Displaying publications 1 - 20 of 197 in total

Abstract:
Sort:
  1. Cheong, C.Y., Lee, C.K., Zuki Z.
    Malays Orthop J, 2010;4(1):-.
    MyJurnal
    Snakebite is very common especially in Asia. We report a rare case of Providencia rettgeri infection following snakebite on the foot. This patient was treated with early and aggressive wound debridement, daily wound dressing during hospitalization and then skin coverage with split skin graft. No anti-venom was given administered. Appropriate intravenous antibiotics were given to the patient while hospitalized and oral antibiotic were prescribed upon discharge. The outcome of this treatment was successful.
    Matched MeSH terms: Venoms
  2. Rothan HA, Bahrani H, Shankar EM, Rahman NA, Yusof R
    Antiviral Res, 2014 Aug;108:173-80.
    PMID: 24929084 DOI: 10.1016/j.antiviral.2014.05.019
    Chikungunya virus (CHIKV) outbreaks have led to a serious economic burden, as the available treatment strategies can only alleviate disease symptoms, and no effective therapeutics or vaccines are currently available for human use. Here, we report the use of a new cost-effective approach involving production of a recombinant antiviral peptide-fusion protein that is scalable for the treatment of CHIKV infection. A peptide-fusion recombinant protein LATA-PAP1-THAN that was generated by joining Latarcin (LATA) peptide with the N-terminus of the PAP1 antiviral protein, and the Thanatin (THAN) peptide to the C-terminus, was produced in Escherichia coli as inclusion bodies. The antiviral LATA-PAP1-THAN protein showed 89.0% reduction of viral plaque formation compared with PAP1 (46.0%), LATA (67.0%) or THAN (79.3%) peptides alone. The LATA-PAP1-THAN protein reduced the viral RNA load that was 0.89-fold compared with the untreated control cells. We also showed that PAP1 resulted in 0.44-fold reduction, and THAN and LATA resulting in 0.78-fold and 0.73-fold reductions, respectively. The LATA-PAP1-THAN protein inhibited CHIKV replication in the Vero cells at an EC50 of 11.2μg/ml, which is approximately half of the EC50 of PAP1 (23.7μg/ml) and protected the CHIKV-infected mice at the dose of 0.75mg/ml. We concluded that production of antiviral peptide-fusion protein in E. coli as inclusion bodies could accentuate antiviral activities, enhance cellular internalisation, and could reduce product toxicity to host cells and is scalable to epidemic response quantities.
    Matched MeSH terms: Spider Venoms/genetics; Spider Venoms/pharmacology; Spider Venoms/therapeutic use*
  3. Tan NH, Saifuddin MN, Yong WY
    Biochem. Int., 1991 Jan;23(1):175-81.
    PMID: 1863271
    The edema inducing activity of phospholipase A2 (PLA2) enzymes from snake venoms and porcine pancreas was investigated using mouse paw as experimental model. All ten PLA2 enzymes exhibited potent edema inducing activity. PLA2, however, is generally not the major edema inducing component of snake venom. Chemical modification studies indicated that enzymatic activity of PLA2 was required for its edema inducing activity. All PLA2 enzymes examined displayed a rapid onset edema which was suppressed by pretreatment of the mice with antihistamine. Dexamethasone pretreatment also inhibited edemas elicited by some PLA2 enzymes.
