Displaying publications 41 - 60 of 71 in total

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  1. Preparation of antibodies to king cobra (Ophiophagus hannah) venom hemorrhagin and investigation of their cross-reactivity
    Tan NH, Saifuddin MN, Jaafar MI
    Toxicon, 1990;28(11):1355-9.
    PMID: 2128424
    Hannahtoxin, the major hemorrhagin purified from king cobra (Ophiophagus hannah) venom, elicits hemorrhages in rabbits but not in mice. Two antisera against hannahtoxin were prepared: one raised against purified hannahtoxin, while the other was raised against glutaraldehyde cross-linked and detoxified hannahtoxin. The antisera were refined by pepsin digestion and ammonium sulfate precipitation. They are of approximately equal potency in their ability to neutralize the hemorrhagic activity of king cobra venom in rabbits. The antisera did not form a precipitin line with venom of snakes of the Viperidae family nor neutralize hemorrhages elicited in mice by any of these venoms. However, when the hemorrhagic activity was assayed in rabbits, both antisera were able to abolish the hemorrhages elicited by all of the venoms tested. These results suggest that hannahtoxin displays few epitopes in common with hemorrhagins of viperid venoms, except those involved in the neutralization of hemorrhagic activity in rabbits. The epitopes of viperid venom hemorrhagins involved in the neutralization reaction in rabbits are different from those in mice.
  2. The lethal and biochemical properties of Bungarus candidus (Malayan krait) venom and venom fractions
    Tan NH, Poh CH, Tan CS
    Toxicon, 1989;27(9):1065-70.
    PMID: 2799837
    Bungarus candidus venom exhibited high hyaluronidase, acetylcholinesterase and phospholipase A activities; low proteinase, 5'-nucleotidase, alkaline phosphomonoesterase and phosphodiesterase activities and moderately high L-amino acid oxidase activity. SP-Sephadex C-50 ion exchange chromatographic fractionation of the venom and Sephadex G-50 chromatography of the major lethal venom fractions indicate that the venom contains at least two highly lethal, basic phospholipases A with LD50 (i.v.) values of 0.02 micrograms/g (F6A) and 0.18 micrograms/g (F4A), respectively; as well as two polypeptide toxins with LD50 (i.v.) values of 0.17 micrograms/g and 0.83 micrograms/g, respectively. The major lethal toxin is the basic lethal phospholipase A, F6A, which accounts for approximately 13% of the venom protein and has a mol. wt of 21,000.
  3. The use of enzyme-linked immunosorbent assay for the quantitation of Calloselasma rhodostoma (Malayan pit viper) venom and venom antibodies
    Tan NH, Yeo KH, Jaafar MI
    Toxicon, 1992 Dec;30(12):1609-20.
    PMID: 1488770
    The specificity and sensitivity of an indirect and two (an 'ordinary' and a 'rapid') double sandwich enzyme-linked immunosorbent assay (ELISA) procedures for the quantitation of Calloselasma rhodostoma (Malayan pit viper) venom were examined. The three assays were equally sensitive and the accuracy of the assays was not substantially affected by individual variation in the venom composition. The specificity of the assays was examined against 26 venoms from snakes of the families Viperidae and Elapidae. While the double sandwich ELISA procedures were sufficiently specific to be used in the clinical immunodiagnosis of C. rhodostoma bite in Malaysia, the indirect ELISA procedure exhibited extensive cross-reactivity with other Malaysian pit viper venoms. Attempts were made to improve the specificity of the indirect ELISA procedure for the quantitation of C. rhodostoma venom. A 'low ELISA cross-reactivity' venom fraction (termed VF52) was isolated from C. rhodostoma venom by repeated Sephadex G-100 gel filtration chromatography. The indirect ELISA procedure using antibodies to VF52 as immunoreagent showed an improvement in specificity. The use of the indirect ELISA procedure for the detection of C. rhodostoma antibodies was also examined and the results show that the assay was sufficiently specific to be used for retrospective diagnosis of C. rhodostoma bite in Malaysia, in particular when VF52 was used as the coating antigen.
