amini MH
    Environ Sci Pollut Res Int, 2017 Aug;24(22):17955-17975.
    PMID: 28612311 DOI: 10.1007/s11356-017-9153-8
    With the rising concern about climate change, there has been an increased public awareness that has resulted in new government policies to support scientific research for mitigating these problems. Malaysia is among the major energy-intense countries and is under an excessive burden to advance its energy efficiency and to also work towards the reduction of its carbon emission. Plug-in hybrid electric vehicles (PHEVs) have the potential to lessen the carbon emission and gasoline consumption in order to alleviate environmental problems. Most of the energy problems linked to the increasing transportation pollution are now being reduced with the solution of the adoption of PHEVs. PHEVs are seen as a solution to cut carbon emission, which prevents environmental damages. Furthermore, PHEVs' driving range and performance can be comparable to the other hybrid vehicles as well as the conventional IC engines that have gasoline and diesel tanks. Thus, many efforts are being initiated to promote the use of PHEVs as an innovative and affordable transportation system. In order to achieve making the consumers aware of the adoption of PHEVs, we used a model which is based on the extended theory of planned behavior (TPB). This review is based on the factors affecting the adoption of PHEVs among Malaysian consumers. The model takes into account the ten key features that influence the adoption of PHEVs, such as environmental concern, personal norm, attitude, vehicle ownership costs, driving range, charging time, intention, subjective norm, perceived behavioral control, and personal norm. All these constructs are drivers towards the adoption of PHEVs. These factors affect the relationship between the adoption of PHEVs and how consumers intend to protect the environment. This review is based on improving how the "attitude-action" gap is understood as it is an important element for further studies on PHEVs. The aim of the research is to come up with a framework that examines how to modify the consumer's environmental concerns in acquiring PHEVs. This will pave the way for more academic research and future works that can emphasize how to obtain empirical results. The authors' recommendation is that, before a consumer's behavior is assessed and considered, an observation of the current technology is needed with methods and knowledge of the existing technology adoption aspect.
    MeSH terms: Vehicle Emissions/analysis*; Automobiles/classification*; Consumer Behavior/statistics & numerical data*; Malaysia; Models, Theoretical
  8. Mojiri A, Ahmad Z, Tajuddin RM, Arshad MF, Gholami A
    Environ Monit Assess, 2017 Jul;189(7):337.
    PMID: 28612336 DOI: 10.1007/s10661-017-6052-x
    Water pollution is a global problem. During current study, ammonia, phosphate, phenol, and copper(II) were removed from aqueous solution by subsurface and surface flow constructed wetland. In current investigation, distilled water was polluted with four contaminants including ammonia, phosphate, copper (Cu), and phenol. Response surface methodology and central composite design were applied to optimize pollutant removal during treatment by subsurface flow constructed wetland (SSFCW). Contact time (12 to 80 h) and initial pollutant concentration (20 to 85 mg/L) were selected as independent factors; some upper and lower ranges were also monitored for accuracy. In SSFCW, water hyacinth transplanted in two substrate layers, namely zeolite and cockle shell. SSFCW removed 87.7, 81.4, 74.7, and 54.9% of ammonia, phosphate, Cu, and phenol, respectively, at optimum contact time (64.5 h) and initial pollutant concentration (69.2 mg/L). Aqueous solution was moved to a surface flow constructed wetland (SFCW) after treating via SSFCW at optimum conditions. In SFCW, Typha was transplanted to a fixed powdered substrate layer, including bentonite, zeolite, and cockle shell. SFCW could develop performance of this combined system and could improve elimination efficacy of the four contaminants to 99.99%. So this combined CW showed a good performance in removing pollutants. Graphical abstract Wetlands arrangement for treating aqueous solution in current study.
    MeSH terms: Ammonia/analysis; Copper/analysis; Environmental Monitoring; Phenols; Phosphates/analysis; Water Pollutants, Chemical/analysis*; Water Pollution; Zeolites; Water Purification/methods; Phenol/analysis; Environmental Restoration and Remediation/methods*; Wetlands*
  9. Ayob FW, Simarani K, Zainal Abidin N, Mohamad J
    Microb Biotechnol, 2017 Jul;10(4):926-932.
    PMID: 28612376 DOI: 10.1111/1751-7915.12603
    This paper reports on the vinca alkaloid produced by a novel Nigrospora sphaerica isolated from Catharanthus roseus. Through liquid chromatography-mass spectrometry (LCMS), only the crude mycelia extract of this fungus was positive for determination of vinblastine. This vinca alkaloid was then purified by using high-performance liquid chromatography (HPLC) and tested for cytotoxicity activity using MTT assays. The breast cell line cancer (MDA-MB 231) was treated with a purified vinblastine which was intracellulary produced by N. sphaerica. The purified vinblastine from extracted leaf of C. roseus was used as a standard comparison. A positive result with a value of half maximal inhibitory concentration (IC50 ) of > 32 μg ml-1 was observed compared with standard (IC50 ) of 350 μg ml-1 only. It showed that a vinblastine produced by N. sphaerica has a high cytotoxicity activity even though the concentration of vinblastine produced by this endophytic fungus was only 0.868 μg ml-1 .