    Matched MeSH terms: Snake Venoms/toxicity
  4. Tan NH, Fung SY, Yap YH
    PMID: 21983189 DOI: 10.1016/j.cbpb.2011.09.009
    A thrombin-like enzyme (termed albolabrase) was isolated in purified form from the venom of Cryptelytrops albolabris (white-lipped tree viper) using high performance anion ion exchange and gel filtration chromatography. The molecular mass of albolabrase was 33.7 kDa as determined by SDS-PAGE and 35.8 kDa as determined by Superose gel filtration chromatography. The N-terminal sequence was determined to be VVGGDECNINE which is homologous to many snake venom thrombin-like enzymes. Albolabrase exhibits both arginine ester hydrolase and arginine amidase activities and the enzyme is fastidious towards tripeptide chromogenic anilide substrates. The fibrinogen clotting activity was optimum at 3mg/mL bovine fibrinogen, and showed distinct species differences in the following decreasing order: bovine fibrinogen>dog fibrinogen≈human fibrinogen>goat fibrinogen. The enzyme failed to clot both rabbit and cat fibrinogens. Reversed-phase HPLC analysis on the breakdown products of fibrinogenolytic action of albolabrase indicated that the enzyme belongs to the AB class of snake venom thrombin-like enzyme. In the indirect ELISA, IgG anti-albolabrase reacted extensively with most crotalid venoms, except with Tropidolaemus wagleri and Calloselasma rhodostoma venoms. The double sandwich ELISA, however, showed that anti-albolabrase reacted strongly only with venoms from the Trimeresurus complex, and that the results support the proposed new taxonomy changes concerning the Trimeresurus complex.
    Matched MeSH terms: Viper Venoms/enzymology*
  5. Hiu JJ, Yap MKK
    Int J Biol Macromol, 2021 Aug 01;184:776-786.
    PMID: 34174307 DOI: 10.1016/j.ijbiomac.2021.06.145
    Naja sumatrana venom cytotoxin (sumaCTX) is a basic protein which belongs to three-finger toxin family. It has been shown to induce caspase-dependent, mitochondrial-mediated apoptosis in MCF-7 cells at lower concentrations. This study aimed to investigate the alteration of secretome in MCF-7 cells following membrane permeabilization by high concentrations of sumaCTX, using label-free quantitative (LFQ) approach. The degree of membrane permeabilization of sumaCTX was determined by lactate dehydrogenase (LDH) assay and calcein-propidium iodide (PI) assays. LDH and calcein-PI assays revealed time-dependent membrane permeabilization within a narrow concentration range. However, as toxin concentrations increased, prolonged exposure of MCF-7 cells to sumaCTX did not promote the progression of membrane permeabilization. The secretome analyses showed that membrane permeabilization was an event preceding the release of intracellular proteins. Bioinformatics analyses of the LFQ secretome revealed the presence of 105 significantly distinguished proteins involved in metabolism, structural supports, inflammatory responses, and necroptosis in MCF-7 cells treated with 29.8 μg/mL of sumaCTX. Necroptosis was presumably an initial stress response in MCF-7 cells when exposed to high sumaCTX concentration. Collectively, sumaCTX-induced the loss of membrane integrity in a concentration-dependent manner, whereby the cell death pattern of MCF-7 cells transformed from apoptosis to necroptosis with increasing toxin concentrations.
    Matched MeSH terms: Elapid Venoms/pharmacology
  6. Hiu JJ, Yap MKK
    Biochem Soc Trans, 2020 04 29;48(2):719-731.
    PMID: 32267491 DOI: 10.1042/BST20200110
    The phospholipase A2 (PLA2) and l-amino acid oxidase (LAAO) are two major enzymes found in the venoms from most snake species. These enzymes have been structurally and functionally characterised for their pharmacological activities. Both PLA2 and LAAO from different venoms demonstrate considerable cytotoxic effects on cancer cells via induction of apoptosis, cell cycle arrest and suppression of proliferation. These enzymes produce more pronounced cytotoxic effects in cancer cells than normal cells, thus they can be potential sources as chemotherapeutic agents. It is proposed that PLA2 and LAAO contribute to an elevated oxidative stress due to their catalytic actions, for instance, the ability of PLA2 to produce reactive oxygen species during lipolysis and formation of H2O2 from LAAO catalytic activity which consequently lead to cell death. Nonetheless, the cell-death signalling pathways associated with exposure to these enzymatic toxins are not fully elucidated yet. Here in this review, we will discuss the cytotoxic effects of PLA2 and LAAO in relationship to their catalytic mechanisms and the underlying mechanisms of cytotoxic actions.
