Browse publications by year: 2017

  1. Lee V, Kwong D, Leung TW, Lam KO, Tong CC, Lee A
    Crit Rev Oncol Hematol, 2017 Jun;114:13-23.
    PMID: 28477740 DOI: 10.1016/j.critrevonc.2017.03.030
    Nasopharyngeal carcinoma (NPC) is endemic in Southern China, Taiwan, Malaysia, Singapore, North Africa and Alaska. About 30% of NPC patients develop recurrence or metastasis despite initial radical treatment. Palliative chemotherapy is the first-line treatment for inoperable recurrence or distant metastatic disease. However the standard first-line chemotherapeutic regimen is yet to be established until recently gemcitabine and cisplatin has been proven superior to traditional regimen with 5-FU and cisplatin shown in a phase III randomized-controlled trial. Further palliative systemic treatment options including other chemotherapeutic regimens, targeted therapy and more recently immunotherapy have gradually evolved. We provided a comprehensive review on different traditional chemotherapeutic regimens and highlighted the latest chemotherapeutic treatments as well as the latest development of targeted therapies, immune checkpoint inhibitors and other immunotherapeutic options in this setting.
  2. Ahmed M, Chin YH, Guo X, Zhao XM
    J Environ Sci (China), 2017 May;55:1-10.
    PMID: 28477801 DOI: 10.1016/j.jes.2016.06.014
    The study of trace metals in the atmosphere and lake water is important due to their critical effects on humans, aquatic animals and the geochemical balance of ecosystems. The objective of this study was to investigate the concentration of trace metals in atmospheric and lake water samples during the rainy season (before and after precipitation) between November and December 2015. Typical methods of sample preparation for trace metal determination such as cloud point extraction, solid phase extraction and dispersive liquid-liquid micro-extraction are time-consuming and difficult to perform; therefore, there is a crucial need for development of more effective sample preparation procedure. A convection microwave assisted digestion procedure for extraction of trace metals was developed for use prior to inductively couple plasma-mass spectrometric determination. The result showed that metals like zinc (133.50-419.30μg/m(3)) and aluminum (53.58-378.93μg/m(3)) had higher concentrations in atmospheric samples as compared to lake samples before precipitation. On the other hand, the concentrations of zinc, aluminum, chromium and arsenic were significantly higher in lake samples after precipitation and lower in atmospheric samples. The relationship between physicochemical parameters (pH and turbidity) and heavy metal concentrations was investigated as well. Furthermore, enrichment factor analysis indicated that anthropogenic sources such as soil dust, biomass burning and fuel combustion influenced the metal concentrations in the atmosphere.
  3. Kanakaraju D, Ravichandar S, Lim YC
    J Environ Sci (China), 2017 May;55:214-223.
    PMID: 28477816 DOI: 10.1016/j.jes.2016.05.043
    The use of nanosized titanium dioxide (TiO2) and zinc oxide (ZnO) in the suspension form during treatment makes the recovering and recycling of photocatalysts difficult. Hence, supported photocatalysts are preferred for practical water treatment applications. This study was conducted to investigate the efficiency of calcium alginate (CaAlg) beads that were immobilized with hybrid photocatalysts, TiO2/ZnO to form TiO2/ZnO-CaAlg. These immobilized beads, with three different mass ratios of TiO2:ZnO (1:1, 1:2, and 2:1) were used to remove Cu(II) in aqueous solutions in the presence of ultraviolet light. These beads were subjected to three cycles of photocatalytic treatment with different initial Cu(II) concentrations (10-80ppm). EDX spectra have confirmed the inclusion of Ti and Zn on the surface of the CaAlg beads. Meanwhile, the surface morphology of the beads as determined using SEM, has indicated differences of before and after the photocatalytic treatment of Cu(II). Among all three, the equivalent mass ratio TiO2/ZnO-CaAlg beads have shown the best performance in removing Cu(II) during all three recycling experiments. Those TiO2/ZnO-CaAlg beads have also shown consistent removal of Cu, ranging from 7.14-62.0ppm (first cycle) for initial concentrations of 10-80ppm. In comparison, bare CaAlg was only able to remove 6.9-48ppm of similar initial Cu concentrations. Thus, the potential use of TiO2/ZnO-CaAlg beads as environmentally friendly composite material can be further extended for heavy metal removal from contaminated water.
  4. Ameirika, Sha HX, Hwang JS
    Toxicon, 2017 Jul;133:153-161.
    PMID: 28478056 DOI: 10.1016/j.toxicon.2017.05.007
    Hydra actinoporin-like toxin-1 (HALT-1) is a 20.8 kDa pore-forming toxin isolated from Hydra magnipapillata. HALT-1 shares structural similarity with actinoporins, a family that is well known for its haemolytic and cytolytic activity. However, the precise pore-forming mechanism of HALT-1 remains an open question since little is known about the specific target binding for HALT-1. For this reason, a comprehensive proteomic analysis was performed using affinity purification and SILAC-based mass spectrometry to identify potential protein-protein interactions between mammalian HeLa cell surface proteins and HALT-1. A total of 4 mammalian proteins was identified, of which only folate receptor alpha was further verified by ELISA. Our preliminary results highlight an alternative-binding mode of HALT-1 to the human plasma membrane. This is the first evidence showing that HALT-1, an actinoporin-like protein, binds to a membrane protein, the folate receptor alpha. This study would advance our understanding of the molecular basis of toxicity of pore-forming toxins and provide new insights in the production of more potent inhibitors for the toxin-membrane receptor interactions.
    MeSH terms: Animals; Chromatography, Affinity; HeLa Cells; Humans; Hydra*; Marine Toxins/toxicity; Marine Toxins/chemistry*; Membrane Proteins/metabolism; Protein Binding; Mass Spectrometry; Proteomics; Pore Forming Cytotoxic Proteins/toxicity; Pore Forming Cytotoxic Proteins/chemistry*; Folate Receptor 1/metabolism
  5. Abba Y, Ilyasu YM, Noordin MM
    Microb Pathog, 2017 Jul;108:49-54.
    PMID: 28478198 DOI: 10.1016/j.micpath.2017.04.038
    AIM: Captivity of non-venomous snakes such as python and boa are common in zoos, aquariums and as pets in households. Poor captivity conditions expose these reptiles to numerous pathogens which may result in disease conditions. The purpose of this study was to investigate the common bacteria isolated from necropsied captive snakes in Malaysia over a five year period.

