Displaying publications 1 - 20 of 69 in total

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  1. A pilot project on hospital-based universal newborn hearing screening: lessons learned
    Mukari SZ, Tan KY, Abdullah A
    Int J Pediatr Otorhinolaryngol, 2006 May;70(5):843-51.
    PMID: 16246430
    This paper reports the performance of a newly implemented hospital-based universal newborn hearing screening programme and the challenges to the effective implementation.
  2. Application of biochemical products as a bioremediation technique for domestic sewage treatment plants
    Salmiati, Salim MR, Hassan RM, Tan KY
    Water Sci Technol, 2007;56(7):33-40.
    PMID: 17951865
    Biochemical products have been widely used for treatment of various types of wastewater. The treatment processes with the addition of biochemical products are quite attractive because of their simplicity, minimal use of equipment, they are environmentally friendly and are suitable for the removal of organic pollutants. The purpose of these products is to enhance the activities of beneficial microbes in order to improve treatment performance. This study was carried out to determine the potential of applying biochemical products in assisting and improving the performance of sewage treatment plants. In this study, four biochemical products, namely: Zeolite, Bio-C, Eco-B and Was-D, were applied to the sewage treatment plant. Analyses were carried out on several water quality parameters such as biochemical oxygen demand (BOD), chemical oxygen demand (COD), suspended solids (SS), oil & grease (O&G), phosphorus (P), ammoniacal nitrogen (AN) and sludge thickness (ST). From the results obtained, it can be seen that the overall performance of the treatment plant improved with most of the parameters studied were found to fulfill the DOE Standard B requirements. The performance of Bio-C was found to give better results than other products.
  3. Proteomic characterization of venom of the medically important Southeast Asian Naja sumatrana (Equatorial spitting cobra)
    Yap MK, Fung SY, Tan KY, Tan NH
    Acta Trop, 2014 May;133:15-25.
    PMID: 24508616 DOI: 10.1016/j.actatropica.2014.01.014
    The proteome of Naja sumatrana (Equatorial spitting cobra) venom was investigated by shotgun analysis and a combination of ion-exchange chromatography and reverse phase HPLC. Shotgun analysis revealed the presence of 39 proteins in the venom while the chromatographic approach identified 37 venom proteins. The results indicated that, like other Asiatic cobra venoms, N. sumatrana contains large number of three finger toxins and phospholipases A2, which together constitute 92.1% by weight of venom protein. However, only eight of the toxins can be considered as major venom toxins. These include two phospholipases A2, three neurotoxins (two long neurotoxins and a short neurotoxin) and three cardiotoxins. The eight major toxins have relative abundance of 1.6-27.2% venom proteins and together account for 89.8% (by weight) of total venom protein. Other venom proteins identified include Zn-metalloproteinase-disintegrin, Thaicobrin, CRISP, natriuretic peptide, complement depleting factors, cobra venom factors, venom nerve growth factor and cobra serum albumin. The proteome of N. sumatrana venom is similar to proteome of other Asiatic cobra venoms but differs from that of African spitting cobra venom. Our results confirm that the main toxic action of N. sumatrana venom is neurotoxic but the large amount of cardiotoxins and phospholipases A2 are likely to contribute significantly to the overall pathophysiological action of the venom. The differences in toxin distribution between N. sumatrana venom and African spitting cobra venoms suggest possible differences in the pathophysiological actions of N. sumatrana venom and the African spitting cobra venoms, and explain why antivenom raised against Asiatic cobra venom is not effective against African spitting cobra venoms.
  4. Fulltext Antivenom cross-neutralization of the venoms of Hydrophis schistosus and Hydrophis curtus, two common sea snakes in Malaysian waters
    Tan CH, Tan NH, Tan KY, Kwong KO
    Toxins (Basel), 2015 Feb;7(2):572-81.