    Matched MeSH terms: Venoms
  7. Yong Y, Hiu JJ, Yap MKK
    Adv Protein Chem Struct Biol, 2023;133:193-230.
    PMID: 36707202 DOI: 10.1016/bs.apcsb.2022.08.001
    Snake envenomation is listed as Category A Neglected Tropical Diseases (NTD) by World Health Organization, indicates a severe public health problem. The global figures for envenomation cases are estimated to be more than 1.8 million annually. Even if the affected victims survive the envenomation, they might suffer from permanent morbidity due to local envenomation. One of the most prominent local envenomation is dermonecrosis. Dermonecrosis is a pathophysiological outcome of envenomation that often causes disability in the victims due to surgical amputations, deformities, contracture, and chronic ulceration. The key venom toxins associated with this local symptom are mainly attributed to substantial levels of enzymatic and non-enzymatic toxins as well as their possible synergistic actions. Despite so, the severity of the local tissue damage is based on macroscopic observation of the bite areas. Furthermore, limited knowledge is known about the key biomarkers involved in the pathogenesis of dermonecrosis. The current immunotherapy with antivenom is also ineffective against dermonecrosis. These local effects eventually end up as sequelae. There is also a global shortage of toxins-targeted therapeutics attributed to inadequate knowledge of the actual molecular mechanisms of cytotoxicity. This chapter discusses the characterization of secretory phenotypes of dermonecrosis as an advanced tool to indicate its severity and pathogenesis in envenomation. Altogether, the secretory phenotypes of envenomed cells and tissues represent the precise characteristics of dermonecrosis caused by venom toxins.
    Matched MeSH terms: Venoms*
  8. Hiu JJ, Fung JKY, Tan HS, Yap MKK
    Sci Rep, 2023 Jul 28;13(1):12271.
    PMID: 37507457 DOI: 10.1038/s41598-023-39222-2
    Approximate 70% of cobra venom is composed of cytotoxin (CTX), which is responsible for the dermonecrotic symptoms of cobra envenomation. However, CTX is generally low in immunogenicity, and the antivenom is ineffective in attenuating its in vivo toxicity. Furthermore, little is known about its epitope properties for empirical antivenom therapy. This study aimed to determine the epitope sequences of CTX using the immunoinformatic analyses and epitope-omics profiling. A conserved CTX was used in this study to determine its T-cell and B-cell epitope sequences using immunoinformatic tools and molecular docking simulation with different Human Leukocyte Antigens (HLAs). The potential T-cell and B-cell epitopes were 'KLVPLFY,' 'CPAGKNLCY,' 'MFMVSTPTK,' and 'DVCPKNSLL.' Molecular docking simulations disclosed that the HLA-B62 supertype exhibited the greatest binding affinity towards cobra venom cytotoxin. The namely L7, G18, K19, N20, M25, K33, V43, C44, K46, N47, and S48 of CTX exhibited prominent intermolecular interactions with HLA-B62. The multi-enzymatic-limited-digestion/liquid chromatography-mass spectrometry (MELD/LC-MS) also revealed three potential epitope sequences as 'LVPLFYK,' 'MFMVS,' and 'TVPVKR'. From different epitope mapping approaches, we concluded four potential epitope sites of CTX as 'KLVPLFYK', 'AGKNL', 'MFMVSTPKVPV' and 'DVCPKNSLL'. Site-directed mutagenesis of these epitopes confirmed their locations at the functional loops of CTX. These epitope sequences are crucial to CTX's structural folding and cytotoxicity. The results concluded the epitopes that resided within the functional loops constituted potential targets to fabricate synthetic epitopes for CTX-targeted antivenom production.
    Matched MeSH terms: Elapid Venoms*
  9. 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.
    Matched MeSH terms: Viper Venoms/enzymology*; Viper Venoms/metabolism; Viper Venoms/toxicity
  10. Tan CH, Wong KY, Huang LK, Tan KY, Tan NH, Wu WG
    Toxins (Basel), 2022 Dec 07;14(12).