    MATERIALS AND METHODS: A total of 27 snake carcasses presented for necropsy at the Universiti Putra Malaysia (UPM) were used in this survey. Samples were aseptically obtained at necropsy from different organs/tissues (lung, liver, heart, kindey, oesophagus, lymph node, stomach, spinal cord, spleen, intestine) and cultured onto 5% blood and McConkey agar, respectively. Gram staining, morphological evaluation and biochemical test such as oxidase, catalase and coagulase were used to tentatively identify the presumptive bacterial isolates.

    RESULTS: Pythons had the highest number of cases (81.3%) followed by anaconda (14.8%) and boa (3.7%). Mixed infection accounted for 81.5% in all snakes and was highest in pythons (63%). However, single infection was only observed in pythons (18.5%). A total of 82.7%, 95.4% and 100% of the bacterial isolates from python, anaconda and boa, respectively were gram negative. Aeromonas spp was the most frequently isolated bacteria in pythons and anaconda with incidences of 25 (18%) and 8 (36.6%) with no difference (p > 0.05) in incidence, respectively, while Salmonella spp was the most frequently isolated in boa and significantly higher (p 

    MeSH terms: Aeromonas/isolation & purification; Aeromonas/pathogenicity; Animals; Animal Structures/microbiology; Animals, Zoo; Bacteria/classification*; Bacteria/isolation & purification*; Bacteria/pathogenicity; Malaysia; Public Health; Salmonella/isolation & purification; Salmonella/pathogenicity; Snakes/microbiology*; Zoonoses/microbiology*; Boidae/microbiology; Coinfection
  6. Khan G, Basirun WJ, Kazi SN, Ahmed P, Magaji L, Ahmed SM, et al.
    J Colloid Interface Sci, 2017 Sep 15;502:134-145.
    PMID: 28478220 DOI: 10.1016/j.jcis.2017.04.061
    The inhibitory effect of two Schiff bases 3-(5-methoxy-2-hydroxybenzylideneamino)-2-(-5-methoxy-2-hydroxyphenyl)-2,3-dihydroquinazoline-4(1H)-one (MMDQ), and 3-(5-nitro-2-hydroxybenzylideneamino)-2(5-nitro-2-hydroxyphenyl)-2,3-dihydroquinazoline-4(1H)-one (NNDQ) on the corrosion of mild steel in 1M hydrochloric acid were studied using mass loss, potentiodynamic polarization technique and electrochemical impedance spectroscopy measurements at ambient temperature. The investigation results indicate that the Schiff Bases compounds with an average efficiency of 92% at 1.0mM of additive concentration have fairly effective inhibiting properties for mild steel in hydrochloric acid, and acts as mixed type inhibitor character. The inhibition efficiencies measured by all measurements show that the inhibition efficiencies increase with increase in inhibitor concentration. This reveals that the inhibitive mechanism of inhibitors were primarily due to adsorption on mild steel surface, and follow Langmuir adsorption isotherm. The temperature effect on the inhibition process in 1MHCl with the addition of investigated Schiff bases was studied at a temperature range of 30-60°C, and the activation parameters (Ea, ΔH and ΔS) were calculated to elaborate the corrosion mechanism. The differences in efficiency for two investigated inhibitors are associated with their chemical structures.
  7. Deng D, Zhang P, Guo Y, Lim TO
    Ann Rheum Dis, 2017 Aug;76(8):1436-1439.
    PMID: 28478399 DOI: 10.1136/annrheumdis-2017-211073
    OBJECTIVE: We evaluate the efficacy of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) for the treatment of lupus nephritis (LN). Previous reports showed hUC-MSC could have dramatic treatment effect.