    PMID: 25690691 DOI: 10.3390/toxins7020572
    Sea snake envenomation is a serious occupational hazard in tropical waters. In Malaysia, the beaked sea snake (Hydrophis schistosus, formerly known as Enhydrina schistosa) and the spine-bellied sea snake (Hydrophis curtus, formerly known as Lapemis curtus or Lapemis hardwickii) are two commonly encountered species. Australian CSL sea snake antivenom is the definitive treatment for sea snake envenomation; it is unfortunately extremely costly locally and is not widely available or adequately stocked in local hospitals. This study investigated the cross-neutralizing potential of three regionally produced anti-cobra antivenoms against the venoms of Malaysian H. schistosus and H. curtus. All three antivenoms conferred paraspecific protection from sea snake venom lethality in mice, with potency increasing in the following order: Taiwan bivalent antivenom < Thai monocled cobra monovalent antivenom < Thai neuro polyvalent antivenom (NPAV). NPAV demonstrated cross-neutralizing potencies of 0.4 mg/vial for H. schistosus venom and 0.8 mg/vial for H. curtus, which translates to a dose of less than 20 vials of NPAV to neutralize an average amount of sea snake venom per bite (inferred from venom milking). The cross-neutralization activity was supported by ELISA cross-reactivity between NPAV and the venoms of H. schistosus (58.4%) and H. curtus (70.4%). These findings revealed the potential of NPAV as a second-line treatment for sea snake envenomation in the region. Further profiling of the cross-neutralization activity should address the antivenomic basis using purified toxin-based assays.
  5. Venomics, lethality and neutralization of Naja kaouthia (monocled cobra) venoms from three different geographical regions of Southeast Asia
    Tan KY, Tan CH, Fung SY, Tan NH
    J Proteomics, 2015 Apr 29;120:105-25.
    PMID: 25748141 DOI: 10.1016/j.jprot.2015.02.012
    Previous studies showed that venoms of the monocled cobra, Naja kaouthia from Thailand and Malaysia are substantially different in their median lethal doses. The intraspecific venom variations of N. kaouthia, however, have not been fully elucidated. Here we investigated the venom proteomes of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V) through reverse-phase HPLC, SDS-PAGE and tandem mass spectrometry. The venom proteins comprise 13 toxin families, with three-finger toxins being the most abundant (63-77%) and the most varied (11-18 isoforms) among the three populations. NK-T has the highest content of neurotoxins (50%, predominantly long neurotoxins), followed by NK-V (29%, predominantly weak neurotoxins and some short neurotoxins), while NK-M has the least (18%, some weak neurotoxins but less short and long neurotoxins). On the other hand, cytotoxins constitute the main bulk of toxins in NK-M and NK-V venoms (up to 45% each), but less in NK-T venom (27%). The three venoms show different lethal potencies that generally reflect the proteomic findings. Despite the proteomic variations, the use of Thai monovalent and Neuro polyvalent antivenoms for N. kaouthia envenomation in the three regions is appropriate as the different venoms were neutralized by the antivenoms albeit at different degrees of effectiveness.
  6. Venomics of the beaked sea snake, Hydrophis schistosus: A minimalist toxin arsenal and its cross-neutralization by heterologous antivenoms
    Tan CH, Tan KY, Lim SE, Tan NH
    J Proteomics, 2015 Aug 3;126:121-30.
    PMID: 26047715 DOI: 10.1016/j.jprot.2015.05.035
    The venom proteome of Hydrophis schistosus (syn: Enhydrina schistosa) captured in Malaysian waters was investigated using reverse-phase HPLC, SDS-PAGE and high-resolution liquid chromatography-tandem mass spectrometry. The findings revealed a minimalist profile with only 18 venom proteins. These proteins belong to 5 toxin families: three-finger toxin (3FTx), phospholipase A2 (PLA2), cysteine-rich secretory protein (CRISP), snake venom metalloprotease (SVMP) and L-amino acid oxidase (LAAO). The 3FTxs (3 short neurotoxins and 4 long neurotoxins) constitute 70.5% of total venom protein, 55.8% being short neurotoxins and 14.7% long neurotoxins. The PLA2 family consists of four basic (21.4%) and three acidic (6.1%) isoforms. The minor proteins include one CRISP (1.3%), two SVMPs (0.5%) and one LAAO (0.2%). This is the first report of the presence of long neurotoxins, CRISP and LAAO in H. schistosus venom. The neurotoxins and the basic PLA2 are highly lethal in mice with an intravenous median lethal dose of <0.2 μg/g. Cross-neutralization by heterologous elapid antivenoms (Naja kaouthia monovalent antivenom and Neuro polyvalent antivenom) was moderate against the long neurotoxin and basic PLA2, but weak against the short neurotoxin, indicating that the latter is the limiting factor to be overcome for improving the antivenom cross-neutralization efficacy.