  4. Isolation and characterization of a hemorrhagin from the venom of Calloselasma rhodostoma (Malayan pit viper)
    Ponnudurai G, Chung MC, Tan NH
    Toxicon, 1993 Aug;31(8):997-1005.
    PMID: 8212052
    The major hemorrhagin (termed rhodostoxin) of the venom of Calloselasma rhodostoma (Malayan pit viper) was purified to electrophoretic homogeneity by Sephadex G-200 gel filtration followed by high performance ion exchange chromatography. The purified hemorrhagin also yielded a single peak in reversed-phase HPLC. It had an isoelectric point of 5.3 and a mol. wt of 34,000. Rhodostoxin exhibited potent proteolytic, hemorrhagic and edema-inducing activities but was not lethal to mice at a dose of 6 microgram/g (i.v.). Treatment of rhodostoxin with EDTA eliminated both the proteolytic and hemorrhagic activities completely. The N-terminal sequence of rhodostoxin was determined to be NHEIKRHVDIVVVXDSRFCTK.
  5. An investigation into the antigenic cross-reactivity of Ophiophagus hannah (king cobra) venom neurotoxin, phospholipase A2, hemorrhagin and L-amino acid oxidase using enzyme-linked immunosorbent assay
    Tan NH, Lim KK, Jaafar MI
    Toxicon, 1993 Jul;31(7):865-72.
    PMID: 8212031
    The antigenic cross-reactivity of four Ophiophagus hannah (king cobra) venom components, the neurotoxin (OH-NTX), phospholipase A2 (OH-PLA2), hemorrhagin (OH-HMG) and L-amino acid oxidase (OH-LAAO) were examined by indirect and double sandwich ELISAs. The indirect ELISAs for OH-NTX, OH-PLA2 and OH-HMG were very specific when assayed against the various heterologous snake venoms and O. hannah venom components, at 25 ng/ml antigen level. At higher antigen concentrations (100-400 ng/ml), there were moderate to strong indirect ELISA cross-reactions between anti-O. hannah neurotoxin and venoms from various species of cobra as well as two short neurotoxins. However, anti-O. hannah hemorrhagin did not cross-react with any of the venoms tested, even at these high antigen concentrations, indicating that O. hannah hemorrhagin is antigenically very different from other venom hemorrhagins. Examination of the indirect ELISA cross-reactions between anti-O. hannah PLA2 and several elapid PLA2 enzymes suggests that the elapid PLA2 antigenic class has more than two subgroups. The antibodies to O. hannah L-amino acid oxidase, however, yielded indirect ELISA cross-reactions with many venoms as well as with OH-NTX, OH-PLA2 and OH-HMG, indicating that OH-LAAO shares common epitopes even with unrelated proteins. The double sandwich ELISAs for the four anti-O. hannah venom components, on the other hand, generally exhibited a higher degree of selectivity than the indirect ELISA procedure.
  6. A comparative study of the biological properties of venoms from juvenile and adult inland taipan (Oxyuranus microlepidotus) snake venoms
    Tan NH, Ponnudurai G, Mirtschin PJ
    Toxicon, 1993 Mar;31(3):363-7.
    PMID: 8470140
    The biological properties of adult and juvenile inland taipan (Oxyuranus microlepidotus) snake venoms were examined. The enzymatic activities, intravenous median lethal dose and procoagulant activity of the juvenile venom samples were not significantly different from those of the adult venom samples. Also, the juvenile and adult venoms exhibited similar electrophoretic patterns, indicating that they possessed similar protein composition.
  7. Proteolytic specificity of rhodostoxin, the major hemorrhagin of Calloselasma rhodostoma (Malayan pit viper) venom
    Tan NH, Ponnudurai G, Chung MC
    Toxicon, 1997 Jun;35(6):979-84.