    METHODS: Eighteen patients with WHO class III or IV LN were randomly assigned to hUC-MSC (dose 2×108 cells) or placebo. All patients received standard immunosuppressive treatment, which consisted of intravenous methylprednisolone and cyclophosphamide, followed by maintenance oral prednisolone and mycophenolate mofetil.

    RESULTS: Remission occurred in 9 of 12 patients (75%) in the hUC-MSC group and 5 of 6 patients (83%) in the placebo group. Remission was defined as stabilisation or improvement in renal function, reduction in urinary red cells and protein. A similar proportion of patients on hUC-MSC and placebo achieved complete remission. Improvements in serum albumin, complement, renal function, Systemic Lupus Erythematosus Disease Activity Index and British Isles Lupus Assessment Group scores were similar in both groups. One patient on placebo had a stroke and another had ascites. One patient on hUC-MSC had leucopenia, pneumonia and subcutaneous abscess and another died of severe pneumonia. The trial was abandoned after 18 patients were enrolled when it had become obvious it would not demonstrate a positive treatment effect.

    CONCLUSION: hUC-MSC has no apparent additional effect over and above standard immunosuppression.

    TRIAL REGISTRATION NUMBER: NCT01539902; Results.

    MeSH terms: Adult; Cyclophosphamide/therapeutic use; Double-Blind Method; Drug Therapy, Combination; Female; Glucocorticoids/therapeutic use*; Humans; Immunosuppressive Agents/therapeutic use*; Lupus Nephritis/therapy*; Male; Methylprednisolone/therapeutic use; Mycophenolic Acid/therapeutic use; Remission Induction; Transplantation, Homologous; Umbilical Cord/cytology; Treatment Outcome; Mesenchymal Stem Cell Transplantation/methods*; Young Adult; Early Termination of Clinical Trials; Maintenance Chemotherapy; Induction Chemotherapy
  8. Ng KY, Leong MK, Liang H, Paxinos G
    Brain Struct Funct, 2017 Sep;222(7):2921-2939.
    PMID: 28478550 DOI: 10.1007/s00429-017-1439-6
    Melatonin, through its different receptors, has pleiotropic functions in mammalian brain. Melatonin is secreted mainly by the pineal gland and exerts its effects via receptor-mediated and non-receptor-mediated actions. With recent advancement in neuroanatomical mapping, we may now understand better the localizations of the two G protein-coupled melatonin receptors MT1 and MT2. The abundance of these melatonin receptors in respective brain regions suggests that receptor-mediated actions of melatonin might play crucial roles in the functions of central nervous system. Hence, this review aims to summarize the distribution of melatonin receptors in the brain and to discuss the putative functions of melatonin in the retina, cerebral cortex, reticular thalamic nucleus, habenula, hypothalamus, pituitary gland, periaqueductal gray, dorsal raphe nucleus, midbrain and cerebellum. Studies on melatonin receptors in the brain are important because cumulative evidence has pointed out that melatonin receptors not only play important physiological roles in sleep, anxiety, pain and circadian rhythm, but might also be involved in the pathogenesis of a number of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and Huntington's disease.
    MeSH terms: Alzheimer Disease; Animals; Anxiety; Cerebellum; Cerebral Cortex; Circadian Rhythm; Huntington Disease; Hypothalamus; Melatonin; Pain; Parkinson Disease; Periaqueductal Gray; Pineal Gland; Pituitary Gland; Retina; Habenula; Receptors, Melatonin; Dorsal Raphe Nucleus
  9. Beh ZY, Hasan MS
    J Vasc Access, 2017 Sep 11;18(5):e57-e61.
    PMID: 28478621 DOI: 10.5301/jva.5000720
    INTRODUCTION: We report the use of a newly described regional technique, ultrasound-guided costoclavicular approach infraclavicular brachial plexus block for surgical anesthesia in two high-risk patients undergoing 2nd stage transposition of basilic vein fistula.