    MeSH terms: Antineoplastic Agents/isolation & purification; Antineoplastic Agents/metabolism*; Antineoplastic Agents/chemistry; Ascomycota/isolation & purification*; Ascomycota/metabolism*; Cell Survival/drug effects; Chromatography, Liquid; Formazans/analysis; Humans; Mass Spectrometry; Staining and Labeling; Tetrazolium Salts/analysis; Vinblastine/isolation & purification; Vinblastine/metabolism*; Vinblastine/chemistry; Inhibitory Concentration 50; Catharanthus/microbiology*; Cell Line, Tumor
  10. Mohd Zin F, Hillaluddin AH, Mustaffa J
    Asian Pac J Cancer Prev, 2017 05 01;18(5):1435-1443.
    PMID: 28612599
    Objective: This study aims to develop, validate and determine the reliability of an interactive multimedia strategy
    to prevent tobacco use among the young (TUPY-S) from an adolescents’ perspective. Methods: A descriptive study
    design was utilized. A modular instruction guideline by Russel (1974) was followed in the entire process, comprising
    a feasibility study, a review of existing modules, specification of the objectives, identification of the construct criterion
    items, learner analysis and entry behavior specification, establishment of the sequence instruction and media selection,
    a tryout with students and a field test. Result: Feasibility was agreed among the researchers and the school authorities.
    Culturally suitable rigorously developed tobacco use preventive strategies delivered using information technology (IT)
    are lacking in the literature. The objective of TUPY-S is to prevent tobacco use among adolescents living in Malaysia.
    Identified construct criterion items include knowledge, attitude, intention to use, self-efficacy, and refusal skill. The target
    population was early adolescents belonging to generation-Z. Content was developed from the adolescents’ perspective
    and delivered using IT in Malay language. Content validity, assessed by six experts in the field and module development,
    was good at 86%. The students’ tryout showed satisfactory face validity subjectively and objectively (85.5%) and
    high alpha Cronbach reliability (0.91). Conclusion: TUPY-S was confirmed to suit early adolescents of the current
    generation living in Malaysia. It demonstrated good content validity among the experts, satisfactory face validity and
    reliability among the target population. TUPY-S is ready to be evaluated for its effectiveness among early adolescents.
    MeSH terms: Adolescent; Attitude; Family Characteristics; Feasibility Studies; Humans; Information Science; Language; Malaysia; Schools; Students; Tobacco; Reproducibility of Results; Multimedia; Self Efficacy; Intention; Tobacco Use
  11. Monum T, Prasitwattanseree S, Das S, Siriphimolwat P, Mahakkanukrauh P
    Clin Ter, 2017 6 15;168(3):e203-e207.
    PMID: 28612898 DOI: 10.7417/T.2017.2007
    Sex estimation is an important step of postmortem investigation and the femur is a useful bone for sex estimation by using metric analysis method. Even though there have been a reported sex estimation method by using femur in Thais, the temporal change related to time and anthropological data need to be renewed. Thus the aim of this study is to re-evaluate sex estimation by femur in Thais. 97 adult male and 103 female femora were random chosen from Forensic osteology research center and 6 measurements were applied tend to. To compare with previous Thai data, mid shaft diameter to increase but femoral head and epicondylar breadth to stabilize and when tested previous discriminant function by vertical head diameter and epicondalar breadth, the accuracy of prediction was lower than previous report. From the new data, epicondalar breadth is the best variable for distinguishing male and female at 88.7 percent of accuracy, following by transverse and vertical head diameter at 86.7 percent and femoral neck diameter at 81.7 percent of accuracy. Multivariate discriminant analysis indicated transverse head diameter and epicondylar breadth performed highest rate of accuracy at 89.7 percent. The percent of accuracy of femur was close to previous reported sex estimation by talus and calcaneus in Thai population. Thus, for especially in case of lower limb remain, which absence of pelvis.
    MeSH terms: Adult; Aged; Aged, 80 and over; Female; Femur*; Humans; Male; Middle Aged; Thailand; Forensic Anthropology/methods*; Sex Determination by Skeleton*; Young Adult
  12. Daban KDY, Goh DYT
    Behav Sleep Med, 2017 07 17;17(3):281-290.
    PMID: 28613954 DOI: 10.1080/15402002.2017.1342168
    BACKGROUND AND OBJECTIVES: Optimal sleeping habits are important for health development of infants. The role of culture in sleep habits cannot be underestimated. We aimed to characterize sleep patterns, sleep practices, and sleep problems; and assess the sleep settings and parental perceptions of sleep problems in children from birth to 36 months in countries in the Southeast Asian (SEA) region.