    PMID: 9241791
    The proteolytic specificity of rhodostoxin, the major hemorrhagin from Calloselasma rhodostoma (Malayan pit viper) venom was investigated using oxidized B-chain of bovine insulin as substrate. Six peptide bonds were cleaved: Ser9-Hist10, His10-Leu11, Ala14-Leu15, Tyr16-Leu17, Gly20-Glu21 and Phe24-Phe25. Deglycosylated rhodostoxin, however, cleaved primarily at Arg22-Gly23.
  8. Fulltext Protective effects of Mucuna pruriens seed extract pretreatment against cardiovascular and respiratory depressant effects of Calloselasma rhodostoma (Malayan pit viper) venom in rats
    Fung SY, Tan NH, Sim SM
    Trop Biomed, 2010 Dec;27(3):366-72.
    PMID: 21399576 MyJurnal
    The protective effects of Mucuna pruriens seed extract (MPE) against the cardio-respiratory depressant and neuromuscular paralytic effects induced by injection of Calloselasma rhodostoma (Malayan pit viper) venom in anaesthetized rats were investigated. While MPE pretreatment did not reverse the inhibitory effect of the venom on the gastrocnemius muscle excitability, it significantly attenuated the venom-induced cardio-respiratory depressant effects (p < 0.05). The protection effects may have an immunological mechanism, as indicated by the presence of several proteins in the venom that are immunoreactive against anti-MPE. However, we cannot rule out the possibility that the pretreatment may exert a direct, non-immunological protective action against the venom.
  9. Inducing curricular change: Initial evaluation of outcomes
    Azila NM, Tan NH, Tan CP
    Med Educ, 2006 Nov;40(11):1125.
    PMID: 17054624
  10. The role of transvaginal sonography in the diagnosis of placenta praevia
    Tan NH, Abu M, Woo JL, Tahir HM
    Aust N Z J Obstet Gynaecol, 1995 Feb;35(1):42-5.
    PMID: 7771998 DOI: 10.1111/j.1479-828x.1995.tb01828.x
    Transvaginal sonography was performed in 70 patients diagnosed to have placenta praevia by transabdominal sonography. The diagnosis was confirmed either by digital examination in theatre at term or operative finding at delivery. Forty-nine cases (70%) were correctly diagnosed to have placenta praevia by both modes of sonography. Transvaginal sonography ruled out placenta praevia in 12 cases (17%) thought to be placenta praevia by transabdominal ultrasound. Both transabdominal and transvaginal sonography demonstrated 'placental migration' in 4 cases (6%) which were no longer praevia at delivery. Five patients (7%) were erroneously believed to have placenta praevia by both sonographic techniques. Overall, the diagnostic accuracy of transvaginal sonography was 92.8% compared with 75.7% for transabdominal sonography. None of the subjects experienced any exacerbation of bleeding or other complications. The results suggest that transvaginal sonographic localization of the placenta is safe and superior to the transabdominal route.
  11. Six isoforms of cardiotoxin in malayan spitting cobra (Naja naja sputatrix) venom: cloning and characterization of cDNAs
    Jeyaseelan K, Armugam A, Lachumanan R, Tan CH, Tan NH
    Biochim. Biophys. Acta, 1998 Apr 10;1380(2):209-22.
