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Cross neutralization of Hypnale hypnale (hump-nosed pit viper) venom by polyvalent and monovalent Malayan pit viper antivenoms in vitro and in a rodent model

Tan CH, Leong PK, Fung SY, Sim SM, Ponnudurai G, Ariaratnam C, et al.

Acta Trop, 2011 Feb;117(2):119-24.
PMID: 21073851 DOI: 10.1016/j.actatropica.2010.11.001

Hypnale hypnale (hump-nosed pit viper) is a medically important venomous snake in Sri Lanka and Southwestern India. Bite of this snake may result in hemostatic dysfunction, acute kidney injury and death. Clinical studies indicated that the locally available polyvalent antivenoms produced in India are not effective against hump-nosed pit viper envenoming. Hence, there is an urgent need to search for effective antivenom. In this paper, we examined the ability of Calloselasma rhodostoma (Malayan pit viper) monovalent antivenom and the Hemato polyvalent antivenom (both produced by Thai Red Cross Society, TRCS) to neutralize the lethality and toxic effects of H. hypnale venom, as C. rhodostoma is considered a sister taxon of H. hypnale. In vitro neutralization studies showed that the Hemato polyvalent antivenom effectively neutralized the lethality of H. hypnale venom (1.52mgvenom/mL antivenom) as well as the hemorrhagic, procoagulant and necrotic activities of the venom. The monovalent C. rhodostoma antivenom could also neutralize the lethality and toxic activities of the venom, but the potency was lower. The Hemato polyvalent antivenom also effectively protected mice from the lethal and local effects of H. hypnale venom in an in vivo rodent model of envenoming. Furthermore, the polyvalent antivenom could also effectively neutralize the venom of Daboia russelii (2.50mgvenom/mL antivenom), another common cause of snake bites in Sri Lanka and South India. These findings suggested that the Hemato polyvalent antivenom may be beneficial in the antivenom treatment of H. hypnale envenoming.
Purification and properties of the L-amino acid oxidase from Malayan pit viper (Calloselasma rhodostoma) venom

Ponnudurai G, Chung MC, Tan NH

Arch Biochem Biophys, 1994 Sep;313(2):373-8.
PMID: 8080286

The L-amino acid oxidase of Malayan pit viper (Calloselasma rhodostoma) venom was purified to electrophoretic homogeneity. The molecular weight of the enzyme was 132,000 as determined by Sephadex G-200 gel filtration chromatography and 66,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It is a glycoprotein, has an isoelectric point of 4.4, and contains 2 mol of flavin mononucleotide per mole of enzyme. The N-terminal amino acid sequence of the enzyme was A-D-D-R-N-P-L-A-E-E-F-Q-E-N-N-Y-E-E-F-L. Kinetic studies suggest the presence of a alkyl side-chain binding site in the enzyme and that the binding site comprises at least four hydrophobic subsites. The characteristics of the binding site differ slightly from those of cobra venom L-amino acid oxidases.
Fulltext A study of the nature and level of trust between patients and healthcare providers, its dimensions and determinants: a scoping review protocol

Rasiah S, Jaafar S, Yusof S, Ponnudurai G, Chung KPY, Amirthalingam SD

BMJ Open, 2020 Jan 23;10(1):e028061.
PMID: 31980505 DOI: 10.1136/bmjopen-2018-028061

INTRODUCTION: The aim of this scoping review is to systematically search the literature to identify the nature and or level of trust between the patient, the users of health services (eg, clients seeking health promotion and preventive healthcare services) and the individual healthcare providers (doctors, nurses and physiotherapists/ occupational therapists), across public and private healthcare sectors, at all levels of care from primary through secondary to tertiary care. It also aims to identify the factors that influence trust between patients, users of health services (clients) and providers of healthcare at all levels of care from primary care to tertiary care, and across all health sectors (public and private). The study will also identify the tools used to measure trust in the healthcare provider.
METHODS AND ANALYSIS: The scoping review will be conducted based on the methodology developed by Arksey and O'Malley's scoping review methodology, and Levac et al 's methodological enhancement. An experienced information specialist (HM) searched the following databases MEDLINE, EMBASE, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature. The search terms were both keywords in the title and/or abstract and subject headings (eg, MeSH, EMTREE) as appropriate. Search results were downloaded, imported and stored into a 'Refworks' folder specifically created for reference management. The preliminary search was conducted between 7 December 2017 and 14 December 2017. Quantitative methods using content analysis will be used to categorise study findings on factors associated with trust between patients, clients and healthcare providers. The collection of studies will be also examined for heterogeneity. Qualitative analysis on peer reviewed articles of qualitative interviews and focus group discussion will be conducted; it allows clear identification of themes arising from the data, facilitating prioritisation, higher order abstraction and theory development. A consultation exercise with stakeholders may be incorporated as a knowledge translation component of the scoping study methodology.
ETHICS AND DISSEMINATION: Ethical approval will be obtained for the research project from the Institutional Review Board. The International Medical University will use the findings of this scoping review research to improve the understanding of trust in healthcare, in its endeavour to improve health services delivery in its healthcare clinics and hospitals, and in its teaching and learning curriculum. The findings will also help faculty make evidence based decisions to focus resources and research as well as help to advance the science in this area. Dissemination of the results of the scoping review will be made through peer-reviewed publications, research reports and presentations at conferences and seminars.
A comparative study on the biological properties of venoms from juvenile and adult common tiger snake (Notechis scutatus) venoms

