Browse publications by year: 2017

  1. Tan BK, Tan SB, Chen LC, Chang KM, Chua SS, Balashanker S, et al.
    Patient Prefer Adherence, 2017;11:1027-1034.
    PMID: 28652712 DOI: 10.2147/PPA.S132894
    PURPOSE: Poor adherence to tyrosine kinase inhibitors (TKIs) could compromise the control of chronic myeloid leukemia (CML) and contributes to poorer survival. Little is known about how medication-related issues affect CML patients' adherence to TKI therapy in Malaysia. This qualitative study aimed to explore these issues.

    PATIENTS AND METHODS: Individual face-to-face, semistructured interviews were conducted at the hematology outpatient clinics of two medical centers in Malaysia from August 2015 to January 2016. CML patients aged ≥18 years who were prescribed a TKI were invited to participate in the study. Interviews were audio-recorded, transcribed verbatim, and thematically analyzed.

    RESULTS: Four themes were identified from 18 interviews: 1) concerns about adverse reactions to TKIs, 2) personal beliefs regarding the use of TKIs, 3) mismanagement of TKIs in daily lives, and 4) financial burden in accessing treatment. Participants skipped their TKIs due to ineffective emesis control measures and perceived wastage of medication from vomiting. Participants also modified their TKI therapy due to fear of potential harm from long-term use, and stopped taking their TKIs based on belief in curative claims of traditional medicines and misconception about therapeutic effects of TKIs. Difficulty in integrating the dosing requirements of TKIs into daily lives led to unintentional skipping of doses, as well as the risk of toxicities from inappropriate dosing intervals or food interactions. Furthermore, financial constraints also resulted in delayed initiation of TKIs, missed clinic appointments, and treatment interruptions.

    CONCLUSION: Malaysian CML patients encountered a range of medication-related issues leading to a complex pattern of nonadherence to TKI therapy. Further studies should investigate whether regular contact with patients to improve understanding of treatment rationale, to elicit and address patients' concerns about adverse reactions, and to empower patients with skills to self-manage their medications might promote better adherence to TKIs and improve CML patients' outcome.

    Study site: hematology outpatient clinics of Ampang Hospital (AH) and University Malaya Medical Centre (UMMC) in Malaysia
    MeSH terms: Adult; Hospitals, University; Humans; Malaysia; Outpatient Clinics, Hospital; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Qualitative Research; Medication Adherence*
  2. Balakrishnan N, Teo SH, Sinnadurai S, Bhoo Pathy NT, See MH, Taib NA, et al.
    World J Surg, 2017 11;41(11):2735-2745.
    PMID: 28653143 DOI: 10.1007/s00268-017-4081-9
    BACKGROUND: Reproductive factors are associated with risk of breast cancer, but the association with breast cancer survival is less well known. Previous studies have reported conflicting results on the association between time since last childbirth and breast cancer survival. We determined the association between time since last childbirth (LCB) and survival of women with premenopausal and postmenopausal breast cancers in Malaysia.

    METHOD: A historical cohort of 986 premenopausal, and 1123 postmenopausal, parous breast cancer patients diagnosed from 2001 to 2012 in University Malaya Medical Centre were included in the analyses. Time since LCB was categorized into quintiles. Multivariable Cox regression was used to determine whether time since LCB was associated with survival following breast cancer, adjusting for demographic, tumor, and treatment characteristics.

    RESULTS: Premenopausal breast cancer patients with the most recent childbirth (LCB quintile 1) were younger, more likely to present with unfavorable prognostic profiles and had the lowest 5-year overall survival (OS) (66.9; 95% CI 60.2-73.6%), compared to women with longer duration since LCB (quintile 2 thru 5). In univariable analysis, time since LCB was inversely associated with risk of mortality and the hazard ratio for LCB quintile 2, 3, 4, and 5 versus quintile 1 were 0.53 (95% CI 0.36-0.77), 0.49 (95% CI 0.33-0.75), 0.61 (95% CI 0.43-0.85), and 0.64 (95% CI 0.44-0.93), respectively; P trend = 0.016. However, this association was attenuated substantially following adjustment for age at diagnosis and other prognostic factors. Similarly, postmenopausal breast cancer patients with the most recent childbirth were also more likely to present with unfavorable disease profiles. Compared to postmenopausal breast cancer patients in LCB quintile 1, patients in quintile 5 had a higher risk of mortality. This association was not significant following multivariable adjustment.