    PMID: 9565688
    Cardiotoxins are the most abundant toxin components of cobra venom. Although many cardiotoxins have been purified and characterized by amino acid sequencing and other pharmacological and biochemical studies, to date only five cardiotoxin cDNAs from Taiwan cobra (Naja naja atra), three cDNAs from Chinese cobra (Naja atra) and two more of uncertain origin (either Chinese or Taiwan cobra) have been reported. In this paper we show the existence of four isoforms of cardiotoxin by protein analysis and nine cDNA sequences encoding six isoforms of cardiotoxins (CTX 1-3, 4a, 4b and 5) from N. n. sputatrix by cDNA cloning. This forms the first report on the cloning and characterization of several cardiotoxin genes from a single species of a spitting cobra. The cDNAs encoding these isoforms, obtained by reverse transcription-polymerase chain reaction (RT-PCR), were subsequently expressed in Escherichia coli. The native and recombinant cardiotoxins were first characterized by Western blotting and N-terminal protein sequencing. These proteins were also found to have different levels of cytolytic activity on cultured baby hamster kidney cells. Four of the isoforms (CTX 1, 2, 4 and 5) are unique to N. n. sputatrix, with CTX 2 being the most abundant species constituting about 50% of the total cardiotoxins. The isoform CTX 3 (20% constitution) is highly homologous to the cardiotoxins of N. n. atra and N. n. naja, indicating that it may be universally present in all Naja naja subspecies. Our studies suggest that the most hydrophilic isoform (CTX 5) could have evolved first followed by the hydrophobic isoforms (CTX 1, 2, 3 and 4). We also speculate that Asiatic cobras could be the modern descendants of the African and Egyptian counterparts.
  12. Fulltext The role of general practitioners in the management of erectile dysfunction-a qualitative study
    Ng CJ, Low WY, Tan NC, Choo WY
    Int J Impot Res, 2004 Feb;16(1):60-3.
    PMID: 14963472 DOI: 10.1038/sj.ijir.3901141
    The objective of this study was to explore the roles and perceptions of general practitioners (GPs) in the management of erectile dysfunction (ED). This qualitative study used focus group discussions and in-depth interviews. This study was conducted based on 28 GPs from an urban area in Malaysia who had managed patients with ED and prescribed anti-ED drugs. Main outcome measures included the roles of GPs in managing patients with ED (active or passive), perceptions regarding ED and the treatment, and factors influencing their decision to prescribe. Majority of the GPs assumed a passive role when managing patients with ED. This was partly due to their perception of the disease being nonserious. Some also perceived ED as mainly psychological in nature. The anti-ED drugs were often viewed as a lifestyle drug with potentially serious side effects. The fear of being perceived by patients as 'pushing' for the drug and being blamed if the patients were to develop serious side effects also hampered the management of this disease. GPs who participated in this study remained passive in identifying and treating patients with ED and this was attributed to their perception of the disease, drug treatment and patient's background.
  13. Cross-reactivity of monovalent and polyvalent Trimeresurus antivenoms with venoms from various species of Trimeresurus (lance-headed pit viper) snake
    Tan NH, Choy SK, Chin KM, Ponnudurai G
    Toxicon, 1994 Jul;32(7):849-53.
    PMID: 7940592
    Trimeresurus bite is a serious medical problem in Asia. However, at present only a few monospecific Trimeresurus antivenoms are available. Investigation of the cross-neutralization capacity of three Trimeresurus antivenoms indicates that the antivenoms exhibit broad cross-reactivity. A polyvalent Trimeresurus antivenom was also found to be effective in neutralization of the haemorrhagic, necrotizing and thrombin-like activities of heterologous Trimeresurus venoms.
  14. Achieving triple treatment goals in multi-ethnic Asian patients with type 2 diabetes mellitus in primary care
    Goh CC, Koh KH, Goh S, Koh Y, Tan NC
    Malays Fam Physician, 2018;13(2):10-18.
    PMID: 30302178
    INTRODUCTION: Achieving optimal glycated hemoglobin (HbA1c), blood pressure (BP), and LDL-Cholesterol (LDL-C) in patients mitigates macro- and micro-vascular complications, which is the key treatment goal in managing type 2 diabetes mellitus (T2DM). This study aimed to determine the proportion of patients in an urban community with T2DM and the above modifiable conditions attaining triple vascular treatment goals based on current practice guidelines.

    METHODS: A questionnaire was distributed to adult Asian patients with dyslipidemia at two primary care clinics (polyclinics) in northeastern Singapore. The demographic and clinical data for this sub-population with both T2DM and dyslipidemia were collated with laboratory and treatment information retrieved from their electronic health records. The combined data was then analyzed to determine the proportion of patients who attained triple treatment goals, and logistic regression analysis was used to identify factors associated with this outcome.