Tan NH, Ponnudurai G, Mirtschin PJ

Comp. Biochem. Physiol., B, 1993 Nov;106(3):651-4.
PMID: 8281760

1. The biological properties of venoms from juvenile and adult common tiger snakes (Notechis scutatus) were compared. 2. The lethality, procoagulant activity and enzymatic activities of the juvenile venom were not substantially different from those of the adult venom. 3. Electrophoretic studies, however, indicated some minor differences in the protein composition of the juvenile and adult venoms.
The biological properties of venoms of some American coral snakes (Genus micrurus)

Tan NH, Ponnudurai G

Comp. Biochem. Physiol., B, 1992 Mar;101(3):471-4.
PMID: 1582185

1. The biological properties of nine venom samples from six taxa of Micrurus were investigated. The venoms exhibited low protease, phosphodiesterase and 5'-nucleotidase activities, moderate to strong phospholipase A and hyaluronidase activities, variable L-amino acid oxidase activity and were devoid of arginine ester hydrolase and thrombin-like activities. Some venom samples exhibited strong acetylcholinesterase activity. Venoms of M. c. dumerili and M. frontalis exhibited exceptionally high alkaline phosphomonoesterase activity while two of the M. f. fulvius venom samples tested exhibited strong hemorrhagic activity in mice. 2. The polyacrylamide gel electrophoretic patterns of the venoms indicate that most of the Micrurus venom proteins are basic proteins. All Micrurus venoms tested exhibited similar SDS-polyacrylamide gel electrophoretic patterns, with an intense low mol. wt protein band. 3. The Micrurus venoms appear to exhibit biological properties similar to other elapid venoms found in Asia and Africa. There are, however, no common characteristics in the biological properties of the venoms examined at the generic level.
A comparative study on the electrophoretic patterns of snake venoms

Tan NH, Ponnudurai G

Comp. Biochem. Physiol., B, 1992 May;102(1):103-9.
PMID: 1526113

1. Examination of the polyacrylamide gel electrophoretic (PAGE) and SDS-PAGE patterns of snake venoms shows that these patterns are useful for species differentiation (and hence identification) for snakes of certain genera but have only limited application for snakes from some other genera, due either to the marked individual variations in the venoms or the lack of marked interspecific differences within the same genus. 2. There is no substantial intersubspecific difference in the electrophoretic patterns of the venoms. 3. In general there are no common characteristics in the electrophoretic patterns of the venom at the generic level because of the wide variations in the electrophoretic patterns of venoms of snakes within the same genus. 4. At the familial level, the venoms of Elapidae exhibited SDS-PAGE patterns distinct from those of Crotalidae.
A comparative study of the biological properties of some sea snake venoms

Tan NH, Ponnudurai G

Comp. Biochem. Physiol., B, 1991;99(2):351-4.
PMID: 1764914

1. The protease, phosphodiesterase, alkaline phosphomonoesterase, L-amino acid oxidase, acetylcholinesterase, phospholipase A, 5'-nucleotidase, hyaluronidase, arginine ester hydrolase, procoagulant, anticoagulant and hemorrhagic activities of ten samples of venoms from seven taxa of sea snakes were examined. 2. The results show that venoms of sea snakes of both subfamilies of Hydrophiinae and Laticaudinae are characterized by a very low level of enzymatic activities, except phospholipase A activity and, for some species, hyaluronidase activity. 3. Because of the low levels of enzymatic activities and the total lack of procoagulant and hemorrhagic activities, venom biological properties are not useful for the differentiation of species of sea snakes. Nevertheless, the unusually low levels of enzymatic activities of sea snake venoms may be used to distinguish sea snake venoms from other elapid or viperid venoms.
A comparative study of the biological properties of some venoms of snakes of the genus Bothrops (American lance-headed viper)