  7. Health claims on food products in Southeast Asia: regulatory frameworks, barriers, and opportunities
    Tan KY, van der Beek EM, Chan MY, Zhao X, Stevenson L
    Nutr Rev, 2015 Sep;73(9):634-41.
    PMID: 26269489 DOI: 10.1093/nutrit/nuv029
    The Association of Southeast Asian Nations aims to act as a single market and allow free movement of goods, services, and manpower. The purpose of this article is to present an overview of the current regulatory framework for health claims in Southeast Asia and to highlight the current barriers and opportunities in the regulatory frameworks in the Association of Southeast Asian Nations. To date, 5 countries in Southeast Asia, i.e., Indonesia, Malaysia, the Philippines, Singapore, and Thailand, have regulations and guidelines to permit the use of health claims on food products. There are inconsistencies in the regulations and the types of evidence required for health claim applications in these countries. A clear understanding of the regulatory frameworks in these countries may help to increase trade in this fast-growing region and to provide direction for the food industry and the regulatory community to develop and market food products with better nutritional quality tailored to the needs of Southeast Asian consumers.
  8. Functional venomics of the Sri Lankan Russell's viper (Daboia russelii) and its toxinological correlations
    Tan NH, Fung SY, Tan KY, Yap MK, Gnanathasan CA, Tan CH
    J Proteomics, 2015 Oct 14;128:403-23.
    PMID: 26342672 DOI: 10.1016/j.jprot.2015.08.017
    The venom proteome (venomics) of the Sri Lankan Daboia russelii was elucidated using 1D SDS PAGE nano-ESI-LCMS/MS shotgun proteomics. A total of 41 different venom proteins belonging to 11 different protein families were identified. The four main protein families are phospholipase A2 (PLA2, 35.0%), snaclec (SCL, 22.4%, mainly platelet aggregation inhibitors), snake venom serine proteinase (SVSP, 16.0%, mainly Factor V activating enzyme) and snake venom metalloproteinase (SVMP, 6.9%, mainly heavy chain of Factor X activating enzyme). Other protein families that account for more than 1% of the venom protein include l-amino acid oxidase (LAAO, 5.2%), Kunitz-type serine proteinase inhibitor (KSPI, 4.6%), venom nerve growth factor (VNGF. 3.5%), 5'-nucleotidase (5'NUC, 3.0%), cysteine-rich secretory protein (CRISP, 2.0%) and phosphodiesterase (PDE, 1.3%). The venom proteome is consistent with the enzymatic and toxic activities of the venom, and it correlates with the clinical manifestations of Sri Lankan D. russelii envenomation which include hemorrhage, coagulopathy, renal failure, neuro-myotoxicity and intravascular hemolysis. The venom exhibited remarkable presypnatic neurotoxicity presumably due to the action of basic PLA2 in high abundance (35.0%). Besides, SCLs, Factor X activating enzymes (SVMPs), SVSPs, and LAAOs are potential hemotoxins (50.5%), contributing to coagulopathy and hemorrhagic syndrome in Sri Lankan D. russelii envenomation.
  9. Fulltext Venom-gland transcriptome and venom proteome of the Malaysian king cobra (Ophiophagus hannah)
    Tan CH, Tan KY, Fung SY, Tan NH
    BMC Genomics, 2015;16:687.