    CONCLUSION: Time since LCB is not independently associated with survival in premenopausal or postmenopausal breast cancers. The apparent increase in risks of mortality in premenopausal breast cancer patients with a recent childbirth, and postmenopausal patients with longer duration since LCB, appear to be largely explained by their age at diagnosis.

    MeSH terms: Adult; Age Factors; Aged; Breast Neoplasms/mortality*; Female; Humans; Malaysia/epidemiology; Middle Aged; Prognosis; Risk Factors; Time Factors; Survival Rate; Proportional Hazards Models; Reproductive History; Premenopause*; Postmenopause*; Parturition*
  3. Joanne S, Vythilingam I, Teoh BT, Leong CS, Tan KK, Wong ML, et al.
    Trop Med Int Health, 2017 09;22(9):1154-1165.
    PMID: 28653334 DOI: 10.1111/tmi.12918
    OBJECTIVE: To determine the susceptibility status of Aedes albopictus with and without Wolbachia to the four dengue virus serotypes.

    METHODS: Two newly colonised colonies of Ae. albopictus from the wild were used for the study. One colony was naturally infected with Wolbachia while in the other Wolbachia was removed by tetracycline treatment. Both colonies were orally infected with dengue virus-infected fresh blood meal. Dengue virus load was measured using quantitative RT-PCR at four-time intervals in the salivary glands, midguts and ovaries.

    RESULTS: Wolbachia did not significantly affect Malaysian Ae. albopictus dengue infection or the dissemination rate for all four dengue virus serotypes. Malaysian Ae. albopictus had the highest replication kinetics for DENV-1 and the highest salivary gland and midgut infection rate for DENV-4.

    CONCLUSION: Wolbachia, which naturally exists in Malaysian Ae. albopictus, does not significantly affect dengue virus replication. Malaysian Ae. albopictus is susceptible to dengue virus infections and capable of transmitting dengue virus, especially DENV-1 and DENV-4. Removal of Wolbachia from Malaysian Ae. albopictus would not reduce their susceptibility status.

    MeSH terms: Animals; Bacterial Infections/complications; Dengue/transmission*; Dengue/virology; Dengue Virus/classification; Dengue Virus/pathogenicity*; Humans; Insect Vectors*; Virus Replication*; Polymerase Chain Reaction; Wolbachia*; Serogroup*
  4. Teow SY, Ali SA
    Pak J Pharm Sci, 2017 May;30(3):891-895.
    PMID: 28653935
    This study evaluated the impact of pH (7.4 and 6.5), bovine serum albumin (BSA), and human serum albumin (HSA) on Curcumin activity against 2 reference, 1 clinical, and 10 environmental strains of Staphylococcus aureus (S. aureus). Minimal inhibitory concentrations (MICs) of Curcumin against S. aureus were statistically indifferent (p>0.05) at pH7.4 and pH6.5. Activity of Curcumin against S. aureus was reduced by two folds in the presence of 1.25-5% BSA/HSA.
    MeSH terms: Animals; Anti-Bacterial Agents/pharmacology; Cattle; Curcumin/pharmacology*; Humans; Hydrogen-Ion Concentration; Microbial Sensitivity Tests; Serum Albumin/chemistry; Staphylococcus aureus/drug effects; In Vitro Techniques
  5. Cai H, Xu LL, Lai HY, Liu JY, Ng SW, Li D
    Chem Commun (Camb), 2017 Jun 27.
    PMID: 28654101 DOI: 10.1039/c7cc03350h
    A new adenine-containing metal-organic framework (MOF), [Zn4O(adenine)4(benzene-1,3-dicarboxylate)4Zn2] (named as ZnBDCA), was synthesized solvothermally. ZnBDCA possesses high quantum yield (>50%) and nano-channels that can encapsulate acriflavine molecules to build a host-guest chemopalette for approaching white-light emission.
    MeSH terms: Acriflavine; Adenine; Benzene; Carboxylic Acids; Light; Names
  6. Ariffin H, Azanan MS, Abd Ghafar SS, Oh L, Lau KH, Thirunavakarasu T, et al.
    Cancer, 2017 Nov 01;123(21):4207-4214.
    PMID: 28654149 DOI: 10.1002/cncr.30857
    BACKGROUND: Large epidemiologic studies have reported the premature onset of age-related conditions, such as ischemic heart disease and diabetes mellitus, in childhood cancer survivors, decades earlier than in their peers. The authors investigated whether young adult survivors of childhood acute lymphoblastic leukemia (ALL) have a biologic phenotype of cellular ageing and chronic inflammation.