    METHODS: Both patients had features of difficult airway, American Society of Anesthesiologists (ASA) physical status class III and central venous occlusive disease. The common approach, i.e., ultrasound-guided supraclavicular brachial plexus block was technically difficult with inherent risk of vascular puncture due to dilated venous collaterals at the supraclavicular area possibly compromising block quality. The risk of general anesthesia (GA) was significant as patients were morbidly obese with possible risk of obstructive sleep apnea postoperatively. As an alternative, we performed the ultrasound-guided costoclavicular approach infraclavicular brachial plexus block with 20 mL local anesthetic (LA) ropivacaine 0.5% delivered at the identified costoclavicular space using in-plane needling technique. Another 10 mL of LA was infiltrated along the subcutaneous fascia of the proximal medial aspect of arm.

    RESULTS: Both surgeries of >2 hours' duration were successful, without the need of further local infiltration at surgical site or conversion to GA.

    CONCLUSIONS: Ultrasound-guided costoclavicular approach can be an alternative way of providing effective analgesia and safe anesthesia for vascular access surgery of the upper limb.

    MeSH terms: Amides/administration & dosage*; Amides/adverse effects; Anesthetics, Local/administration & dosage*; Anesthetics, Local/adverse effects; Arteriovenous Shunt, Surgical/methods*; Brachial Artery/physiopathology; Brachial Artery/surgery*; Brachial Plexus/drug effects*; Humans; Kidney Failure, Chronic/complications; Kidney Failure, Chronic/diagnosis; Kidney Failure, Chronic/therapy*; Male; Obesity, Morbid/complications; Veins/physiopathology; Veins/surgery*; Treatment Outcome; Ultrasonography, Interventional*; Upper Extremity/blood supply*; Operative Time; Brachial Plexus Block/adverse effects; Brachial Plexus Block/methods*
  10. Bazazi AR, Wickersham JA, Wegman MP, Culbert GJ, Pillai V, Shrestha R, et al.
    Contemp Clin Trials, 2017 08;59:1-12.
    PMID: 28479216 DOI: 10.1016/j.cct.2017.05.006
    Incarcerated people living with HIV and opioid dependence face enormous challenges to accessing evidence-based treatment during incarceration and after release into the community, placing them at risk of poor HIV treatment outcomes, relapse to opioid use and accompanying HIV transmission risk behaviors. Here we describe in detail the design and implementation of Project Harapan, a prospective clinical trial conducted among people living with HIV and opioid dependence who transitioned from prison to the community in Malaysia from 2010 to 2014. This trial involved 2 interventions: within-prison initiation of methadone maintenance therapy and an evidence-based behavioral intervention adapted to the Malaysian context (the Holistic Health Recovery Program for Malaysia, HHRP-M). Individuals were recruited and received the interventions while incarcerated and were followed for 12months after release to assess post-release HIV transmission risk behaviors and a range of other health-related outcomes. Project Harapan was designed as a fully randomized 2×2 factorial trial where individuals would be allocated in equal proportions to methadone maintenance therapy and HHRP-M, methadone maintenance therapy alone, HHRP-M alone, or control. Partway through study implementation, allocation to methadone maintenance therapy was changed from randomization to participant choice; randomization to HHRP-M continued throughout. We describe the justification for this study; the development and implementation of these interventions; changes to the protocol; and screening, enrollment, treatment receipt, and retention of study participants. Logistical, ethical, and analytic issues associated with the implementation of this study are discussed.
    MeSH terms: Adult; Behavior Therapy/methods*; Female; Humans; Malaysia; Male; Methadone/pharmacology*; Narcotics/pharmacology; Prisoners/psychology*; Prisons; Research Design; Substance Abuse Treatment Centers/methods; Outcome Assessment (Health Care); Evidence-Based Practice; Opiate Substitution Treatment/methods*
  11. Raja SB, Rajendiran V, Kasinathan NK, P A, Venkatabalasubramanian S, Murali MR, et al.
    Food Chem Toxicol, 2017 Aug;106(Pt A):92-106.
    PMID: 28479391 DOI: 10.1016/j.fct.2017.05.006
    Quercetin is a bioactive compound with anti-inflammatory, antioxidant and anticancer properties. This study exemplifies the differential cytotoxic activity of Quercetin on two human colonic cancer cell lines, HT29 and HCT15. IC50 of Quercetin for HT29 and HCT15 cells were 42.5 μM and 77.4 μM, respectively. Activation of caspase-3, increased level of cytosolic cytochrome c, decreased levels of pAkt, pGSK-3β and cyclin D1 in 40 μM Quercetin treated HT29 cells alone. Though, nuclear translocation of NFkB was increased in 40 μM Quercetin treated HT29 and HCT15 cells, over expression of COX-2 was observed in 40 μM Quercetin treated HT29 cells, whereas, Quercetin treated HCT15 cells did not expressed COX-2. Increased generation of reactive oxygen species (ROS) was observed only in Quercetin treated HT29 cells, which is due to over expression of COX-2, as COX-2 silencing inhibited Quercetin induced apoptosis and ROS generation. Insilico analysis provided evidence that Quercetin could partially inhibit COX-2 enzyme by binding to subunit A which has peroxidase activity and serves as source of ROS. However, Quercetin showed minimal effect on normal intestinal epithelial cells i,e IEC-6. To conclude, differential sensitivity of two cancer cells, HT29 and HCT15, to Quercetin depends on COX-2 dependent ROS generation that induces apoptosis and inhibits cell survival.
    MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*; Colonic Neoplasms/enzymology*; Colonic Neoplasms/genetics; Colonic Neoplasms/metabolism; Colonic Neoplasms/physiopathology; Humans; Quercetin/pharmacology*; NF-kappa B/genetics; NF-kappa B/metabolism; Apoptosis/drug effects; Reactive Oxygen Species/metabolism*; Cell Line, Tumor; Cell Proliferation/drug effects; Cyclooxygenase 2/genetics; Cyclooxygenase 2/metabolism*
  12. Singhal K, Raj N, Gupta K, Singh S
    J Oral Maxillofac Pathol, 2017;21(1):107-114.
    PMID: 28479696 DOI: 10.4103/0973-029X.203758
    Tea is produced from the Camellia sinensis plant and can generally be divided into categories based on how they are processed. In general, green tea that is unfermented C. sinensis has been considered superior to black tea in health benefits. It contains a unique set of catechins that possess biological activity as antioxidant, anti-inflammatory and antiproliferative, which is potentially significant to the prevention and treatment of various forms of diseases. Oral cavity oxidative stress and inflammation, consequent cigarettes due to nicotine and acrolein, may be reduced in the presence of green tea polyphenols. In addition, green tea polyphenols can close down halitosis through modification of odorant sulfur components. Usually, green tea defends healthy cells from malignant transformation and locally has the ability to induce apoptosis in oral cancer cells. In unison, there is an increasing implication in the health benefits of green tea in the field of oral health. This review will cover recent findings on the therapeutic properties and anticancer health benefits of green tea.
  13. Ong SL, Nalamolu KR, Lai HY
    Pharmacogn Mag, 2017 Jan;13(Suppl 1):S1-S9.
    PMID: 28479718 DOI: 10.4103/0973-1296.203986
    BACKGROUND: To date, anti-obesity agents based on natural products are tested for their potential using lipase inhibition assay through the interference of hydrolysis of fat by lipase resulting in reduced fat absorption without altering the central mechanisms. Previous screening study had indicated strong anti-obesity potential in Eleusine indica (E. indica), but to date, no pharmacologic studies have been reported so far.

