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  1. A community-based prospective cohort study of dengue viral infection in Malaysia: the study protocol
    Jahan NK, Ahmad MP, Dhanoa A, Meng CY, Ming LW, Reidpath DD, et al.
    Infect Dis Poverty, 2016;5(1):76.
    PMID: 27510731 DOI: 10.1186/s40249-016-0172-3
    Globally, dengue infections constitute a significant public health burden. In recent decades, Malaysia has become a dengue hyper-endemic country with the co-circulation of the four dengue virus serotypes. The cyclical dominance of sub-types contributes to a pattern of major outbreaks. The consequences can be observed in the rising incidence of reported dengue cases and dengue related deaths. Understanding the complex interaction of the dengue virus, its human hosts and the mosquito vectors at the community level may help develop strategies for addressing the problem.
  2. Fulltext Seroprevalence of dengue among healthy adults in a rural community in Southern Malaysia: a pilot study
    Dhanoa A, Hassan SS, Jahan NK, Reidpath DD, Fatt QK, Ahmad MP, et al.
    Infect Dis Poverty, 2018 Jan 16;7(1):1.
    PMID: 29335021 DOI: 10.1186/s40249-017-0384-1
    BACKGROUND: The frequency and magnitude of dengue epidemics continue to increase exponentially in Malaysia, with a shift in the age range predominance toward adults and an expansion to rural areas. Despite this, information pertaining to the extent of transmission of dengue virus (DENV) in the rural community is lacking. This community-based pilot study was conducted to establish DENV seroprevalence amongst healthy adults in a rural district in Southern Malaysia, and to identify influencing factors.

    METHODS: In this study undertaken between April and May 2015, a total of 277 adult participants were recruited from households across three localities in the Sungai Segamat subdistrict in Segamat district. Sera were tested for immunoglobulin G (IgG) (Panbio® Dengue Indirect IgG ELISA/high-titer capture) and immunoglobulin M (IgM) (Panbio®) antibodies. The plaque reduction neutralization test (PRNT) was conducted on random samples of IgG-positive sera for further confirmation. Medical history and a recall of previous history of dengue were collected through interviews, whereas sociodemographic information was obtained from an existing database.

    RESULTS: The overall seroprevalence for DENV infection was 86.6% (240/277) (95% CI: 83-91%). Serological evidence of recent infection (IgM/high-titer capture IgG) was noted in 11.2% (31/277) of participants, whereas there was evidence of past infection in 75.5% (209/277) of participants (indirect IgG minus recent infections). The PRNT assay showed that the detected antibodies were indeed specific to DENV. The multivariate analysis showed that the older age group was significantly associated with past DENV infections. Seropositivity increased with age; 48.5% in the age group of <25 years to more than 85% in age group of >45 years (P 

  3. Cultivation of aerobic granular sludge for rubber wastewater treatment
    Rosman NH, Nor Anuar A, Othman I, Harun H, Sulong Abdul Razak MZ, Elias SH, et al.
    Bioresour Technol, 2013 Feb;129:620-3.
    PMID: 23317554 DOI: 10.1016/j.biortech.2012.12.113
    Aerobic granular sludge (AGS) was successfully cultivated at 27±1 °C and pH 7.0±1 during the treatment of rubber wastewater using a sequential batch reactor system mode with complete cycle time of 3 h. Results showed aerobic granular sludge had an excellent settling ability and exhibited exceptional performance in the organics and nutrients removal from rubber wastewater. Regular, dense and fast settling granule (average diameter, 1.5 mm; settling velocity, 33 m h(-1); and sludge volume index, 22.3 mL g(-1)) were developed in a single reactor. In addition, 96.5% COD removal efficiency was observed in the system at the end of the granulation period, while its ammonia and total nitrogen removal efficiencies were up to 94.7% and 89.4%, respectively. The study demonstrated the capabilities of AGS development in a single, high and slender column type-bioreactor for the treatment of rubber wastewater.