    METHODS: Plasma inflammatory cytokines were measured using a cytometric bead array in 87 asymptomatic young adult survivors of childhood ALL (median age, 25 years; age range, 18-35 years) who attended annual follow-up clinic and compared with healthy, age-matched and sex-matched controls. Leukocyte telomere length (LTL) was measured using Southern blot analysis.

    RESULTS: Survivors had significant elevation of plasma interleukin-2 (IL-2), IL-10, IL-17a, and high-sensitivity C-reactive protein levels (all P 0.8 mg/dL) was related to increased odds of having metabolic syndrome (odds ratio, 7.256; 95% confidence interval, 1.501-35.074). Survivors also had significantly shorter LTL compared with controls (median, 9866 vs 10,392 base pairs; P = .021). Compared with published data, LTL in survivors was similar to that in healthy individuals aged 20 years older. Survivors who received cranial irradiation had shorter LTL compared with those who had not (P = .013).

    CONCLUSIONS: Asymptomatic young adult survivors of childhood ALL demonstrate a biologic profile of chronic inflammation and telomere attrition, consistent with an early onset of cellular processes that drive accelerated aging. These processes may explain the premature development of age-related chronic conditions in childhood cancer survivors. Understanding their molecular basis may facilitate targeted interventions to disrupt the accelerated aging process and its long-term impact on overall health. Cancer 2017;123:4207-4214. © 2017 American Cancer Society.