    OBJECTIVE: This study was performed to investigate the lipid-lowering effects of E. indica using both in vitro and in vivo models.

    METHODS: The crude methanolic extract of E. indica was fractionated using hexane (H-Ei), dichloromethane (DCM-Ei), ethyl acetate (EA-Ei), butanol (B-Ei), and water (W-Ei). All the extracts were tested for antilipase activity using porcine pancreatic lipase. Because H-Ei showed the highest inhibition, it was further subjected to chemical profiling using high-performance liquid chromatography. Subsequently, oral toxicity analysis of H-Ei was performed [Organization for Economic Cooperation and Development guidelines using fixed dose procedure (No. 420)]; efficacy analysis was performed using high-fat diet (HFD)-induced hyperlipidemic female Sprague-Dawley rats.

    RESULTS: According to the toxicity and efficacy analyses, H-Ei did not demonstrate any noticeable biochemical toxicity or physiologic abnormalities and did not cause any tissue damage as per histologic analysis. Furthermore, H-Ei significantly reduced body weight and improved serum profile and did not show hepatotoxicity and nephrotoxicity based on the serum profile. Moreover, H-Ei alleviated HFD-induced hepatosteatosis and ameliorated induced adiposity in both visceral and subcutaneous adipose tissue.

    CONCLUSION: Our results demonstrate that H-Ei effectively improved hyperlipidemia. Further studies to explore its possibility as an alternative pharmacologic agent to treat obesity are warranted.