    PMID: 26358635 DOI: 10.1186/s12864-015-1828-2
    The king cobra (Ophiophagus hannah) is widely distributed throughout many parts of Asia. This study aims to investigate the complexity of Malaysian Ophiophagus hannah (MOh) venom for a better understanding of king cobra venom variation and its envenoming pathophysiology. The venom gland transcriptome was investigated using the Illumina HiSeq™ platform, while the venom proteome was profiled by 1D-SDS-PAGE-nano-ESI-LCMS/MS.
  10. Fulltext Detection of Prosthetic Knee Movement Phases via In-Socket Sensors: A Feasibility Study
    El-Sayed AM, Hamzaid NA, Tan KY, Abu Osman NA
    ScientificWorldJournal, 2015;2015:923286.
    PMID: 25945365 DOI: 10.1155/2015/923286
    This paper presents an approach of identifying prosthetic knee movements through pattern recognition of mechanical responses at the internal socket's wall. A quadrilateral double socket was custom made and instrumented with two force sensing resistors (FSR) attached to specific anterior and posterior sites of the socket's wall. A second setup was established by attaching three piezoelectric sensors at the anterior distal, anterior proximal, and posterior sites. Gait cycle and locomotion movements such as stair ascent and sit to stand were adopted to characterize the validity of the technique. FSR and piezoelectric outputs were measured with reference to the knee angle during each phase. Piezoelectric sensors could identify the movement of midswing and terminal swing, pre-full standing, pull-up at gait, sit to stand, and stair ascent. In contrast, FSR could estimate the gait cycle stance and swing phases and identify the pre-full standing at sit to stand. FSR showed less variation during sit to stand and stair ascent to sensitively represent the different movement states. The study highlighted the capacity of using in-socket sensors for knee movement identification. In addition, it validated the efficacy of the system and warrants further investigation with more amputee subjects and different sockets types.
  11. Fulltext Chick embryo chorioallantoic membrane (CAM): an alternative predictive model in acute toxicological studies for anti-cancer drugs
    Kue CS, Tan KY, Lam ML, Lee HB
    Exp Anim, 2015;64(2):129-38.
    PMID: 25736707 DOI: 10.1538/expanim.14-0059
    The chick embryo chorioallantoic membrane (CAM) is a preclinical model widely used for vascular and anti-vascular effects of therapeutic agents in vivo. In this study, we examine the suitability of CAM as a predictive model for acute toxicology studies of drugs by comparing it to conventional mouse and rat models for 10 FDA-approved anticancer drugs (paclitaxel, carmustine, camptothecin, cyclophosphamide, vincristine, cisplatin, aloin, mitomycin C, actinomycin-D, melphalan). Suitable formulations for intravenous administration were determined before the average of median lethal dose (LD50) and median survival dose (SD(50)) in the CAM were measured and calculated for these drugs. The resultant ideal LD(50) values were correlated to those reported in the literature using Pearson's correlation test for both intravenous and intraperitoneal routes of injection in rodents. Our results showed moderate correlations (r(2)=0.42 - 0.68, P<0.005-0.05) between the ideal LD(50) values obtained using the CAM model with LD(50) values from mice and rats models for both intravenous and intraperitoneal administrations, suggesting that the chick embryo may be a suitable alternative model for acute drug toxicity screening before embarking on full toxicological investigations in rodents in development of anticancer drugs.
  12. Fulltext A Simple and Novel Strategy for the Production of a Pan-specific Antiserum against Elapid Snakes of Asia
    Ratanabanangkoon K, Tan KY, Eursakun S, Tan CH, Simsiriwong P, Pamornsakda T, et al.
    PLoS Negl Trop Dis, 2016 Apr;10(4):e0004565.