    RESULTS: 665 eligible patients [60.5% female, 30.5% Chinese, 35% Malays, and 34.4% Indians] with a mean age of 60.6 years were recruited. Of these patients, 71% achieved LDL-C ≤2.6 mmol/L, 70.4% had BP

  15. Fulltext Antiproliferative activity of king cobra (Ophiophagus hannah) venom L-amino acid oxidase
    Li Lee M, Chung I, Yee Fung S, Kanthimathi MS, Hong Tan N
    Basic Clin Pharmacol Toxicol, 2014 Apr;114(4):336-43.
    PMID: 24118879 DOI: 10.1111/bcpt.12155
    King cobra (Ophiophagus hannah) venom L-amino acid oxidase (LAAO), a heat-stable enzyme, is an extremely potent antiproliferative agent against cancer cells when compared with LAAO isolated from other snake venoms. King cobra venom LAAO was shown to exhibit very strong antiproliferative activities against MCF-7 (human breast adenocarcinoma) and A549 (human lung adenocarcinoma) cells, with an IC50 value of 0.04±0.00 and 0.05±0.00 μg/mL, respectively, after 72-hr treatment. In comparison, its cytotoxicity was about 3-4 times lower when tested against human non-tumourigenic breast (184B5) and lung (NL 20) cells, suggesting selective antitumour activity. Furthermore, its potency in MCF-7 and A549 cell lines was greater than the effects of doxorubicin, a clinically established cancer chemotherapeutic agent, which showed an IC50 value of 0.18±0.03 and 0.63±0.21 μg/mL, respectively, against the two cell lines. The selective cytotoxic action of the LAAO was confirmed by phycoerythrin (PE) annexin V/7-amino-actinomycin (AAD) apoptotic assay, in which a significant increase in apoptotic cells was observed in LAAO-treated tumour cells than in their non-tumourigenic counterparts. The ability of LAAO to induce apoptosis in tumour cells was further demonstrated using caspase-3/7 and DNA fragmentation assays. We also determined that this enzyme may target oxidative stress in its killing of tumour cells, as its cytotoxicity was significantly reduced in the presence of catalase (a H2O2 scavenger). In view of its heat stability and selective and potent cytotoxic action on cancer cells, king cobra venom LAAO can be potentially developed for treating solid tumours.
  16. Nutrient composition, antioxidant properties, and anti-proliferative activity of Lignosus rhinocerus Cooke sclerotium
    Yap YH, Tan N, Fung S, Aziz AA, Tan C, Ng S
    J Sci Food Agric, 2013 Sep;93(12):2945-52.
    PMID: 23460242 DOI: 10.1002/jsfa.6121
    Lignosus rhinocerus (tiger milk mushroom) is an important medicinal mushroom used in Southeast Asia and China, and its sclerotium can be developed into functional food/nutraceuticals. The nutrient composition, antioxidant properties, and anti-proliferative activity of wild type and a cultivated strain of L. rhinocerus sclerotia were investigated.
  17. Dilemma in the management of methanol poisoning at a district hospital in Malaysia
    Low QJ, Lee KT, Lim TH, Siaw C, Cheo SW, Tan NE, et al.
    Med J Malaysia, 2020 07;75(4):442-444.
    PMID: 32724013
    There are increasing reports of methanol poisoning (MP) incidence worldwide. In Malaysia, the largest first methanol poisoning was reported in Selangor in 2013 with a total of 41 patients and cluster of cases been reported from the country since then. Often MP involved adulterated alcohol containing more than the legal permissible concentration of methanol. Methanol is rapidly absorbed and metabolised into formic acid which causes variable symptoms of the central nervous system such as blindness, seizure, coma and gastrointestinal disturbances. Mortality could reach up to 83% as reported using the coma state, pH and pCO2 level in the worst-case scenario.
  18. Regional and accelerated molecular evolution in group I snake venom gland phospholipase A2 isozymes
    Chuman Y, Nobuhisa I, Ogawa T, Deshimaru M, Chijiwa T, Tan NH, et al.