  4. Quadrupole-Time-of-Flight Mass Spectrometric Identification of Hemoglobin Subunits α, β, γ and δ in Unknown Peaks of High Performance Liquid Chromatography of Hemoglobin in β-Thalassemias
    Abdullah UYH, Ibrahim HM, Mahmud NB, Salleh MZ, Kek TL, Noorizhab MNFB, et al.
    Hemoglobin, 2019 May;43(3):182-187.
    PMID: 31298599 DOI: 10.1080/03630269.2019.1632893
    This is the first report of quadrupole time-of-flight (Q-TOF) mass spectrometric identification of the hemoglobin (Hb) subunits, α, β, δ and γ peptides, derived from enzymatic-digestion of proteins in the early unknown peaks of the cation exchange chromatography of Hb. The objectives were to identify the unknown high performance liquid chromatography (HPLC) peaks in healthy subjects and in patients with β-thalassemia (β-thal). The results demonstrate the existence of pools of free globin chains in red blood cells (RBCs). The α-, β-, δ- and γ-globin peptides were identified in the unknown HPLC peaks. The quantification and role of the free globin pool in patients with β-thal requires further investigation. Identification of all types of Hb subunits in the retention time (RT) before 1 min. suggests that altered Hbs is the nature of these fast-eluting peaks. Relevancy of thalassemias to the protein-aggregation disorders will require review of the role of free globin in the pathology of the disease.
  5. Fulltext Data on First Record of Brown Morph Banded Langur (Presbytis femoralis), Leucistic Dusky Leaf Monkey (Trachypithecus obscurus) in Malaysia and Review of Morph Diversity in Langur (Colobinae)
    Najmuddin MF, Haris H, Othman N, Zahari F, Mohd-Ridwan AR, Md-Zain BM, et al.
    Data Brief, 2020 Aug;31:105727.
    PMID: 32548216 DOI: 10.1016/j.dib.2020.105727
    Morphism refer to polymorphic species, in which multiple colour variants coexist within a population. Morphism in primates is common and langurs also exhibit certain characteristics of morphism, such as conspicuous natal coats. Banded langurs (Presbytis femoralis) and dusky leaf monkey (Trachypithecus obscurus) exhibits the same characteristics of conspicuous natal coats, but these coats are only limited to infants and changed when they reached adulthood. This article reports the first discovery of rare brown morph of two adult male banded langurs and one leucistic adult female dusky leaf monkey in Malaysia. We also conducted a systematic literature search to review the diversity of morphism in leaf monkey globally.
  6. Fulltext A Biochemical and Pharmacological Characterization of Phospholipase A2 and Metalloproteinase Fractions from Eastern Russell's Viper (Daboia siamensis) Venom: Two Major Components Associated with Acute Kidney Injury
    Chaisakul J, Khow O, Wiwatwarayos K, Rusmili MRA, Prasert W, Othman I, et al.
    Toxins (Basel), 2021 Jul 26;13(8).
    PMID: 34437392 DOI: 10.3390/toxins13080521
    Acute kidney injury (AKI) following Eastern Russell's viper (Daboia siamensis) envenoming is a significant symptom in systemically envenomed victims. A number of venom components have been identified as causing the nephrotoxicity which leads to AKI. However, the precise mechanism of nephrotoxicity caused by these toxins is still unclear. In the present study, we purified two proteins from D. siamensis venom, namely RvPLA2 and RvMP. Protein identification using LCMS/MS confirmed the identity of RvPLA2 to be snake venom phospholipase A2 (SVPLA2) from Thai D. siamensis venom, whereas RvMP exhibited the presence of a factor X activator with two subunits. In vitro and in vivo pharmacological studies demonstrated myotoxicity and histopathological changes of kidney, heart, and spleen. RvPLA2 (3-10 µg/mL) caused inhibition of direct twitches of the chick biventer cervicis muscle preparation. After administration of RvPLA2 or RvMP (300 µg/kg, i.p.) for 24 h, diffuse glomerular congestion and tubular injury with minor loss of brush border were detected in envenomed mice. RvPLA2 and RvMP (300 µg/kg; i.p.) also induced congestion and tissue inflammation of heart muscle as well as diffuse congestion of mouse spleen. This study showed the significant roles of PLA2 and SVMP in snake bite envenoming caused by Thai D. siamensis and their similarities with observed clinical manifestations in envenomed victims. This study also indicated that there is a need to reevaluate the current treatment strategies for Thai D. siamensis envenoming, given the potential for irreversible nephrotoxicity.