    PMID: 27058956 DOI: 10.1371/journal.pntd.0004565
    Snakebite envenomation is a serious medical problem in many tropical developing countries and was considered by WHO as a neglected tropical disease. Antivenom (AV), the rational and most effective treatment modality, is either unaffordable and/or unavailable in many affected countries. Moreover, each AV is specific to only one (monospecific) or a few (polyspecific) snake venoms. This demands that each country to prepare AV against its local snake venoms, which is often not feasible. Preparation of a 'pan-specific' AV against many snakes over a wide geographical area in some countries/regions has not been possible. If a 'pan-specific' AV effective against a variety of snakes from many countries could be prepared, it could be produced economically in large volume for use in many countries and save many lives. The aim of this study was to produce a pan-specific antiserum effective against major medically important elapids in Asia. The strategy was to use toxin fractions (TFs) of the venoms in place of crude venoms in order to reduce the number of antigens the horses were exposed to. This enabled inclusion of a greater variety of elapid venoms in the immunogen mix, thus exposing the horse immune system to a diverse repertoire of toxin epitopes, and gave rise to antiserum with wide paraspecificity against elapid venoms. Twelve venom samples from six medically important elapid snakes (4 Naja spp. and 2 Bungarus spp.) were collected from 12 regions/countries in Asia. Nine of these 12 venoms were ultra-filtered to remove high molecular weight, non-toxic and highly immunogenic proteins. The remaining 3 venoms were not ultra-filtered due to limited amounts available. The 9 toxin fractions (TFs) together with the 3 crude venoms were emulsified in complete Freund's adjuvant and used to immunize 3 horses using a low dose, low volume, multisite immunization protocol. The horse antisera were assayed by ELISA and by in vivo lethality neutralization in mice. The findings were: a) The 9 TFs were shown to contain all of the venom toxins but were devoid of high MW proteins. When these TFs, together with the 3 crude venoms, were used as the immunogen, satisfactory ELISA antibody titers against homologous/heterologous venoms were obtained. b) The horse antiserum immunologically reacted with and neutralized the lethal effects of both the homologous and the 16 heterologous Asian/African elapid venoms tested. Thus, the use of TFs in place of crude venoms and the inclusion of a variety of elapid venoms in the immunogen mix resulted in antiserum with wide paraspecificity against elapid venoms from distant geographic areas. The antivenom prepared from this antiserum would be expected to be pan-specific and effective in treating envenomations by most elapids in many Asian countries. Due to economies of scale, the antivenom could be produced inexpensively and save many lives. This simple strategy and procedure could be readily adapted for the production of pan-specific antisera against elapids of other continents.
  13. Revisiting Notechis scutatus venom: on shotgun proteomics and neutralization by the "bivalent" Sea Snake Antivenom
    Tan CH, Tan KY, Tan NH
    J Proteomics, 2016 07 20;144:33-8.
    PMID: 27282922 DOI: 10.1016/j.jprot.2016.06.004
    Recent advances in proteomics enable deep profiling of the compositional details of snake venoms for improved understanding on envenomation pathophysiology and immunological neutralization. In this study, the venom of Australian tiger snake (Notechis scutatus) was trypsin-digested in solution and subjected to nano-ESI-LCMS/MS. Applying a relative quantitative proteomic approach, the findings revealed a proteome comprising 42 toxin subtypes clustered into 12 protein families. Phospholipases A2 constitute the most abundant toxins (74.5% of total venom proteins) followed by Kunitz serine protease inhibitors (6.9%), snake venom serine proteases (5.9%), alpha-neurotoxins (5.6%) and several toxins of lower abundance. The proteome correlates with N. scutatus envenoming effects including pre-synaptic and post-synaptic neurotoxicity and consumptive coagulopathy. The venom is highly lethal in mice (intravenous median lethal dose=0.09μg/g). BioCSL Sea Snake Antivenom, raised against the venoms of beaked sea snake (Hydrophis schistosus) and N. scutatus (added for enhanced immunogenicity), neutralized the lethal effect of N. scutatus venom (potency=2.95mg/ml) much more effectively than the targeted H.schistosus venom (potency=0.48mg/ml). The combined venom immunogen may have improved the neutralization against phospholipases A2 which are abundant in both venoms, but not short-neurotoxins which are predominant only in H. schistosus venom.