    SUMMARY: Hexane extract of Eleusine indica (H-Ei) showed strong potential in the inhibition of porcine pancreatic lipase (27.01 ± 5.68%).The acute oral toxicity of E. indica hexane extract on animal model falls into Globally Harmonized System Category 5 (low hazard), since mortality, clinical toxicity symptoms, gross pathologic, or histopathologic damage was not observed.The hexane extract of E. indica had significantly reduced the body weight and improved serum lipid profile, with reduction in serum triglycerides, total cholesterol, low-density lipoprotein, and elevation in high-density lipoprotein when comparing against the high-fat diet control group.Microscopic evaluation on histologic slides of liver and adipose tissues suggested that E. indica hexane extract had greatly improved liver steatosis and adipose tissue hypertrophy in high-fat diet control group. Abbreviation used: ALT: Alanine transaminase; AST: Aspartate transaminase; B-Ei: Butanol extract of E. indica; DCM-Ei: Dichloromethane extract of E. indica; EA-Ei: Ethyl acetate extract of E. indica; GHS: Globally Harmonized System; HDL: High-density lipoprotein; H-Ei: Hexane extract of E. indica; HFD: High-fat diet; HPLC: High-performance liquid chromatography; LDL: Low-density lipoprotein; NFD: Normal fed diet; PPL: Porcine pancreatic lipase; SEM: Standard error of mean; SD: Standard deviation; TC: Total cholesterol; TG: Triglycerides; W-Ei: Water extract of E. indica.

  14. Zaid OI, Majid RA, Hasidah MS, Sabariah MN, Al-Zihiry K, Rahi S, et al.
    Pharmacogn Mag, 2017 Jan;13(Suppl 1):S48-S55.
    PMID: 28479726 DOI: 10.4103/0973-1296.203982
    BACKGROUND: Emergence of chloroquine (CQ) resistance among different strains of Plasmodium falciparum is the worst catastrophe that has ever perplexed the dedicated efforts to eradicate malaria. This urged the scientists to search for new alternatives or sensitizers to augment its antiplasmodium effect.

    MATERIALS AND METHOD: In this experiment, the potential of embelin, isolated from Embelia ribes, to inhibit the growth and sensitize CQ action was screened using SYBRE-green-I based drug sensitivity and isobologram assays, respectively. Its effect on red blood cells stability was screened to assess its safety. To explore its molecular mechanism, its effect on plasmodial Hemozoin and the in vitro β-hematin formation was screened as well. Furthermore, its anti-oxidant activity was measured using the conventional in vitro tests and its molecular characters were obtained using Molispiration program.

    RESULTS: The results showed that its anti-plasmodial effect was weaker than CQ but synergism was obtained when they were combined at ratios lower than 5:5 CQ/embelin. Furthermore, β-hematin formation was inhibited by embelin without showing any synergism after mixing with CQ.

    CONCLUSION: Overall, embelin is not ideal to be suggested as a conventional antiplasmodium but it has a potential to ameliorate CQ resistance. Furthermore, its action is not related to its impact on hemozoin formation. Further, investigations are recommended to illustrate its detailed mechanism of action. Abbreviation used: CQ-DV-PBS-HEPES: Chloroquine-Digestive vacuole-Phosphate-buffer-saline-4-(2-hydroxyethyl-1-piperazin-ethan-sulphoni-acid), EDTA: Ethylen-diamin-tetra-acetic-acid, g.m.wt: Gram molecular weight, cMCM: Complete-malaria-culture-medium, Hct: Hematocrite, PRBCs: Parasitized-redblood-cells, nRBCs: Normal-red-blood-cells, RT: Room temperature, IC: Inhibitory concentration, FIC: Fractional inhibitory concentration, iCM: Incomplete-culturemedium, BSA: Bovin serum albumin, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, DPPH: 2,2-diphenyl-1- picrylhydrazy, BHT: Butylatedhydroxyl-toleuen, PSA: Polar surface area, ClogP: Log partition coefficient (octanol/water), GPCR: G-protein-coupled-receptors, DMSO: Dimethylsulphoxide, NaOH: Sodium hydroxide.

  15. Salleh NM, Ismail S, Ibrahim MNM
    Pharmacogn Mag, 2017 Jan;13(Suppl 1):S102-S114.
    PMID: 28479734 DOI: 10.4103/0973-1296.203990
    BACKGROUND: In order to develop oil palm empty fruit bunch (EFB) lignin as a nutraceutical and health supplement, the investigation of its potential in interacting with other drugs via inhibition of drug-metabolizing enzymes (DMEs) would ensure product safety.

    OBJECTIVE: The study was aimed to investigate the in vitro effect of oil palm EFB lignin and its main oxidation compounds on phase II DME UDP-glucuronosyltransferases (UGTs) in rat liver and kidney microsomes.

    MATERIALS AND METHODS: The p-nitrophenol (p-NP) and 4-methylumbelliferone (4-MU) were employed as probe substrates in glucuronidation assays. The effect of soda oil palm EFB lignin on Vmax, Km, CLint, Ki, and mode of inhibition of 4-MU glucuronidation in RLM was also determined.