  7. Fulltext Pluripotent Human embryonic stem cell derived neural lineages for in vitro modelling of enterovirus 71 infection and therapy
    Yap MS, Tang YQ, Yeo Y, Lim WL, Lim LW, Tan KO, et al.
    Virol J, 2016 Jan 06;13:5.
    PMID: 26738773 DOI: 10.1186/s12985-015-0454-6
    The incidence of neurological complications and fatalities associated with Hand, Foot & Mouth disease has increased over recent years, due to emergence of newly-evolved strains of Enterovirus 71 (EV71). In the search for new antiviral therapeutics against EV71, accurate and sensitive in vitro cellular models for preliminary studies of EV71 pathogenesis is an essential prerequisite, before progressing to expensive and time-consuming live animal studies and clinical trials.
  8. Obstructive sleep apnea among express bus drivers in Malaysia: important indicators for screening
    Yusoff MF, Baki MM, Mohamed N, Mohamed AS, Yunus MR, Ami M, et al.
    Traffic Inj Prev, 2010 Dec;11(6):594-9.
    PMID: 21128189 DOI: 10.1080/15389588.2010.505255
    Obstructive sleep apnea (OSA) has been identified as one of the significant risk factors for motor vehicle crashes (MVCs). In the interest of public safety, this study was conducted to determine the prevalence of OSA and its associated factors among express bus drivers in Malaysia. Identifying factors or conditions related with OSA is very important because they can be used as indicators to subject a person to a confirmatory diagnosis using polysomnography testing.
  9. Fulltext Neural Differentiation of Human Pluripotent Stem Cells for Nontherapeutic Applications: Toxicology, Pharmacology, and In Vitro Disease Modeling
    Yap MS, Nathan KR, Yeo Y, Lim LW, Poh CL, Richards M, et al.
    Stem Cells Int, 2015;2015:105172.
    PMID: 26089911 DOI: 10.1155/2015/105172
    Human pluripotent stem cells (hPSCs) derived from either blastocyst stage embryos (hESCs) or reprogrammed somatic cells (iPSCs) can provide an abundant source of human neuronal lineages that were previously sourced from human cadavers, abortuses, and discarded surgical waste. In addition to the well-known potential therapeutic application of these cells in regenerative medicine, these are also various promising nontherapeutic applications in toxicological and pharmacological screening of neuroactive compounds, as well as for in vitro modeling of neurodegenerative and neurodevelopmental disorders. Compared to alternative research models based on laboratory animals and immortalized cancer-derived human neural cell lines, neuronal cells differentiated from hPSCs possess the advantages of species specificity together with genetic and physiological normality, which could more closely recapitulate in vivo conditions within the human central nervous system. This review critically examines the various potential nontherapeutic applications of hPSC-derived neuronal lineages and gives a brief overview of differentiation protocols utilized to generate these cells from hESCs and iPSCs.
  10. Fulltext Identification of Risk Factors Associated with Resistant Escherichia coli Isolates from Poultry Farms in the East Coast of Peninsular Malaysia: A Cross Sectional Study
    Elmi SA, Simons D, Elton L, Haider N, Abdel Hamid MM, Shuaib YA, et al.