    PARTICIPANTS: Parents and caregivers of infants and toddlers (birth to 36 months old) from countries in Southeast Asia participated in this study.

    METHODS: Data was collected using the Brief Infant Sleep Questionnaire for a total of 5,987 children from 6 countries in the SEA region (967 Indonesia/ID, 997 Malaysia/MY, 1,034 Philippines/PH, 1,001 Singapore/SG, 988 Thailand/TH, and 1,000 Vietnam/VN).

    RESULTS: The sleep variables varied among SEA children studied. Bedtimes and nighttime sleep varied across the region by as much as 1 hr 34 min and 1 hr 15 min respectively.

    CONCLUSIONS: Despite being geographically very close together and having some common sociocultural characteristics, sleep variables in the young child within the SEA region do differ in significant ways.
    MeSH terms: Asia, Southeastern; Child, Preschool; Habits; Humans; Indonesia; Infant; Malaysia; Parents; Philippines; Surveys and Questionnaires; Singapore; Sleep; Thailand; Vietnam; Caregivers
  13. Ho SC, Jacob SA, Tangiisuran B
    PLoS One, 2017;12(6):e0179290.
    PMID: 28614368 DOI: 10.1371/journal.pone.0179290
    BACKGROUND: One of the major challenges in treating major depressive disorder (MDD) is patients' non-adherence to medication. This study aimed to explore the barriers and facilitators of patients' adherence to antidepressants among outpatients with MDD.

    METHODS: Semi-structured and individual in-depth interviews were conducted among patients with MDD who were taking antidepressants, in the psychiatric clinic of a government-run hospital in Malaysia. Participants were purposively sampled from different genders and ethnicities. Interviews were conducted using a validated topic guide, and responses were audio-recorded, transcribed verbatim, checked, and analyzed using the grounded theory approach.

    RESULTS: A total of 30 patients were interviewed. Forty different themes and sub-themes were identified which were conceptually divided into two distinct categories related to barriers and facilitators to adherence. The barriers were: patient-specific, medication-specific, healthcare provision and system, social-cultural, and logistics. The facilitators were: having insight, perceived health benefits, regular activities, patient-provider relationship, reminders, and social support networks.

    CONCLUSIONS: Patient-specific barriers and medication side effects were the major challenges for adhering to treatment. Perceived health benefits and having insight on the need for treatment were the most frequently cited facilitators. Targeted interventions should be developed to address the key barriers, and promote measures to facilitate adherence in this group of patients.

    MeSH terms: Adult; Antidepressive Agents/adverse effects; Antidepressive Agents/therapeutic use*; Depressive Disorder, Major/drug therapy*; Depressive Disorder, Major/ethnology; Female; Humans; Male; Middle Aged; Surveys and Questionnaires; Risk Factors; Medication Adherence/ethnology; Medication Adherence/psychology*
  14. Matinnia N, Haghighi M, Jahangard L, Ibrahim FB, Rahman HA, Ghaleiha A, et al.
    Braz J Psychiatry, 2017 06 12;40(1):83-88.
    PMID: 28614494 DOI: 10.1590/1516-4446-2017-2229
    OBJECTIVE: Requests for elective cesarean delivery (ECD) have increased in Iran. While some sociodemographic and fear-related factors have been linked with this choice, psychological factors such as self-esteem, stress, and health beliefs are under-researched.