    RESULTS: The inhibitory potency of oil palm EFB lignin for both p-NP and 4-MU glucuronidation in rat liver microsome (RLM) and rat kidneys microsomes (RKM) was found to be in the rank order of soda > kraft > organosolv. However, the inhibitory potency of its main oxidation compounds were in the rank order of vanillin > syringaldehyde > p-hydroxybenzaldehyde. Soda oil palm EFB lignin exhibited mixed-type inhibition against 4-MU glucuronidation in RLM, showing the change in apparent Vmax and with only a minor effect on Km compared with control.

    CONCLUSIONS: The findings showed that effect of oil palm EFB lignin on both p-NP and 4-MU glucuronidation in RLM and RKM was enhanced by the presence of vanillin as well as flavonoids. Kinetic study showed that soda oil palm EFB lignin exhibited strong inhibition on UGT activity in RLM with mixed-type inhibition mode.

    SUMMARY: The inhibitory potential of oil palm EFB lignin extracts for p-NP and 4-MU glucuronidation in RLM and RKM can be listed in the following rank order: soda > kraft > organosolvThe inhibitory potential of oil palm EFB lignin main oxidation compounds for p-NP and 4-MU glucuronidation in RLM and RKM can be listed in the following rank order: vanillin > syringaldehyde > p-hydroxybenzaldehydeResults suggested that the effect of oil palm EFB lignin on p-NP and 4-MU glucuronidation activity in both RLM and RKM was enhanced by the presence of vanillin as well as total flavonoid contentResults also suggested that oil palm EFB lignin may inhibit glucuronidation of substrate by UGT enzymes, especially UGT1A6, particularly in rat liver Abbreviations used:p-NP: p-Nitrophenol, 4-MU: 4-Methylumbelliferone, EFB: Empty fruit bunch, DME: Drug-metabolizing enzymes, UGT: UDPglucuronosyltransferase, Vmax: Maximal reaction velocity, Km: Michaelis-Menten constant, CLint: Intrinsic clearance, Ki: Dissociation constant of an inhibitor enzyme complex, 4-MUG: 4-Methylumbelliferone glucuronide, DMSO: Dimethyl sulfoxide, IC50: Half maximal inhibitory concentration, p-NPG: p-Nitrophenol glucuronide, RKM: Rat kidneys microsomes, RLM: Rat liver microsome, UDPGA: UDPglucuronic acid, TCA: trichloroacetic acid, MPA: mycophenolic acid.