    SIGNIFICANCE: A shotgun proteomic approach adopted in this study revealed the compositional details of the venom of common tiger snake from Australia, Notechis scutatus. The proteomic findings provided additional information on the relative abundances of toxins and the detection of proteins of minor expression unreported previously. The potent lethal effect of the venom was neutralized by bioCSL Sea Snake Antivenom, an anticipated finding due to the fact that the Sea Snake Antivenom is actually bivalent in nature, being raised against a mix of venoms of the beaked sea snake (Hydrophis schistosus) and N. scutatus. However, it is surprising to note that bioCSL Sea Snake Antivenom neutralized N. scutatus venom much more effectively compared to the targeted sea snake venom by a marked difference in potency of approximately 6-fold. This phenomenon may be explained by the main difference in the proteomes of the two venoms, where H. schistosus venom is dominated by short-neurotoxins in high abundance - this is a poorly immunogenic toxin group that has been increasingly recognized in the venoms of a few cobras. Further investigations should be directed toward strategies to improve the neutralization of short-neurotoxins, in line with the envisioned production of an effective pan-regional elapid antivenom.

  14. Genus Calliophis of Asiatic coral snakes: A deficiency of venom cross-reactivity and neutralization against seven regional elapid antivenoms
    Tan CH, Liew JL, Tan KY, Tan NH
    Toxicon, 2016 Oct;121:130-133.
    PMID: 27616455 DOI: 10.1016/j.toxicon.2016.09.003
    Venoms of Calliophis bivirgata and Calliophis intestinalis exhibited moderate binding activities toward Neuro Bivalent Antivenom (Taiwan) but not the other six elapid monovalent or bivalent antivenoms available in the region. All antivenoms failed to neutralize C. bivirgata venom lethality in mice. The findings indicate the need to validate antivenom cross-reactivity with in vivo cross-neutralization, and imply that distinct antigens of Calliophis venoms should be incorporated in the production of a pan-regional poly-specific antivenom.
  15. Fulltext Assessing SABU (Serum Anti Bisa Ular), the sole Indonesian antivenom: A proteomic analysis and neutralization efficacy study
    Tan CH, Liew JL, Tan KY, Tan NH
    Sci Rep, 2016 11 21;6:37299.
    PMID: 27869134 DOI: 10.1038/srep37299
    Serum Anti Ular Bisa (SABU) is the only snake antivenom produced locally in Indonesia; however, its effectiveness has not been rigorously evaluated. This study aimed to assess the protein composition and neutralization efficacy of SABU. SDS polyacrylamide gel electrophoresis, size-exclusion liquid chromatography and shotgun proteomics revealed that SABU consists of F(ab')2 but a significant amount of dimers, protein aggregates and contaminant albumins. SABU moderately neutralized Calloselasma rhodostoma venom (potency of 12.7 mg venom neutralized per ml antivenom, or 121.8 mg venom per g antivenom protein) and Bungarus fasciatus venom (0.9 mg/ml; 8.5 mg/g) but it was weak against the venoms of Naja sputatrix (0.3 mg/ml; 2.9 mg/g), Naja sumatrana (0.2 mg/ml; 1.8 mg/g) and Bungarus candidus (0.1 mg/ml; 1.0 mg/g). In comparison, NPAV, the Thai Neuro Polyvalent Antivenom, outperformed SABU with greater potencies against the venoms of N. sputatrix (0.6 mg/ml; 8.3 mg/g), N. sumatrana (0.5 mg/ml; 7.1 mg/g) and B. candidus (1.7 mg/ml; 23.2 mg/g). The inferior efficacy of SABU implies that a large antivenom dose is required clinically for effective treatment. Besides, the antivenom contains numerous impurities e.g., albumins that greatly increase the risk of hypersensitivity. Together, the findings indicate that the production of SABU warrants further improvement.
  16. Geographical venom variations of the Southeast Asian monocled cobra (Naja kaouthia): venom-induced neuromuscular depression and antivenom neutralization
    Tan KY, Tan CH, Sim SM, Fung SY, Tan NH
    Comp Biochem Physiol C Toxicol Pharmacol, 2016 Jul-Aug;185-186:77-86.