    Toxicon, 2000 Mar;38(3):449-62.
    PMID: 10669032
    In accordance with detection of a few phospholipase A2 (PLA2) isozyme genes by Southern blot analysis, only two cDNAs, named NnkPLA-I , and NnkPLA-II, encoding group I PLA2s, NnkPLA-I and NnkPLA-II, respectively, were isolated from the venom gland cDNA library of Elapinae Naja naja kaouthia of Malaysia. NnkPLA-I and NnkPLA-II showed four amino acid substitutions, all of which were brought about by single nucleotide substitution. No existence of clones encoding CM-II and CM-III, PLA2 isozymes which had been isolated from the venom of N. naja kaouthia of Thailand, in Malaysian N. naja kaouthia venom gland cDNA library was verified by dot blot hybridization analysis with particular probes. NnkPLA-I and NnkPLA-II differed from CM-II and CM-III with four and two amino acid substitutions, respectively, suggesting that their molecular evolution is regional. The comparison of NnkPLA-I, NnkPLA-II and cDNAs encoding other group I snake venom gland PLA2s indicated that the 5'- and 3'-untranslated regions are more conserved than the mature protein-coding region and that the number of nucleotide substitutions per nonsynonymous site is almost equal to that per synonymous site in the protein-coding region, suggesting that accelerated evolution has occurred in group I venom gland PLA2s possibly to acquire new physiological functions.
  19. Cloning and characterization of cDNAs encoding three isoforms of phospholipase A2 in Malayan spitting cobra (Naja naja sputatrix) venom
    Armugam A, Earnest L, Chung MC, Gopalakrishnakone P, Tan CH, Tan NH, et al.
    Toxicon, 1997 Jan;35(1):27-37.
    PMID: 9028006
    cDNAs encoding three phospholipase A2 (PLA2) isoforms in Naja naja sputatrix were cloned and characterized. One of them encoded an acidic PLA2 (APLA) while the others encoded neutral PLA2 (NPLA-1 and NPLA-2). The specific characteristics of APLA and NPLA were attributed to mutations at nt139 and nt328 from G to C and G to A, respectively, resulting in amino acid substitutions from Asp20 and 83 in APLA to His20 and Asn83 in NPLA. Amino acid sequencing of purified protein also showed the presence of this Asp20 and His20 in APLA and NPLA, respectively. The cDNA encoding one of the PLA2 (NAJPLA-2A), when expressed in Escherichia coli, yielded a protein that exhibited PLA2 activity.
  20. Electrophoretic profiles and biological activities: intraspecific variation in the venom of the Malayan pit viper (Calloselasma rhodostoma)
    Daltry JC, Ponnudurai G, Shin CK, Tan NH, Thorpe RS, Wüster W
    Toxicon, 1996 Jan;34(1):67-79.
    PMID: 8835335
    The Malayan pit viper (Calloselasma rhodostoma) is of major clinical significance both as a leading cause of snakebite and as the source of ancrod (Arvin). Although its venom has been extensively studied, the degree to which venom composition varies between individuals is poorly known. We individually analysed the venoms of over 100 C. rhodostoma using isoelectric focusing. In all populations, females produced an intense band that was absent from all males, and significant ontogenetic variation was detected. Principal components analysis of the banding profiles also revealed strong geographic variation, which was significantly congruent with variation in the biological activities of the venom (phosphodiesterase, alkalinephosphoesterase, L-amino acid oxidase, arginine ester hydrolase, 5'-nucleotidase, thrombin-like enzyme, haemorrhagic activity). Studies of captive-bred snakes indicate that the intraspecific variation in venom is genetically inherited rather than environmentally induced. The intraspecific variation in venom composition and biological activity could be of applied importance to snakebite therapy, both in correct diagnosis of the source of envenomation and in the development of a more effective antivenom. Greater attention should be given to the source of C. rhodostoma venom used in research to ensure reproducibility of results.
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