    Antibiotics (Basel), 2021 Jan 26;10(2).
    PMID: 33530462 DOI: 10.3390/antibiotics10020117
    Antimicrobial resistance is of concern to global health security worldwide. We aimed to identify the prevalence, resistance patterns, and risk factors associated with Escherichia coli (E. coli) resistance from poultry farms in Kelantan, Terengganu, and Pahang states of east coast peninsular Malaysia. Between 8 February 2019 and 23 February 2020, a total of 371 samples (cloacal swabs = 259; faecal = 84; Sewage = 14, Tap water = 14) were collected. Characteristics of the sampled farms including management type, biosecurity, and history of disease were obtained using semi-structured questionnaire. Presumptive E. coli isolates were identified based on colony morphology with subsequent biochemical and PCR confirmation. Susceptibility of isolates was tested against a panel of 12 antimicrobials and interpreted alongside risk factor data obtained from the surveys. We isolated 717 E. coli samples from poultry and environmental samples. Our findings revealed that cloacal (17.8%, 46/259), faecal (22.6%, 19/84), sewage (14.3%, 2/14) and tap water (7.1%, 1/14) were significantly (p < 0.003) resistant to at least three classes of antimicrobials. Resistance to tetracycline class were predominantly observed in faecal samples (69%, 58/84), followed by cloacal (64.1%, 166/259), sewage (35.7%, 5/14), and tap water (7.1%, 1/84), respectively. Sewage water (OR = 7.22, 95% CI = 0.95-151.21) had significant association with antimicrobial resistance (AMR) acquisition. Multivariate regression analysis identified that the risk factors including sewage samples (OR = 7.43, 95% CI = 0.96-156.87) and farm size are leading drivers of E. coli antimicrobial resistance in the participating states of east coast peninsular Malaysia. We observed that the resistance patterns of E. coli isolates against 12 panel antimicrobials are generally similar in all selected states of east coast peninsular Malaysia. The highest prevalence of resistance was recorded in tetracycline (91.2%), oxytetracycline (89.1%), sulfamethoxazole/trimethoprim (73.1%), doxycycline (63%), and sulfamethoxazole (63%). A close association between different risk factors and the high prevalence of antimicrobial-resistant E. coli strains reflects increased exposure to resistant bacteria and suggests a concern over rising misuse of veterinary antimicrobials that may contribute to the future threat of emergence of multidrug-resistant pathogen isolates. Public health interventions to limit antimicrobial resistance need to be tailored to local poultry farm practices that affect bacterial transmission.
  11. Effect of newer anti-epileptic drugs (AEDs) on the cognitive status in pentylenetetrazol induced seizures in a zebrafish model
    Choo BKM, Kundap UP, Johan Arief MFB, Kumari Y, Yap JL, Wong CP, et al.
    Prog Neuropsychopharmacol Biol Psychiatry, 2019 06 08;92:483-493.
    PMID: 30844417 DOI: 10.1016/j.pnpbp.2019.02.014
    Epilepsy is marked by seizures that are a manifestation of excessive brain activity and is symptomatically treatable by anti-epileptic drugs (AEDs). Unfortunately, the older AEDs have many side effects, with cognitive impairment being a major side effect that affects the daily lives of people with epilepsy. Thus, this study aimed to determine if newer AEDs (Zonisamide, Levetiracetam, Perampanel, Lamotrigine and Valproic Acid) also cause cognitive impairment, using a zebrafish model. Acute seizures were induced in zebrafish using pentylenetetrazol (PTZ) and cognitive function was assessed using the T-maze test of learning and memory. Neurotransmitter and gene expression levels related to epilepsy as well as learning and memory were also studied to provide a better understanding of the underlying processes. Ultimately, impaired cognitive function was seen in AED treated zebrafish, regardless of whether seizures were induced. A highly significant decrease in γ-Aminobutyric Acid (GABA) and glutamate levels was also discovered, although acetylcholine levels were more variable. The gene expression levels of Brain-Derived Neurotrophic Factor (BDNF), Neuropeptide Y (NPY) and Cyclic Adenosine Monophosphate (CAMP) Responsive Element Binding Protein 1 (CREB-1) were not found to be significantly different in AED treated zebrafish. Based on the experimental results, a decrease in brain glutamate levels due to AED treatment appears to be at least one of the major factors behind the observed cognitive impairment in the treated zebrafish.