    PMID: 26972756 DOI: 10.1016/j.cbpc.2016.03.005
    The Southeast Asian monocled cobras (Naja kaouthia) exhibit geographical variations in their venom proteomes, especially on the composition of neurotoxins. This study compared the neuromuscular depressant activity of the venoms of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V), and the neutralization of neurotoxicity by a monospecific antivenom. On chick biventer cervicis nerve-muscle preparation, all venoms abolished the indirect twitches, with NK-T venom being the most potent (shortest t90, time to 90% twitch inhibition), followed by NK-V and NK-M. Acetylcholine and carbachol failed to reverse the blockade, indicating irreversible/pseudo-irreversible post-synaptic neuromuscular blockade. KCl restored the twitches variably (NK-M preparation being the least responsive), consistent with different degree of muscle damage. The findings support that NK-T venom has the most abundant curarimimetic alpha-neurotoxins, while NK-M venom contains more tissue-damaging cytotoxins. Pre-incubation of tissue with N. kaouthia monovalent antivenom (NKMAV) prevented venom-induced twitch depression, with the NK-T preparation needing the largest antivenom dose. NKMAV added after the onset of neuromuscular depression could only halt the inhibitory progression but failed to restore full contraction. The findings highlight the urgency of early antivenom administration to sequester as much circulating neurotoxins as possible, thereby hastening toxin elimination from the circulation. In envenomed mice, NKMAV administered upon the first neurological sign neutralized the neurotoxic effect, with the slowest full recovery noticed in the NK-T group. This is consistent with the high abundance of neurotoxins in the NK-T venom, implying that a larger amount or repeated dosing of NKMAV may be required in NK-T envenomation.
  17. Fulltext PGD: a pangolin genome hub for the research community
    Tan TK, Tan KY, Hari R, Mohamed Yusoff A, Wong GJ, Siow CC, et al.
    Database (Oxford), 2016;2016.
    PMID: 27616775 DOI: 10.1093/database/baw063
    Pangolins (order Pholidota) are the only mammals covered by scales. We have recently sequenced and analyzed the genomes of two critically endangered Asian pangolin species, namely the Malayan pangolin (Manis javanica) and the Chinese pangolin (Manis pentadactyla). These complete genome sequences will serve as reference sequences for future research to address issues of species conservation and to advance knowledge in mammalian biology and evolution. To further facilitate the global research effort in pangolin biology, we developed the Pangolin Genome Database (PGD), as a future hub for hosting pangolin genomic and transcriptomic data and annotations, and with useful analysis tools for the research community. Currently, the PGD provides the reference pangolin genome and transcriptome data, gene sequences and functional information, expressed transcripts, pseudogenes, genomic variations, organ-specific expression data and other useful annotations. We anticipate that the PGD will be an invaluable platform for researchers who are interested in pangolin and mammalian research. We will continue updating this hub by including more data, annotation and analysis tools particularly from our research consortium.Database URL: http://pangolin-genome.um.edu.my.
  18. Fulltext Venomics of Tropidolaemus wagleri, the sexually dimorphic temple pit viper: Unveiling a deeply conserved atypical toxin arsenal
    Tan CH, Tan KY, Yap MK, Tan NH
    Sci Rep, 2017 02 27;7:43237.
    PMID: 28240232 DOI: 10.1038/srep43237
    Tropidolaemus wagleri (temple pit viper) is a medically important snake in Southeast Asia. It displays distinct sexual dimorphism and prey specificity, however its venomics and inter-sex venom variation have not been thoroughly investigated. Applying reverse-phase HPLC, we demonstrated that the venom profiles were not significantly affected by sex and geographical locality (Peninsular Malaya, insular Penang, insular Sumatra) of the snakes. Essentially, venoms of both sexes share comparable intravenous median lethal dose (LD50) (0.56-0.63 μg/g) and cause neurotoxic envenomation in mice. LCMS/MS identified six waglerin forms as the predominant lethal principles, comprising 38.2% of total venom proteins. Fourteen other toxin-protein families identified include phospholipase A2, serine proteinase, snaclec and metalloproteinase. In mice, HPLC fractions containing these proteins showed insignificant contribution to the overall venom lethality. Besides, the unique elution pattern of approximately 34.5% of non-lethal, low molecular mass proteins (3-5 kDa) on HPLC could be potential biomarker for this primitive crotalid species. Together, the study unveiled the venom proteome of T. wagleri that is atypical among many pit vipers as it comprises abundant neurotoxic peptides (waglerins) but little hemotoxic proteinases. The findings also revealed that the venom is relatively well conserved intraspecifically despite the drastic morphological differences between sexes.