    PMID: 36548757 DOI: 10.3390/toxins14120860
    Naja nivea (Cape Cobra) is endemic to southern Africa. Envenoming by N. nivea is neurotoxic, resulting in fatal paralysis. Its venom composition, however, has not been studied in depth, and specific antivenoms against it remain limited in supply. Applying a protein decomplexation approach, this study unveiled the venom proteome of N. nivea from South Africa. The major components in the venom are cytotoxins/cardiotoxins (~75.6% of total venom proteins) and alpha-neurotoxins (~7.4%), which belong to the three-finger toxin family. Intriguingly, phospholipase A2 (PLA2) was undetected-this is a unique venom phenotype increasingly recognized in the African cobras of the Uraeus subgenus. The work further showed that VINS African Polyvalent Antivenom (VAPAV) exhibited cross-reactivity toward the venom and immunorecognized its toxin fractions. In mice, VAPAV was moderately efficacious in cross-neutralizing the venom lethality with a potency of 0.51 mg/mL (amount of venom completely neutralized per milliliter of antivenom). In the challenge-rescue model, VAPAV prevented death in 75% of experimentally envenomed mice, with slow recovery from neurotoxicity up to 24 h. The finding suggests the potential para-specific utility of VAPAV for N. nivea envenoming, although a higher dose or repeated administration of the antivenom may be required to fully reverse the neurotoxic effect of the venom.
    Matched MeSH terms: Elapid Venoms/metabolism; Elapid Venoms/toxicity
  11. Ismail AK, Weinstein SA, Auliya M, Sabardin DM, Herbosa TJ, Saiboon IM, et al.
    Clin Toxicol (Phila), 2010 Mar;48(3):222-6.
    PMID: 20345298 DOI: 10.3109/15563650903550964
    The Twin-Barred Tree Snake, Chrysopelea pelias, is a colubrine that, like other members of the genus Chrysopelea, is able to glide in the arboreal strata. Little is known about the effects of its bite. This report is the first clinically documented bite by this relatively uncommon rear-fanged species.
    Matched MeSH terms: Snake Venoms/toxicity*
  12. Tay TK, Chan HZ, Ahmad TS, Teh KK, Low TH, Wahab NA
    J Occup Med Toxicol, 2016;11:23.
    PMID: 27168760 DOI: 10.1186/s12995-016-0112-y
    BACKGROUND: Marine stings and envenomation are fairly common in Malaysia. Possible contact to various marine life occurs during diving, fishing and food handling. Even though majority of fish stings are benign, there are several venomous species such as puffer fish, scorpion fish, lionfish, stingray and stonefish that require urgent medical treatment. Stonefish is one of the most venomous fish in the world with potential fatal local and systemic toxicity effects to human.

    CASE PRESENTATION: We reported a case of stonefish sting complicated with impending compartment syndrome.

    CONCLUSIONS: Medical staff should be alert about the possibility of this potential emergency in standard management of stonefish stings.

    Matched MeSH terms: Fish Venoms; Venoms
  13. Vinazzer H
    Wien Z Inn Med, 1971;52(8):378-92.
    PMID: 5110844
    Matched MeSH terms: Venoms/therapeutic use*
  14. Vinazzer H
    Subsid Med, 1974;4:53-5.
    PMID: 4450561
    Matched MeSH terms: Venoms
  15. Ambikabothy J, Ibrahim H, Ambu S, Chakravarthi S, Awang K, Vejayan J
    J Ethnopharmacol, 2011 Sep 1;137(1):257-62.
    PMID: 21640180 DOI: 10.1016/j.jep.2011.05.013
    Evaluations of the anti-snake venom efficacy of Mimosa pudica tannin isolate (MPT) obtained from root of the plant.
    Matched MeSH terms: Cobra Venoms/enzymology; Cobra Venoms/toxicity*
  16. Williams HF, Mellows BA, Mitchell R, Sfyri P, Layfield HJ, Salamah M, et al.
    PLoS Negl Trop Dis, 2019 01;13(1):e0007041.