    MeSH terms: Adult Survivors of Child Adverse Events*; Adolescent; Adult; Aging; C-Reactive Protein/analysis*; Chronic Disease; Female; Humans; Inflammation/blood*; Interleukin-2/blood; Interleukins/blood*; Male; Phenotype*; Biomarkers/blood; Case-Control Studies; Cranial Irradiation/adverse effects; Telomere/radiation effects; Interleukin-10/blood; Cell Aging*; Interleukin-17/blood; Young Adult; Telomere Shortening*
  7. Thomas J, Idris NA, Collings DA
    J Microsc, 2017 10;268(1):13-27.
    PMID: 28654160 DOI: 10.1111/jmi.12582
    Pontamine fast scarlet 4B is a red paper and textiles dye that has recently been introduced as a fluorescent probe for plant cell walls. Pontamine exhibits bifluorescence, or fluorescence dependent on the polarization of the excitation light: Because cellulose is aligned within the cell wall, pontamine-labelled cell walls exhibit variable fluorescence as the excitation polarization is modulated. Thus, bifluorescence measurements require polarized excitation that can be directly or indirectly modulated. In our confocal microscopy observations of various cellulose samples labelled with pontamine, we modulated excitation polarization either through sample rotation or by the confocal's scanfield rotation function. This variably rotated laser polarizations on Leica confocal microscopes, but not those from other makers. Beginning with samples with directly observable microfibril orientations, such as purified bacterial cellulose, the velamen of orchid roots and the inner S2 layer of radiata pine compression wood, we demonstrate that modelling the variations in pontamine fluorescence with a sine curve can be used to measure the known microfibril angles. We then measured average local microfibril angles in radiata pine samples, and showed similar microfibril angles in compression and normal (opposite) wood. Significantly, bifluorescence measurements might also be used to understand the degree of local cellulose alignment within the cell wall, as opposed to variations in the overall cellulose angle.
    MeSH terms: Cell Wall; Cellulose; Fluorescence; Fluorescent Dyes; Paper; Rotation; Textiles; Wood; Microscopy, Confocal; Microfibrils; Pinus; Plant Cells
  8. Nam HY, Balaji Raghavendran HR, Pingguan-Murphy B, Abbas AA, Merican AM, Kamarul T
    PLoS One, 2017;12(6):e0178117.
    PMID: 28654695 DOI: 10.1371/journal.pone.0178117
    The role for mechanical stimulation in the control of cell fate has been previously proposed, suggesting that there may be a role of mechanical conditioning in directing mesenchymal stromal cells (MSCs) towards specific lineage for tissue engineering applications. Although previous studies have reported that calcium signalling is involved in regulating many cellular processes in many cell types, its role in managing cellular responses to tensile loading (mechanotransduction) of MSCs has not been fully elucidated. In order to establish this, we disrupted calcium signalling by blocking stretch-activated calcium channel (SACC) in human MSCs (hMSCs) in vitro. Passaged-2 hMSCs were exposed to cyclic tensile loading (1 Hz + 8% for 6, 24, 48, and 72 hours) in the presence of the SACC blocker, gadolinium. Analyses include image observations of immunochemistry and immunofluorescence staining from extracellular matrix (ECM) production, and measuring related tenogenic and apoptosis gene marker expression. Uniaxial tensile loading increased the expression of tenogenic markers and ECM production. However, exposure to strain in the presence of 20 μM gadolinium reduced the induction of almost all tenogenic markers and ECM staining, suggesting that SACC acts as a mechanosensor in strain-induced hMSC tenogenic differentiation process. Although cell death was observed in prolonged stretching, it did not appear to be apoptosis mediated. In conclusion, the knowledge gained in this study by elucidating the role of calcium in MSC mechanotransduction processes, and that in prolonged stretching results in non-apoptosis mediated cell death may be potential useful for regenerative medicine applications.
    MeSH terms: Aged; Calcium Channel Agonists/pharmacology*; Cell Differentiation/drug effects*; Cells, Cultured; Collagen/metabolism; Extracellular Matrix/metabolism; Fibronectins/metabolism; Gadolinium/pharmacology*; Humans; Middle Aged; Stress, Mechanical*; Cadherins/metabolism; Apoptosis/drug effects; Tissue Engineering; Mechanotransduction, Cellular/drug effects; Mesenchymal Stromal Cells/cytology; Mesenchymal Stromal Cells/drug effects*; Mesenchymal Stromal Cells/metabolism