  19. Fulltext Assessment of Anteroposterior Subpedicular Approach and Oblique Scotty Dog Subpedicular Approach for Selective Nerve Root Block
    Kaliya-Perumal AK, Yeh YC, Luo CA, Joey-Tan KY
    Clin Orthop Surg, 2017 Mar;9(1):71-76.
    PMID: 28261430 DOI: 10.4055/cios.2017.9.1.71
    BACKGROUND: The technique used to administer a selective nerve root block (SNRB) varies depending on individual expertise. Both the anteroposterior (AP) subpedicular approach and oblique Scotty dog subpedicular approach are widely practiced. However, the literature does not provide a clear consensus regarding which approach is more suitable. Hence, we decided to analyse the procedural parameters and clinical outcomes following SNRBs using these two approaches.

    METHODS: Patients diagnosed with a single lumbar herniated intervertebral disc (HIVD) refractory to conservative management but not willing for immediate surgery were selected for a prospective nonrandomized comparative study. An SNRB was administered as a therapeutic alternative using the AP subpedicular approach in one group (n = 25; mean age, 45 ± 5.4 years) and the oblique Scotty dog subpedicular approach in the other group (n = 22; mean age, 43.8 ± 4.7 years). Results were compared in terms of the duration of the procedure, the number of C-arm exposures, accuracy, pain relief, functional outcome and the duration of relief.

    RESULTS: Our results suggest that the oblique Scotty dog subpedicular approach took a significantly longer duration (p = 0.02) and a greater number of C-arm exposures (p = 0.001). But, its accuracy of needle placement was 95.5% compared to only 72% using the AP subpedicular approach (p = 0.03). There was no significant difference in terms of clinical outcomes between these approaches.

    CONCLUSIONS: The AP subpedicular approach was simple and facile, but the oblique Scotty dog subpedicular approach was more accurate. However, a brief window period of pain relief was achieved irrespective of the approaching technique used.

  20. Fulltext A novel in vitro potency assay of antisera against Thai Naja kaouthia based on nicotinic acetylcholine receptor binding
    Ratanabanangkoon K, Simsiriwong P, Pruksaphon K, Tan KY, Eursakun S, Tan CH, et al.
    Sci Rep, 2017 08 17;7(1):8545.
    PMID: 28819275 DOI: 10.1038/s41598-017-08962-3
    Snake envenomation is an important medical problem. One of the hurdles in antivenom development is the in vivo assay of antivenom potency which is expensive, gives variable results and kills many animals. We report a novel in vitro assay involving the specific binding of the postsynaptic neurotoxins (PSNTs) of elapid snakes with purified Torpedo californica nicotinic acetylcholine receptor (nAChR). The potency of an antivenom is determined by its antibody ability to bind and neutralize the PSNT, thus preventing it from binding to nAChR. The PSNT of Naja kaouthia (NK3) was immobilized on microtiter wells and nAChR was added to bind with it. The in vitro IC50 of N. kaouthia venom that inhibited 50% of nAChR binding to the immobilized NK3 was determined. Varying concentrations of antisera against N. kaouthia were separately pre-incubated with 5xIC50 of N. kaouthia venom. The remaining free NK3 were incubated with nAChR before adding to the NK3 coated plates. The in vitro and in vivo median effective ratio, ER50s of 12 batches of antisera showed correlation (R 2) of 0.9809 (p 
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