  12. Fulltext Antimicrobial Resistance Patterns and Risk Factors Associated with Salmonella spp. Isolates from Poultry Farms in the East Coast of Peninsular Malaysia: A Cross-Sectional Study
    Osman AY, Elmi SA, Simons D, Elton L, Haider N, Khan MA, et al.
    Pathogens, 2021 Sep 09;10(9).
    PMID: 34578192 DOI: 10.3390/pathogens10091160
    The burden of antimicrobial use in agricultural settings is one of the greatest challenges facing global health and food security in the modern era. Malaysian poultry operations are a relevant but understudied component of epidemiology of antimicrobial resistance. We aimed to identify the prevalence, resistance patterns, and risk factors associated with Salmonella isolates from poultry farms in three states of East Coast Peninsular Malaysia. Between 8 February 2019 and 23 February 2020, a total of 371 samples (cloacal swabs = 259; faecal = 84; Sewage = 14, Tap water = 14) was collected from poultry operations. Characteristics of the sampled farms and associated risk factors were obtained using semi-structured questionnaires. Presumptive Salmonella spp. isolates were identified based on colony morphology with subsequent biochemical and PCR confirmation. Susceptibility of isolates was tested against a panel of 12 antimicrobials using disk diffusion method. Our findings revealed that the proportion of Salmonella spp.-positive isolates across sample source were as following: cloacal swab (46.3%, 120/259); faecal (59.5%, 50/84); in tap water (14.3%, 2/14); and in sewage sample (35.7%, 5/14). Isolates from faecal (15.5%, 13/84), cloacal (1.2%, 3/259), and sewage (7.1%, 1/14) samples were significantly resistant to at least five classes of antimicrobials. Resistance to Sulfonamides class (52%, 92/177) was predominantly observed followed by tetracycline (39.5%, 70/177) and aminoglycosides (35.6%, 63/177). Multivariate regression analysis identified intensive management system (OR = 1.55, 95% CI = 1.00-2.40) as a leading driver of antimicrobial resistance (AMR) acquisition. A prevalence of resistance to common antimicrobials was recorded for sulfamethoxazole (33.9%), tetracycline (39.5%), and trimethoprim-sulphamethoxazole (37.9%). A close association between different risk factors and the prevalence of AMR of Salmonella strains suggests a concern over rising misuse of veterinary antimicrobials that may contribute to the emergence and evolution of multidrug-resistant pathogen isolates. One Health approach is recommended to achieve a positive health outcome for all species.
  13. Fulltext A Pharmacological Examination of the Cardiovascular Effects of Malayan Krait (Bungarus candidus) Venoms
    Chaisakul J, Rusmili MR, Hodgson WC, Hatthachote P, Suwan K, Inchan A, et al.
    Toxins (Basel), 2017 03 29;9(4).