  9. Ong HH, Tan YN, Say YH
    Physiol Behav, 2017 01 01;168:128-137.
    PMID: 27847178 DOI: 10.1016/j.physbeh.2016.11.006
    We determined whether single nucleotide polymorphisms (SNPs; rs1761667 and rs1527483) in the fatty acid translocase CD36 gene - a receptor for fatty acids - is associated with oral fat perception (OFP) of different fat contents in custards and commercially-available foods, and obesity measures in Malaysian subjects (n=313; 118 males, 293 ethnic Chinese; 20 ethnic Indians). A 170-mm visual analogue scale was used to assess the ratings of perceived fat content, oiliness and creaminess of 0%, 2%, 6% and 10% fat content-by-weight custards and low-fat/regular versions of commercially-available milk, mayonnaise and cream crackers. Overall, the subjects managed to significantly discriminate the fat content, oiliness and creaminess between low-fat/regular versions of milk and mayonnaise. Females rated the perception of fat content and oiliness of both milks higher, but ethnicity, obesity and adiposity status did not seem to play a role in influencing most of OFP. The overall minor allele frequencies for rs1761667 and rs1527483 were 0.30 and 0.26, respectively. Females and individuals with rs1527483 TT genotype significantly perceived greater creaminess of 10% fat-by-weight custard. Also, individuals with rs1527483 TT genotype and T allele significantly perceived greater fat content of cream crackers, independent of fat concentration. rs1761667 SNP did not significantly affect OFP, except for cream crackers. Both gene variants were also not associated with obesity measures. Taken together, this study supports the notion that CD36 - specifically rs1527483, plays a role in OFP, but not in influencing obesity in Malaysian subjects. Besides, gender is an important factor for OFP, where females had higher sensitivity.
    MeSH terms: Adolescent; Fats*; Female; Humans; Malaysia; Male; Mouth/innervation; Antigens, CD36/genetics*; Polymorphism, Single Nucleotide/genetics*; Asian Continental Ancestry Group/genetics; Taste Perception/genetics*; Young Adult
  10. Lim D, Parumo R, Chai MB, Shanmuganathan J
    J Oral Implantol, 2017 Jun;43(3):228-231.
    PMID: 27996585 DOI: 10.1563/aaid-joi-D-16-00172
    Displacement of dental implants into the maxillary sinus is a rare complication. This article presents a case of displaced dental implant into maxillary sinus. Retrieval of the dental implant from left maxillary sinus was performed via endoscopic sinus surgery. This case highlighted a delayed referral of a 53-year-old male by a general dental practitioner for management of a dislodged dental implant into the left maxillary antrum. The implant was dislodged during placement of a healing abutment 4 months after implant insertion to replace missing 25. Cone beam computerized tomography revealed the displaced implant was located at the ostium of the left nose. A sudden change in sinonasal pressure when the patient took a deep breath during the procedure may have created a negative pressure and suction effect causing the implant to be dislodged and embedded at the ostium. In view of its position, a referral to an otorhinolaryngologist was made for endoscopic removal of the displaced implant. This case also highlighted the need for inter disciplinary cooperation in the management of such a complication for the best interest of the patients.
    MeSH terms: Endoscopy/methods*; Foreign-Body Migration/surgery*; Humans; Male; Maxillary Sinus/surgery*; Middle Aged; Nose/surgery; Dental Implants*; Cone-Beam Computed Tomography
  11. Oei JL, Saugstad OD, Lui K, Wright IM, Smyth JP, Craven P, et al.
    Pediatrics, 2017 01;139(1).
    PMID: 28034908 DOI: 10.1542/peds.2016-1452
    BACKGROUND AND OBJECTIVES: Lower concentrations of oxygen (O2) (≤30%) are recommended for preterm resuscitation to avoid oxidative injury and cerebral ischemia. Effects on long-term outcomes are uncertain. We aimed to determine the effects of using room air (RA) or 100% O2 on the combined risk of death and disability at 2 years in infants <32 weeks' gestation.