    METHODS: A total of 342 primigravidae (mean age = 25 years) completed questionnaires covering psychological dimensions such as self-esteem, perceived stress, marital relationship quality, perceived social support, and relevant health-related beliefs.

    RESULTS: Of the sample, 214 (62.6%) chose to undergo ECD rather than vaginal delivery (VD). This choice was associated with lower self-esteem, greater perceived stress, belief in higher susceptibility to problematic birth and barriers to an easy birth, along with lower perceived severity of ECD, fewer perceived benefits from VD, lower self-efficacy and a lower feeling of preparedness. No differences were found for marital relationship quality or perceived social support.

    CONCLUSIONS: The pattern suggests that various psychological factors such as self-esteem, self-efficacy, and perceived stress underpin the decision by primigravidae to have an ECD.

    MeSH terms: Adolescent; Adult; Cesarean Section/psychology*; Cross-Sectional Studies; Fear/psychology*; Female; Humans; Iran; Parity; Pregnancy; Surveys and Questionnaires; Self Concept; Socioeconomic Factors; Stress, Psychological; Gravidity; Parturition; Young Adult
  15. Yusof SR, Abbott NJ, Avdeef A
    Eur J Pharm Sci, 2017 Aug 30;106:274-286.
    PMID: 28614733 DOI: 10.1016/j.ejps.2017.06.016
    Most studies of blood-brain barrier (BBB) permeability and transport are conducted at a single pH, but more detailed information can be revealed by using multiple pH values. A pH-dependent biophysical model was applied to the mechanistic analysis of published pH-dependent BBB luminal uptake data from three opioid derivatives in rat: pentazocine (Suzuki et al., 2002a, 2002b), naloxone (Suzuki et al., 2010a), and oxycodone (Okura et al., 2008). Two types of data were processed: in situ brain perfusion (ISBP) and brain uptake index (BUI). The published perfusion data were converted to apparent luminal permeability values, Papp, and analyzed by the pCEL-X program (Yusof et al., 2014), using the pH-dependent Crone-Renkin equation (pH-CRE) to determine the impact of cerebrovascular flow on the Michaelis-Menten transport parameters (Avdeef and Sun, 2011). For oxycodone, the ISBP data had been measured at pH7.4 and 8.4. The present analysis indicates a 7-fold lower value of the cerebrovascular flow velocity, Fpf, than that expected in the original study. From the pyrilamine-inhibited data, the flow-corrected passive intrinsic permeability value was determined to be P0=398×10-6cm·s-1. The uptake data indicate that the neutral form of oxycodone is affected by a transporter at pH8.4. The extent of the cation uptake was less certain from the available data. For pentazocine, the brain uptake by the BUI method had been measured at pH5.5, 6.5, and 7.4, in a concentration range 0.1-40mM. Under similar conditions, ISBP data were also available. The pH-CRE determined values of Fpf from both methods were nearly the same, and were smaller than the expected value in the original publication. The transport of the cationic pentazocine was not fully saturated at pH5.5 at 40mM. The transport of the neutral species at pH7.4 appeared to reach saturation at 40mM pentazocine concentration, but not at 12mM. In the case of naloxone, a pH-dependent Michaelis-Menten equation (pH-MME) analysis of the data indicated a smooth sigmoidal transition from a higher capacity uptake process affecting cationic naloxone (pH5.0-7.0) to a lower capacity uptake process affecting the neutral drug (pH8.0-8.5), with cross-over point near pH7.4. Evidently, measurements at multiple pH values can reveal important information about both cerebrovascular flow and BBB transport kinetics.
    MeSH terms: Analgesics, Opioid/pharmacokinetics*; Animals; Biological Transport; Blood-Brain Barrier/metabolism*; Hydrogen-Ion Concentration; Kinetics; Models, Biological; Naloxone/pharmacokinetics*; Oxycodone/pharmacokinetics*; Pentazocine/pharmacokinetics*; Permeability; Rats
  16. Amekyeh H, Billa N, Roberts C
    Int J Pharm, 2017 Jan 30;517(1-2):42-49.
    PMID: 27923696 DOI: 10.1016/j.ijpharm.2016.12.001
    Oral delivery of pharmaceuticals requires that they retain their physical and chemical attributes during transit within the gastrointestinal (GI) tract, for the manifestation of desired therapeutic profiles. Solid lipid nanoparticles (SLNs) are used as carriers to improve the absorption of hydrophobic drugs. In this study, we examine the stability of amphotericin B (AmB) and paracetamol (PAR) SLNs in simulated GI fluids during gastric emptying. On contact with the simulated fluids, the particles increased in size due to ingress of the dissolution media into the particles. Simulated gastric emptying revealed that the formulations had mean sizes <350nm and neutral surface charges, both of which are optimal for intestinal absorption of SLNs. There was ingress of the fluids into the SLNs, followed by diffusion of the dissolved drug, whose rate depended on the solubility of the loaded-drug in the particular medium. Time-of-flight secondary ion mass spectrometry analyses indicated that drug loading followed the core-shell model and that the AmB SLNs have a more drug-enriched core than the PAR SLNs do. The AmB SLNs are therefore a very suitable carrier of AmB for oral delivery. The stability of the SLNs in the simulated GI media indicates their suitability for oral delivery.
    MeSH terms: Acetaminophen/administration & dosage; Acetaminophen/pharmacology*; Acetaminophen/chemistry; Administration, Oral; Amphotericin B/administration & dosage; Amphotericin B/pharmacology*; Amphotericin B/chemistry; Drug Carriers/chemistry*; Drug Stability; Gastric Emptying/drug effects*; Humans; Lipids/chemistry*; Models, Biological; Surface Properties; Nanoparticles/chemistry*