    PMID: 30695027 DOI: 10.1371/journal.pntd.0007041
    Snakebite is a major neglected tropical health issue that affects over 5 million people worldwide resulting in around 1.8 million envenomations and 100,000 deaths each year. Snakebite envenomation also causes innumerable morbidities, specifically loss of limbs as a result of excessive tissue/muscle damage. Snake venom metalloproteases (SVMPs) are a predominant component of viper venoms, and are involved in the degradation of basement membrane proteins (particularly collagen) surrounding the tissues around the bite site. Although their collagenolytic properties have been established, the molecular mechanisms through which SVMPs induce permanent muscle damage are poorly understood. Here, we demonstrate the purification and characterisation of an SVMP from a viper (Crotalus atrox) venom. Mass spectrometry analysis confirmed that this protein is most likely to be a group III metalloprotease (showing high similarity to VAP2A) and has been referred to as CAMP (Crotalus atrox metalloprotease). CAMP displays both collagenolytic and fibrinogenolytic activities and inhibits CRP-XL-induced platelet aggregation. To determine its effects on muscle damage, CAMP was administered into the tibialis anterior muscle of mice and its actions were compared with cardiotoxin I (a three-finger toxin) from an elapid snake (Naja pallida) venom. Extensive immunohistochemistry analyses revealed that CAMP significantly damages skeletal muscles by attacking the collagen scaffold and other important basement membrane proteins, and prevents their regeneration through disrupting the functions of satellite cells. In contrast, cardiotoxin I destroys skeletal muscle by damaging the plasma membrane, but does not impact regeneration due to its inability to affect the extracellular matrix. Overall, this study provides novel insights into the mechanisms through which SVMPs induce permanent muscle damage.
    Matched MeSH terms: Viper Venoms
  17. Mariam K, Tu AT
    J Nat Toxins, 2002 Dec;11(4):393-8.
    PMID: 12503884
    Sea snake venoms contain less protein than those of land snakes (Toom et al., 1969). Sea snake venoms lack arginine ester hydrolyzing activity, whereas those of Crotalidae and Viperidae have such activity (Tu et al., 1966). Sea snakes live in salty water, and their venoms may be different from those of land snakes. Because of the difficulty in obtaining sea snake venoms, information about sea snake venoms is quite incomplete. NGF is commonly present in the venoms of land snakes such as Elapidae, Viperidae, and Crotalidae (Cohen and Levi-Montalcini, 1956; Lipps, 2002). It is therefore of interest to investigate the presence or absence of NGF in sea snake venoms. In order to investigate the presence or absence of NGF, five sea snake venoms were selected. Lapemis hardwickii (Hardwick's sea snake) and Acalyptophis peronii venom were obtained from the Gulf of Thailand. Hydrophis cyanocinctus (common sea snake) and Enhydrina schistosa (beaked sea snake) venom were obtained from the Strait of Malacca. Laticauda semifasciata (broad band blue sea snake) venom was also examined and the venom was obtained from Gato Island in the Philippines.
    Matched MeSH terms: Cobra Venoms/biosynthesis; Elapid Venoms/metabolism*
  18. Trishnananda M
    PMID: 524149
    There are regional patterns in snake-bites. Bites by cobras have a high incidence in Thailand and in the Philippines with a high case fatality rate. Among the venomous snakes of haemorrhagic nature, bites by Trimeresurus species such as green pit viper, Taiwan habu and Taiwan bamboo viper are important in Thailand and Taiwan for their high incidence of bite, although the case fatality rates are low. Bites by Malayan pit vipers are also important in Thailand and Malaysia because of their high incidence. Bites by sea snakes are more common in Malaysia than in the Philippines and Thailand.
    Matched MeSH terms: Snake Venoms
  19. 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.

    Matched MeSH terms: Elapid Venoms/chemistry*
  20. 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.
    Matched MeSH terms: Cobra Venoms/poisoning*; Cobra Venoms/chemistry*
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links