    METHODS: A randomized, unmasked study designed to determine major disability and death at 2 years in infants <32 weeks' gestation after delivery room resuscitation was initiated with either RA or 100% O2 and which were adjusted to target pulse oximetry of 65% to 95% at 5 minutes and 85% to 95% until NICU admission.

    RESULTS: Of 6291 eligible patients, 292 were recruited and 287 (mean gestation: 28.9 weeks) were included in the analysis (RA: n = 144; 100% O2: n = 143). Recruitment ceased in June 2014, per the recommendations of the Data and Safety Monitoring Committee owing to loss of equipoise for the use of 100% O2. In non-prespecified analyses, infants <28 weeks who received RA resuscitation had higher hospital mortality (RA: 10 of 46 [22%]; than those given 100% O2: 3 of 54 [6%]; risk ratio: 3.9 [95% confidence interval: 1.1-13.4]; P = .01). Respiratory failure was the most common cause of death (n = 13).

    CONCLUSIONS: Using RA to initiate resuscitation was associated with an increased risk of death in infants <28 weeks' gestation. This study was not a prespecified analysis, and it was underpowered to address this post hoc hypothesis reliably. Additional data are needed.

    MeSH terms: Air; Child, Preschool; Female; Follow-Up Studies; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature*; Intensive Care Units, Neonatal; Male; Oximetry/methods; Oxygen Inhalation Therapy/adverse effects; Oxygen Inhalation Therapy/methods*; Resuscitation/methods*; Resuscitation/mortality; Risk; Hospital Mortality; Disabled Children
  12. Ngorsuraches S, Chaiyakunapruk N, Jianfei Guo J, Yang BM
    Value Health Reg Issues, 2017 05;12:99-100.
    PMID: 28648323 DOI: 10.1016/j.vhri.2017.04.002
    MeSH terms: Asia; Cost-Benefit Analysis*; Delivery of Health Care; Developing Countries; Humans; Policy Making*; Technology Assessment, Biomedical/economics; Technology Assessment, Biomedical/trends*
  13. Uni S, Fukuda M, Ogawa K, Lim YA, Agatsuma T, Bunchom N, et al.
    Parasitol Int, 2017 Oct;66(5):593-595.
    PMID: 28648713 DOI: 10.1016/j.parint.2017.06.006
    An 11-year-old boy living in Otsu City, Shiga Prefecture, Kansai Region, Western Honshu, Japan had zoonotic onchocercosis. The patient developed a painful swelling on the little finger of his left hand. The worm detected in the excised mass had external transverse ridges but did not have inner striae in the cuticle. On the basis of the parasite's histopathological characteristics, the causative agent was identified as a female Onchocerca dewittei japonica (Spirurida: Onchocercidae). The species of the filarial parasite was confirmed by sequencing the cox1 gene of the parasite. The Japanese wild boar Sus scrofa leucomystax is a definitive host for O. dewittei japonica, which is then transmitted by blackflies as the vector to humans. The current case described occurred in the Kansai Region, Western Honshu, where such infections were previously not reported.
    MeSH terms: Animals; Child; Female; Humans; Insect Vectors/parasitology; Japan; Male; Onchocerca/genetics; Onchocerca/isolation & purification*; Onchocerciasis/diagnosis*; Onchocerciasis/parasitology*; Onchocerciasis/veterinary; Simuliidae/parasitology; Swine; Swine Diseases/parasitology; Zoonoses; Genes, Helminth; Sus scrofa/parasitology
  14. Amin AKMR, Tanaka M, Al-Saari N, Feng G, Mino S, Ogura Y, et al.
    Syst Appl Microbiol, 2017 Jul;40(5):290-296.
    PMID: 28648725 DOI: 10.1016/j.syapm.2017.04.003
    Two phylogenetically distinct Vibrionaceae strains C4II189Tand C4V358Tisolated from reef seawater off Ishigaki Island, Japan, in 2014 were studied with advanced genome-based taxonomy approaches. All aspects of phylogenetic (16S rRNA phylogeny, MLSA), phenotypic and genetic (ANI, DDH, AAI, and the number of core genes) cohesions between the two identified species were high enough to propose them as members of a new genus within the family Vibrionaceae. Consequently, an eighth genus Thaumasiovibrio gen. nov. is proposed that contains two new species Thaumasiovibrio occultus sp. nov. strain C4II189T(=DSM 101554T=JCM 31629T) (type species) and Thaumasiovibrio subtropicus sp. nov. strain C4V358T(=DSM 101555T=JCM 31630T). Thaumasiovibrio species were phylogenetically distinct from the other Vibrionaceae species based on pyrH gene sequences. The combination of catalase negative, sensitivity to vibriostatic agent O/129, and green colony formation on TCBS for the phylogenetically affiliated strains was the diagnostic features for the current tentative identification of this genus.
    MeSH terms: Animals; Base Composition/genetics; DNA, Bacterial/genetics; Japan; Phylogeny; RNA, Ribosomal, 16S/genetics; Seawater/microbiology*; Sequence Analysis, DNA; Anthozoa/microbiology*; Coral Reefs*; Multilocus Sequence Typing
  15. Bigliardi PL, Alsagoff SAL, El-Kafrawi HY, Pyon JK, Wa CTC, Villa MA
    Int J Surg, 2017 Aug;44:260-268.
    PMID: 28648795 DOI: 10.1016/j.ijsu.2017.06.073
    BACKGROUND: Of the many antimicrobial agents available, iodophore-based formulations such as povidone iodine have remained popular after decades of use for antisepsis and wound healing applications due to their favorable efficacy and tolerability. Povidone iodine's broad spectrum of activity, ability to penetrate biofilms, lack of associated resistance, anti-inflammatory properties, low cytotoxicity and good tolerability have been cited as important factors, and no negative effect on wound healing has been observed in clinical practice. Over the past few decades, numerous reports on the use of povidone iodine have been published, however, many of these studies are of differing design, endpoints, and quality. More recent data clearly supports its use in wound healing.

    METHODS: Based on data collected through PubMed using specified search criteria based on above topics and clinical experience of the authors, this article will review preclinical and clinical safety and efficacy data on the use of povidone iodine in wound healing and its implications for the control of infection and inflammation, together with the authors' advice for the successful treatment of acute and chronic wounds.

    RESULTS AND CONCLUSION: Povidone iodine has many characteristics that position it extraordinarily well for wound healing, including its broad antimicrobial spectrum, lack of resistance, efficacy against biofilms, good tolerability and its effect on excessive inflammation. Due to its rapid, potent, broad-spectrum antimicrobial properties, and favorable risk/benefit profile, povidone iodine is expected to remain a highly effective treatment for acute and chronic wounds in the foreseeable future.