  16. Inn FX, Ahmed N, Hing EY, Jasman MH
    Urol Ann, 2017 5 10;9(2):194-196.
    PMID: 28479777 DOI: 10.4103/0974-7796.204178
    Tyrosine kinase inhibitor (TKI) and its side effects are well known. However, these are mainly descriptive, with pictorial data lacking. Here, in we report a case of metastatic renal cell carcinoma, treated with TKI, with classic side effects; supplemented with images that demonstrate the adverse effects of the drug. In addition, we discuss and demonstrate the computed tomography changes.
    MeSH terms: Carcinoma, Renal Cell; Kidney Neoplasms; Protein-Tyrosine Kinases; Tomography, X-Ray Computed; Neoplasms, Second Primary; Protein Kinase Inhibitors
  17. Ismail MI, Wong YP, Tan GH, Fam XI
    Urol Ann, 2017 5 10;9(2):197-199.
    PMID: 28479778 DOI: 10.4103/UA.UA_168_16
    Aggressive angiomyxoma (AAM) particularly testicular origin is a rare benign mesenchymal myxoid tumor which is locally aggressive, blatant for local recurrence, and may metastasize. It occurs mostly in females of childbearing age and extremely rare in males. AMM particular testicular origin is not reported in literature yet. This is a 65-year-old man who had a right scrotal swelling. Ultrasound scrotum showed a soft tissue tumor of the right testis. The patient underwent radical right orchidectomy of which histopathologically confirmed to be a paratesticular AAM with clear resection margins. There were no signs of local recurrence or metastasis 2 years postsurgical resection.
    MeSH terms: Aged; Female; Genital Diseases, Male; Humans; Male; Myxoma; Neoplasm Recurrence, Local; Orchiectomy; Scrotum; Soft Tissue Neoplasms; Testis; Margins of Excision
  18. Sarfaraz M, Ahmad MK, Kılıçman A
    J Inequal Appl, 2017;2017(1):81.
    PMID: 28479833 DOI: 10.1186/s13660-017-1351-x
    The resolvent operator approach is applied to address a system of generalized ordered variational inclusions with ⊕ operator in real ordered Banach space. With the help of the resolvent operator technique, Li et al. (J. Inequal. Appl. 2013:514, 2013; Fixed Point Theory Appl. 2014:122, 2014; Fixed Point Theory Appl. 2014:146, 2014; Appl. Math. Lett. 25:1384-1388, 2012; Fixed Point Theory Appl. 2013:241, 2013; Eur. J. Oper. Res. 16(1):1-8, 2011; Fixed Point Theory Appl. 2014:79, 2014; Nonlinear Anal. Forum 13(2):205-214, 2008; Nonlinear Anal. Forum 14: 89-97, 2009) derived an iterative algorithm for approximating a solution of the considered system. Here, we prove an existence result for the solution of the system of generalized ordered variational inclusions and deal with a convergence scheme for the algorithms under some appropriate conditions. Some special cases are also discussed.
  19. Ahmed S, Sulaiman SA, Othman NH
    PMID: 28479926 DOI: 10.1155/2017/5904361
    Breast cancer has been recognized as the leading cause of death in women worldwide. Research has shown the importance of complementary and alternative therapies in cancer. In this study, we investigated the antitumoural therapeutic effects of Malaysian Tualang honey (TH) and Australian/New Zealand Manuka honey (MH) against breast cancer in rats. Thirty syngeneic virgin female Sprague-Dawley (SD) rats were induced by the carcinogen 1-methyl-1-nitrosourea (MNU) 80 mg/kg. The treatment started when first palpable tumour reached 10-12 mm in size by dividing rats into following groups: Group 0 (negative control); Group 1 (positive control); and Groups 2 and 3 which received 1.0 g/kg body weight/day of TH and MH, respectively, for 120 days. The data demonstrate that cancer masses in TH and MH treated groups showed a lower median tumour size, weight, and multiplicity compared with the nontreated positive control (p < 0.05). Treatment also showed a dramatic slower growth rate (up to 70.82%) compared with the nontreated control (0%) (p < 0.05). The antitumoural effect was mediated through modulation of tumour growth, tumour grading, estrogenic activity, and haematological parameters. Our findings demonstrate that systemic administration of TH and MH increases the susceptibility of expression of proapoptotic proteins (Apaf-1, Caspase-9, IFN-γ, IFNGR1, and p53) and decreases the expression of antiapoptotic proteins (TNF-α, COX-2, and Bcl-xL 1) in its mechanism of action. This highlights a potential novel role for TH and MH in alleviating breast cancer.
    MeSH terms: Animals; Australia; Cause of Death; Female; Honey; Humans; Neoplasms; Tumor Necrosis Factor-alpha; Tumor Suppressor Protein p53; Rats, Sprague-Dawley; Leptospermum; Apoptosis Regulatory Proteins; Rats; Cyclooxygenase 2; Caspase 9; Apoptotic Protease-Activating Factor 1; Neoplasm Grading
  20. Ferro EG, Culbert GJ, Wickersham JA, Marcus R, Steffen AD, Pauls HA, et al.
    Open Forum Infect Dis, 2017;4(1):ofw219.
    PMID: 28480230 DOI: 10.1093/ofid/ofw219
    BACKGROUND: Antiretroviral therapy (ART) is recommended for all people living with human immunodeficiency virus (HIV), yet physician attitudes and prescribing behaviors toward members of key risk populations may limit ART access and undermine treatment as prevention strategies.

    METHODS: Physicians in Malaysia (N = 214) who prescribe antiretroviral therapy (ART) responded in an Internet-based survey to hypothetical clinical scenarios of HIV patients, varying by key risk population and CD4+ T-cell count, on whether they would initiate or defer ART compared with a control patient with sexually acquired HIV.

    RESULTS: The proportion of physicians who would defer ART in patients with advanced HIV (CD4 = 17 cells/μL) was significantly higher (P < .0001) for 4 key populations, including people who inject drugs ([PWID] 45.3%) or consume alcohol (42.1%), released prisoners (35.0%), and those lacking social support (26.6%), compared with a control patient (4.2%). People who inject drugs with advanced HIV (CD4 = 17 cells/μL) were 19-fold (adjusted odds ratio [AOR] = 18.9; 95% confidence interval [CI], 9.8-36.5) more likely to have ART deferred compared with the control. This effect was partially mitigated for PWID receiving methadone (AOR = 2.9; 95% CI, 1.5-5.7). At the highest CD4+ T-cell count (CD4 = 470 cells/μL), sex workers (AOR = 0.55; 95% CI, .44-.70) and patients with an HIV-uninfected sexual partner (AOR = 0.43; 95% CI, .34-.57) were significantly less likely to have ART deferred.

    CONCLUSIONS: Physicians who prescribe antiretroviral therapy in Malaysia may defer ART in some key populations including PWID and released prisoners, regardless of CD4+ T-cell count, which may help to explain very low rates of ART coverage among PWID in Malaysia. Reducing HIV incidence and mortality in Malaysia, where HIV is concentrated in PWID and other key populations, requires clinician-level interventions and monitoring physician adherence to international evidence-based treatment guidelines.

External Links