    PMID: 28353659 DOI: 10.3390/toxins9040122
    Cardiovascular effects (e.g., tachycardia, hypo- and/or hypertension) are often clinical outcomes of snake envenoming. Malayan krait (Bungarus candidus) envenoming has been reported to cause cardiovascular effects that may be related to abnormalities in parasympathetic activity. However, the exact mechanism for this effect has yet to be determined. In the present study, we investigated thein vivoandin vitrocardiovascular effects ofB. candidusvenoms from Southern (BC-S) and Northeastern (BC-NE) Thailand. SDS-PAGE analysis of venoms showed some differences in the protein profile of the venoms.B. candidusvenoms (50 µg/kg-100 µg/kg, i.v.) caused dose-dependent hypotension in anaesthetised rats. The highest dose caused sudden hypotension (phase I) followed by a return of mean arterial pressure to baseline levels and a decrease in heart rate with transient hypertension (phase II) prior to a small decrease in blood pressure (phase III). Prior administration of monovalent antivenom significantly attenuated the hypotension induced by venoms (100 µg/kg, i.v.). The sudden hypotensive effect of BC-NE venom was abolished by prior administration of hexamethonium (10 mg/kg, i.v.) or atropine (5 mg/kg, i.v.). BC-S and BC-NE venoms (0.1 µg/kg-100 µg/ml) induced concentration-dependent relaxation (EC50= 8 ± 1 and 13 ± 3 µg/mL, respectively) in endothelium-intact aorta. The concentration-response curves were markedly shifted to the right by pre-incubation with L-NAME (0.2 mM), or removal of the endothelium, suggesting that endothelium-derived nitric oxide (NO) is likely to be responsible for venom-induced aortic relaxation. Our data indicate that the cardiovascular effects caused byB. candidusvenoms may be due to a combination of vascular mediators (i.e., NO) and autonomic adaptation via nicotinic and muscarinic acetylcholine receptors.
  14. Fulltext HMGB1: A Common Biomarker and Potential Target for TBI, Neuroinflammation, Epilepsy, and Cognitive Dysfunction
    Paudel YN, Shaikh MF, Chakraborti A, Kumari Y, Aledo-Serrano Á, Aleksovska K, et al.
    Front Neurosci, 2018;12:628.
    PMID: 30271319 DOI: 10.3389/fnins.2018.00628
    High mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein released by glia and neurons upon inflammasome activation and activates receptor for advanced glycation end products (RAGE) and toll-like receptor (TLR) 4 on the target cells. HMGB1/TLR4 axis is a key initiator of neuroinflammation. In recent days, more attention has been paid to HMGB1 due to its contribution in traumatic brain injury (TBI), neuroinflammatory conditions, epileptogenesis, and cognitive impairments and has emerged as a novel target for those conditions. Nevertheless, HMGB1 has not been portrayed as a common prognostic biomarker for these HMGB1 mediated pathologies. The current review discusses the contribution of HMGB1/TLR4/RAGE signaling in several brain injury, neuroinflammation mediated disorders, epileptogenesis and cognitive dysfunctions and in the light of available evidence, argued the possibilities of HMGB1 as a common viable biomarker of the above mentioned neurological dysfunctions. Furthermore, the review also addresses the result of preclinical studies focused on HMGB1 targeted therapy by the HMGB1 antagonist in several ranges of HMGB1 mediated conditions and noted an encouraging result. These findings suggest HMGB1 as a potential candidate to be a common biomarker of TBI, neuroinflammation, epileptogenesis, and cognitive dysfunctions which can be used for early prediction and progression of those neurological diseases. Future study should explore toward the translational implication of HMGB1 which can open the windows of opportunities for the development of innovative therapeutics that could prevent several associated HMGB1 mediated pathologies discussed herein.
  15. Fulltext Variations in neurotoxicity and proteome profile of Malayan krait (Bungarus candidus) venoms
    Rusmili MRA, Othman I, Abidin SAZ, Yusof FA, Ratanabanangkoon K, Chanhome L, et al.
    PLoS One, 2019;14(12):e0227122.