    MeSH terms: Anti-Infective Agents, Local/therapeutic use*; Humans; Povidone-Iodine/therapeutic use*; Surgical Wound Infection/prevention & control*; Wound Healing/drug effects*
  16. Nishimura A, Sunggip C, Oda S, Numaga-Tomita T, Tsuda M, Nishida M
    Pharmacol Ther, 2017 Dec;180:113-128.
    PMID: 28648830 DOI: 10.1016/j.pharmthera.2017.06.010
    Purinergic signaling, mediated mainly by G protein-coupled P2Y receptors (P2YRs), is now attracting attention as a new therapeutic target for preventing or treating cardiovascular diseases. Observations using mice with genetically modified P2YRs and/or treated with a pharmacological P2YR inhibitor have helped us understand the physiological and pathological significance of P2YRs in the cardiovascular system. P2YR-mediated biological functions are predominantly activated by mononucleotides released from non-adrenergic, non-cholinergic nerve endings or non-secretory tissues in response to physical stress or cell injury, though recent studies have suggested the occurrence of ligand-independent P2YR function through receptor-receptor interactions (oligomerization) in several biological processes. In this review, we introduce the functions of P2YRs and possible dimerization with G protein-coupled receptors (GPCRs) in the cardiovascular system. We focus especially on the crosstalk between uridine nucleotide-responsive P2Y6R and angiotensin (Ang) II type1 receptor (AT1R) signaling, and introduce our recent finding that the P2Y6R antagonist MRS2578 interrupts heterodimerization between P2Y6R and AT1R, thereby reducing the risk of AT1R-stimulated hypertension in mice. These results strongly suggest that targeting P2Y6R oligomerization could be an effective new strategy to reduce the risk of cardiovascular diseases.
    MeSH terms: Animals; Cardiovascular Diseases/drug therapy*; Cardiovascular Diseases/metabolism; Homeostasis; Humans; Myocardium/metabolism; Risk Factors; Receptors, Purinergic P2Y/metabolism*; Receptors, Purinergic P2Y/chemistry
  17. Dent E, Lien C, Lim WS, Wong WC, Wong CH, Ng TP, et al.
    J Am Med Dir Assoc, 2017 Jul 01;18(7):564-575.
    PMID: 28648901 DOI: 10.1016/j.jamda.2017.04.018
    OBJECTIVE: To develop Clinical Practice Guidelines for the screening, assessment and management of the geriatric condition of frailty.

    METHODS: An adapted Grading of Recommendations, Assessment, Development, and Evaluation approach was used to develop the guidelines. This process involved detailed evaluation of the current scientific evidence paired with expert panel interpretation. Three categories of Clinical Practice Guidelines recommendations were developed: strong, conditional, and no recommendation.

    RECOMMENDATIONS: Strong recommendations were (1) use a validated measurement tool to identify frailty; (2) prescribe physical activity with a resistance training component; and (3) address polypharmacy by reducing or deprescribing any inappropriate/superfluous medications. Conditional recommendations were (1) screen for, and address modifiable causes of fatigue; (2) for persons exhibiting unintentional weight loss, screen for reversible causes and consider food fortification and protein/caloric supplementation; and (3) prescribe vitamin D for individuals deficient in vitamin D. No recommendation was given regarding the provision of a patient support and education plan.

    CONCLUSIONS: The recommendations provided herein are intended for use by healthcare providers in their management of older adults with frailty in the Asia Pacific region. It is proposed that regional guideline support committees be formed to help provide regular updates to these evidence-based guidelines.