  17. Dalu T, Wasserman RJ, Tonkin JD, Alexander ME, Dalu MTB, Motitsoe SN, et al.
    Sci Total Environ, 2017 Dec 01;601-602:1340-1348.
    PMID: 28605853 DOI: 10.1016/j.scitotenv.2017.06.023
    Understanding the drivers of community structure is fundamental for adequately managing ecosystems under global change. Here we used a large dataset of eighty-four headwater stream sites in three catchments in the Eastern Highlands of Zimbabwe, which represent a variety of abiotic conditions and levels of impairment, to examine the drivers of benthic macroinvertebrate community structure. We focused our assessment on macroinvertebrate family level community composition and functional feeding group classifications. Taxonomic richness was weakly positively correlated with ammonium, phosphates and pH, and weakly negatively correlated with detrital cover and dissolved oxygen. Measured abiotic variables, however, had limited influence on both macroinvertebrate diversity and functional feeding group structure, with the exception of ammonium, channel width and phosphates. This reflected the fact that many macroinvertebrate families and functional feeding guilds were well represented across a broad range of habitats. Predatory macroinvertebrates were relatively abundant, with collector-filterers having the lowest relative abundances. The findings of the study suggest that for certain ecological questions, a more detailed taxonomic resolution may be required to adequately understand the ecology of aquatic macroinvertebrates within river systems. We further recommend management and conservation initiatives on the Save River system, which showed significant impact from catchment developmental pressures, such as urbanisation, agriculture and illegal mining.
    MeSH terms: Agriculture; Animals; Environmental Monitoring; Invertebrates*; Mining; Urbanization; Zimbabwe; Multivariate Analysis; Ecosystem*; Biodiversity*; Rivers/chemistry*
  18. Yong YK, Tan HY, Saeidi A, Rosmawati M, Atiya N, Ansari AW, et al.
    Innate Immun, 2017 07;23(5):459-467.
    PMID: 28606013 DOI: 10.1177/1753425917714854
    Hepatitis B virus (HBV) infection is a major cause of chronic liver disease that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses represent the key determinants of HBV clearance or persistence. Here, we investigated the role of the early activation marker, CD69 and effector cytokines, granzyme B (GrB) and IFN-γ in the exhaustion of innate-like TCR Vα7.2+CD4+T cells, in 15 individuals with chronic HBV (CHB) infection where six were HBV DNA+ and nine were HBV DNA-. The percentage of cytokine-producing T cells and MAIT cells were significantly perturbed in HBV patients relative to healthy controls (HCs). The intracellular expression of GrB and IFN-γ was significantly reduced in MAIT cells derived from HBV-infected patients as compared to HCs, and the levels correlated with the percentage and levels [mean fluorescence intensity (MFI)] of CD69 expression. The total expression of CD69 (iMFI) was lower in CHB patients as compared to HCs. The frequency of CD69+ cells correlated with the levels of cytokine expression (MFI), particularly in CHB patients as compared to HCs. In summary, the polyfunctionality of peripheral T cells was significantly reduced among CHB patients, especially in the TCR Vα7.2+CD4+T cells, and the levels of cytokine expression correlated with functional cytokine levels.
    MeSH terms: Adult; Antigens, Differentiation, T-Lymphocyte/metabolism*; Cells, Cultured; Cytotoxicity, Immunologic; Female; Hepatitis B virus/physiology*; Carcinoma, Hepatocellular/immunology*; Humans; Immunity, Innate; Interferon-gamma/metabolism; Liver Neoplasms/immunology*; Lymphocyte Activation; Male; Middle Aged; CD4-Positive T-Lymphocytes/immunology*; Antigens, CD/metabolism*; Receptors, Antigen, T-Cell, alpha-beta/metabolism; Viral Load; Hepatitis B, Chronic/immunology*; Lectins, C-Type/metabolism*; Granzymes/metabolism; Mucosal-Associated Invariant T Cells/immunology*
  19. Lee PY, Chin SF, Neoh HM, Jamal R
    J Biomed Sci, 2017 Jun 12;24(1):36.
    PMID: 28606141 DOI: 10.1186/s12929-017-0342-z
    The human gut is home to complex microbial populations that change dynamically in response to various internal and external stimuli. The gut microbiota provides numerous functional benefits that are crucial for human health but in the setting of a disturbed equilibrium, the microbial community can cause deleterious outcomes such as diseases and cancers. Characterization of the functional activities of human gut microbiota is fundamental to understand their roles in human health and disease. Metaproteomics, which refers to the study of the entire protein collection of the microbial community in a given sample is an emerging area of research that provides informative details concerning functional aspects of the microbiota. In this mini review, we present a summary of the progress of metaproteomic analysis for studying the functional role of gut microbiota. This is followed by an overview of the experimental approaches focusing on fecal specimen for metaproteomics and is concluded by a discussion on the challenges and future directions of metaproteomic research.
    MeSH terms: Gastrointestinal Microbiome*; Humans; Proteome*; Proteomics*
  20. Yap HY, Muria-Gonzalez MJ, Kong BH, Stubbs KA, Tan CS, Ng ST, et al.
    Microb Cell Fact, 2017 Jun 12;16(1):103.
    PMID: 28606152 DOI: 10.1186/s12934-017-0713-x
    BACKGROUND: Genome mining facilitated by heterologous systems is an emerging approach to access the chemical diversity encoded in basidiomycete genomes. In this study, three sesquiterpene synthase genes, GME3634, GME3638, and GME9210, which were highly expressed in the sclerotium of the medicinal mushroom Lignosus rhinocerotis, were cloned and heterologously expressed in a yeast system.