    PMID: 31887191 DOI: 10.1371/journal.pone.0227122
    Malayan krait (Bungarus candidus) is a medically important snake species found in Southeast Asia. The neurotoxic effects of envenoming present as flaccid paralysis of skeletal muscles. It is unclear whether geographical variation in venom composition plays a significant role in the degree of clinical neurotoxicity. In this study, the effects of geographical variation on neurotoxicity and venom composition of B. candidus venoms from Indonesia, Malaysia and Thailand were examined. In the chick biventer cervicis nerve-muscle preparation, all venoms abolished indirect twitches and attenuated contractile responses to nicotinic receptor agonists, with venom from Indonesia displaying the most rapid neurotoxicity. A proteomic analysis indicated that three finger toxins (3FTx), phospholipase A2 (PLA2) and Kunitz-type serine protease inhibitors were common toxin groups in the venoms. In addition, venom from Thailand contained L-amino acid oxidase (LAAO), cysteine rich secretory protein (CRISP), thrombin-like enzyme (TLE) and snake venom metalloproteinase (SVMP). Short-chain post-synaptic neurotoxins were not detected in any of the venoms. The largest quantity of long-chain post-synaptic neurotoxins and non-conventional toxins was found in the venom from Thailand. Analysis of PLA2 activity did not show any correlation between the amount of PLA2 and the degree of neurotoxicity of the venoms. Our study shows that variation in venom composition is not limited to the degree of neurotoxicity. This investigation provides additional insights into the geographical differences in venom composition and provides information that could be used to improve the management of Malayan krait envenoming in Southeast Asia.
  16. Comparison of the neurotoxic and myotoxic effects of two Moroccan scorpion venoms and their neutralization by experimental polyclonal antivenom
    Oukkache N, Ahmad Rusmili MR, Othman I, Ghalim N, Chgoury F, Boussadda L, et al.
    Life Sci, 2015 Mar 1;124:1-7.
    PMID: 25623852 DOI: 10.1016/j.lfs.2014.12.031
    Scorpion venoms contain complex mixtures of molecules, including peptides. These peptides specifically bind to various targets, in particular ion channels. Toxins modulating Na(+), K(+), Ca(2+) and Cl(-) currents were described from venoms. The Androctonus and Buthus geni of scorpions are widely distributed in Morocco. Their stings can cause pain, inflammation, necrosis, muscle paralysis and death. The myotoxicity is predominantly associated with neurotoxic effects and is a cause of mortality and morbidity. In this study, pharmacological effects of venoms were investigated in vitro on neuromuscular transmission.
  17. Fulltext Edible bird's nest ameliorates oxidative stress-induced apoptosis in SH-SY5Y human neuroblastoma cells
    Yew MY, Koh RY, Chye SM, Othman I, Ng KY
    BMC Complement Altern Med, 2014;14:391.
    PMID: 25308934 DOI: 10.1186/1472-6882-14-391
    Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting the senile population with manifestation of motor disability and cognitive impairment. Reactive oxygen species (ROS) is implicated in the progression of oxidative stress-related apoptosis and cell death of the midbrain dopaminergic neurons. Its interplay with mitochondrial functionality constitutes an important aspect of neuronal survival in the perspective of PD. Edible bird's nest (EBN) is an animal-derived natural food product made of saliva secreted by swiftlets from the Aerodamus genus. It contains bioactive compounds which might confer neuroprotective effects to the neurons. Hence this study aims to investigate the neuroprotective effect of EBN extracts in the neurotoxin-induced in vitro PD model.
  18. Proteomic characterization and comparison of Malaysian Bungarus candidus and Bungarus fasciatus venoms
    Rusmili MR, Yee TT, Mustafa MR, Hodgson WC, Othman I
    J Proteomics, 2014 Oct 14;110:129-44.