    MeSH terms: Aged; Asia; Female; Humans; Male; Middle Aged; Patient Care Planning/standards*; Geriatric Assessment/statistics & numerical data*; Frail Elderly/statistics & numerical data*; Evidence-Based Medicine; Disease Management
  18. Imran S, Taha M, Selvaraj M, Ismail NH, Chigurupati S, Mohammad JI
    Bioorg Chem, 2017 08;73:121-127.
    PMID: 28648924 DOI: 10.1016/j.bioorg.2017.06.007
    A series of twenty indole hydrazone analogs (1-21) were synthesized, characterized by different spectroscopic techniques such as 1H NMR and EI-MS, and screened for α-amylase inhibitory activity. All analogs showed a variable degree of α-amylase inhibition with IC50 values ranging between 1.66 and 2.65μM. Nine compounds that are 1 (2.23±0.01μM), 8 (2.44±0.12μM), 10 (1.92±0.12μM), 12 (2.49±0.17μM), 13 (1.66±0.09μM), 17 (2.25±0.1μM), 18 (1.87±0.25μM), 20 (1.83±0.63μM), and 19 (1.97±0.02μM) showed potent α-amylase inhibition when compared with the standard acarbose (1.05±0.29μM). Other analogs showed good to moderate α-amylase inhibition. The structure activity relationship is mainly focusing on difference of substituents on phenyl part. Molecular docking studies were carried out to understand the binding interaction of the most active compounds.
    MeSH terms: alpha-Amylases/antagonists & inhibitors*; alpha-Amylases/metabolism; Dose-Response Relationship, Drug; Enzyme Inhibitors/chemical synthesis; Enzyme Inhibitors/pharmacology*; Enzyme Inhibitors/chemistry; Humans; Indoles/chemical synthesis; Indoles/pharmacology*; Indoles/chemistry; Structure-Activity Relationship; Molecular Structure; Molecular Docking Simulation
  19. Teow SY, Ali SA
    Pak J Pharm Sci, 2017 Mar;30(2):449-457.
    PMID: 28649069
    Antibacterial effect is one of the major therapeutic activities of plant-derived Curcumin. This work evaluated the effect of serum albumin, human plasma, and whole blood on the in vitro activity of Curcumin against eight clinical bacterial isolates by standard broth microdilution and plate-counting methods. Toxicological effects of Curcumin towards human red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) were also investigated. Curcumin exhibited weak activity against gram-negative bacteria, except Escherichia coli and Shigella flexneri were susceptible and was most active against gram-positive bacteria: Staphylococcus aureus, Streptococcus pyogenes and Enterococcus faecalis. The antibacterial activity was impaired in the presence of bovine serum albumin (BSA), human plasma and whole blood. Curcumin was not toxic to PBMCs and RBCs at 200μg/mL. Furthermore, Curcumin showed synergistic activity in combination with antibiotics: Ciprofloxacin, Gentamicin, Vancomycin and Amikacin against Staphylococcus aureus. This study demonstrated that the interaction of Curcumin with plasma proteins diminishes its in vitro antibacterial activity. Curcumin derivatives with reduced affinity for plasma protein may improve the bioavailability and antibacterial activities.
    MeSH terms: Anti-Bacterial Agents/adverse effects; Anti-Bacterial Agents/pharmacology*; Blood Physiological Phenomena*; Curcumin/adverse effects; Curcumin/pharmacology*; Drug Synergism; Erythrocytes/drug effects; Humans; Leukocytes, Mononuclear/drug effects; Microbial Sensitivity Tests; Serum Albumin/adverse effects*
  20. Jumat NR, Chong MY, Seman Z, Jamaluddin R, Wong NK, Abdullah M
    Front Immunol, 2017;8:680.
    PMID: 28649252 DOI: 10.3389/fimmu.2017.00680
    Sexual dimorphism in immune response is widely recognized, but few human studies have observed this distinction. Food with endo-immunomodulatory potential may reveal novel sex-biased in vivo interactions. Immunomodulatory effects of Carica papaya were compared between healthy male and female individuals. Volunteers were given fixed meals supplemented with papaya for 2 days. Changes in blood immune profiles and hormone levels were determined. In females, total natural killer (NK) cell percentages decreased (12.7 ± 4.4 vs 14.6 ± 5.8%, p = 0.018, n = 18) while B cells increased (15.2 ± 5.5 vs 14.5 ± 5.0, p = 0.037, n = 18) after papaya consumption. Increased 17β-estradiol (511.1 ± 579.7 vs 282.7 ± 165.0 pmol/l, p = 0.036, n = 9) observed in females may be crucial to this change. Differentiation markers (CD45RA, CD69, CD25) analyzed on lymphocytes showed naïve (CD45RA(+)) non-CD4(+) lymphocytes were reduced in females (40.7 ± 8.1 vs 46.8 ± 5.4%, p = 0.012, n = 8) but not males. A general suppressive effect of papaya on CD69(+) cells, and higher percentage of CD69(+) populations in females and non-CD4 lymphocytes, may be relevant. CD107a(+) NK cells were significantly increased in males (16.8 ± 7.0 vs 14.7 ± 4.8, p = 0.038, n = 9) but not females. Effect in females may be disrupted by the action of progesterone, which was significantly correlated with this population (R = 0.771, p = 0.025, n = 8) after papaya consumption. In males, total T helper cells were increased (33.4 ± 6.4 vs 32.4 ± 6.1%, p = 0.040, n = 15). Strong significant negative correlation between testosterone and CD25(+)CD4(+) lymphocytes, may play a role in the lower total CD4(+) T cells reported in males. Thus, dissimilar immune profiles were elicited in the sexes after papaya consumption and may have sex hormone influence.
    MeSH terms: Antigens, Differentiation; B-Lymphocytes; Estradiol; Female; T-Lymphocytes, Helper-Inducer; Humans; Killer Cells, Natural; Male; Progesterone; Sex Characteristics; Testosterone; Volunteers; Carica
External Links