    RESULTS: Metabolite profile analysis of the yeast culture extracts by GC-MS showed the production of several sesquiterpene alcohols (C15H26O), including cadinols and germacrene D-4-ol as major products. Other detected sesquiterpenes include selina-6-en-4-ol, β-elemene, β-cubebene, and cedrene. Two purified major compounds namely (+)-torreyol and α-cadinol synthesised by GME3638 and GME3634 respectively, are stereoisomers and their chemical structures were confirmed by 1H and 13C NMR. Phylogenetic analysis revealed that GME3638 and GME3634 are a pair of orthologues, and are grouped together with terpene synthases that synthesise cadinenes and related sesquiterpenes. (+)-Torreyol and α-cadinol were tested against a panel of human cancer cell lines and the latter was found to exhibit selective potent cytotoxicity in breast adenocarcinoma cells (MCF7) with IC50 value of 3.5 ± 0.58 μg/ml while α-cadinol is less active (IC50 = 18.0 ± 3.27 μg/ml).

    CONCLUSIONS: This demonstrates that yeast-based genome mining, guided by transcriptomics, is a promising approach for uncovering bioactive compounds from medicinal mushrooms.

    MeSH terms: Agaricales/genetics; Agaricales/chemistry*; Antineoplastic Agents/metabolism*; Antineoplastic Agents/pharmacology; Antineoplastic Agents/chemistry; Cell Survival/drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism*; Sesquiterpenes/metabolism*; Sesquiterpenes/pharmacology; Sesquiterpenes/chemistry; Structure-Activity Relationship; Molecular Structure; Alkyl and Aryl Transferases/genetics; Alkyl and Aryl Transferases/metabolism; Cell Line, Tumor
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