    PMID: 25154052 DOI: 10.1016/j.jprot.2014.08.001
    Kraits (Bungarus spp.) are highly venomous elapids that are only found in Asia. In the current study, 103 and 86 different proteins were identified from Bungarus candidus and Bungarus fasciatus venoms, respectively. These proteins were classified into 18 different venom protein families. Both venoms were found to contain a high percentage of three finger toxins, phospholipase A2 enzymes and Kunitz-type inhibitors. Smaller number of high molecular weight enzymes such as L-amino acid oxidase, hyaluronidases, and acetylcholinesterase were also detected in the venoms. We also detected some unique proteins that were not known to be present in these venoms. The presence of a natriuretic peptide, vespryn, and serine protease families was detected in B. candidus venom. We also detected the presence of subunit A and B of β-bungarotoxin and α-bungarotoxin which had not been previously found in B. fasciatus venom. Understanding the proteome composition of Malaysian krait species will provide useful information on unique toxins and proteins which are present in the venoms. This knowledge will assist in the management of krait envenoming. In addition, these proteins may have potential use as research tools or as drug-design templates.
  19. Fulltext In-vitro neurotoxicity of two Malaysian krait species (Bungarus candidus and Bungarus fasciatus) venoms: neutralization by monovalent and polyvalent antivenoms from Thailand
    Rusmili MR, Yee TT, Mustafa MR, Othman I, Hodgson WC
    Toxins (Basel), 2014 Mar;6(3):1036-48.
    PMID: 24625762 DOI: 10.3390/toxins6031036
    Bungarus candidus and Bungarus fasciatus are two species of krait found in Southeast Asia. Envenoming by these snakes is often characterized by neurotoxicity and, without treatment, causes considerable morbidity and mortality. In this study, the in vitro neurotoxicity of each species, and the effectiveness of two monovalent antivenoms and a polyvalent antivenom, against the neurotoxic effects of the venoms, were examined in a skeletal muscle preparation. Both venoms caused concentration-dependent inhibition of indirect twitches, and attenuated responses to exogenous nicotinic receptor agonists, in the chick biventer preparation, with B. candidus venom being more potent than B. fasciatus venom. SDS-PAGE and western blot analysis indicated different profiles between the venoms. Despite these differences, most proteins bands were recognized by all three antivenoms. Antivenom, added prior to the venoms, attenuated the neurotoxic effect of the venoms. Interestingly, the respective monovalent antivenoms did not neutralize the effects of the venom from the other Bungarus species indicating a relative absence of cross-neutralization. Addition of a high concentration of polyvalent antivenom, at the t90 time point after addition of venom, partially reversed the neurotoxicity of B. fasciatus venom but not B. candidus venom. The monovalent antivenoms had no significant effect when added at the t90 time point. This study showed that B. candidus and B. fasciatus venoms display marked in vitro neurotoxicity in the chick biventer preparation and administration of antivenoms at high dose is necessary to prevent or reverse neurotoxicity.
  20. Proteomic analysis of Moroccan cobra Naja haje legionis venom using tandem mass spectrometry
    Malih I, Ahmad rusmili MR, Tee TY, Saile R, Ghalim N, Othman I
    J Proteomics, 2014 Jan 16;96:240-52.
    PMID: 24269350 DOI: 10.1016/j.jprot.2013.11.012
    The proteome of the venom of Naja haje legionis, the only medically important elapid species in Morocco, has been elucidated by using a combination of proteomic techniques that includes size exclusion chromatography, reverse-phase HPLC, Tricine/SDS-Page, tryptic digestion, Q-TOF tandem mass spectrometry and database search. The sequence analysis of venom fractions revealed a highly complex venom proteome which counts a total of 76 proteins identified from database that can be assigned into 9 proteins families. We report the identification of: cobra venom factor (CVF), l-amino-acid oxidases (LAAO), acetylcholinesterase (AChE), snake venom metalloproteinases (SVMP), cysteine rich secretory proteins (CRISP), venom nerve growth factor (vNGF), phospholipases A2 (PLA2), vespryns, kunitz-type inhibitor, short neurotoxins, long neurotoxins, weak neurotoxins, neurotoxin like proteins, muscarinic toxins, cardiotoxins and cytotoxins. Comparison of these proteins showed high sequence homology with proteins from other African and Asian cobras. Further works are needed to assess the contribution of individual toxins in venom toxicity.
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