Tan NH, Ponnudurai G

Comp. Biochem. Physiol., B, 1991;100(2):361-5.
PMID: 1799979

1. The hemorrhagic, procoagulant, anticoagulant, phosphodiesterase, alkaline phosphomonoesterase, 5'-nucleotidase, hyaluronidase, arginine ester hydrolase, phospholipase A, L-amino acid oxidase and protease activities of 26 samples of venoms from 13 species of Bothrops were determined, and the Sephadex G-75 gel filtration patterns for some of the venoms also examined. 2. The results show that while there are considerable individual variations in the biological activities of many of the Bothrops venoms tested, there are some common characteristics at the genus and species levels. 3. The differences in the biological properties of the Bothrops venoms tested can be used for the differentiation of most Bothrops species examined.
A comparative study of the biological activities of venoms from snakes of the genus Agkistrodon (moccasins and copperheads)

Tan NH, Ponnudurai G

Comp. Biochem. Physiol., B, 1990;95(3):577-82.
PMID: 2158874

1. The hemorrhagic, procoagulant, anticoagulant, phosphodiesterase, alkaline phosphomonoesterase, 5'-nucleotidase, hyaluronidase, arginine ester hydrolase, phospholipase A, L-amino acid oxidase and protease activities of 31 samples of venom from three species of Agkistrodon (A. bilineatus, A. contortrix and A. piscivorus) and 10 venom samples from five other related species belonging to the same tribe of Agkistrodontini were examined. 2. The results indicate that interspecific differences in certain biological activities of the Agkistrodon venoms are more marked than individual variations of the activities, and that these differences can be used for differentiation of the species. Particularly useful for this purpose are the phosphodiesterase, arginine ester hydrolase and anticoagulant activities of the venoms. 3. Venoms of the subspecies of A. contortrix and A. piscivorus do not differ significantly in their biological activities.
A comparative study of the biological properties of venoms from snakes of the genus Vipera (true adders)

Tan NH, Ponnudurai G

Comp. Biochem. Physiol., B, 1990;96(4):683-8.
PMID: 2171867

1. The hemorrhagic, procoagulant, anticoagulant, phosphodiesterase, hyaluronidase, alkaline phosphomonoesterase, 5'-nucleotidase, arginine ester hydrolase, phospholipase A, L-amino acid oxidase and protease activities of 26 samples of venoms of 13 taxa of Vipera were determined and the Sephadex G-75 gel filtration patterns for some of the venoms were also examined. 2. The results indicate the presence of certain common characteristics among the venoms, particularly if V. russelli is excluded from the comparison. The results also support the recently proposed reassignment of V. russelli to a separate genus. 3. The data show that information on venom biological properties can be used for differentiation of venoms of many species of Vipera. Particularly useful for this purpose are the protease, phosphodiesterase, phospholipase A and the procoagulant activities and the Sephadex G-75 gel filtration patterns of the venoms.
Comparative study of the enzymatic, hemorrhagic, procoagulant and anticoagulant activities of some animal venoms

Tan NH, Ponnudurai G

Comp Biochem Physiol C Comp Pharmacol Toxicol, 1992 Oct;103(2):299-302.
PMID: 1360387

1. The enzymatic, hemorrhagic, procoagulant and anticoagulant activities of venoms of some animals including snakes, lizards, toads, scorpions, spider, wasps, bees and ants were compared. 2. Snake venom was the richest source of enzymes among the animal venoms. Most other animal venoms were devoid of phosphodiesterase, L-amino acid oxidase, alkaline phosphomonoesterase and acetylcholinesterase activities and only a few exhibited arginine ester hydrolase activity. These venoms, however, exhibited wide ranges of protease, 5'-nucleotidase and hyaluronidase activities. Most of the animal venoms examined exhibited some phospholipase A activity. 3. Other than snake venoms, only venoms of the toad Bufo calamita and the lizards were hemorrhagic, and only venoms of the social wasps, social bees and harvester ant exhibited strong anticoagulant activity. Procoagulant activity occurs only in snake venoms.
A comparative study of the biological properties of Dendroaspis (mamba) snake venoms

Tan NH, Arunmozhiarasi A, Ponnudurai G

Comp Biochem Physiol C Comp Pharmacol Toxicol, 1991;99(3):463-6.
PMID: 1685421

1. The biological properties of twelve samples of venoms from all four species of Dendroaspis (mamba) were investigated. 2. Dendroaspis venoms generally exhibited very low levels of protease, phosphodiesterase and alkaline phosphomonoesterase; low to moderately low level of 5'-nucleotidase and very high hyaluronidase activities, but were devoid of L-amino acid oxidase, phospholipase A, acetylcholinesterase and arginine ester hydrolase activities. The unusual feature in venom enzyme content can be used to distinguish Dendroaspis venoms from other snake venoms. 3. All Dendroaspis venoms did not exhibit hemorrhagic or procoagulant activity. Some Dendroaspis venoms, however, exhibited strong anticoagulant activity. The intravenous median lethal dose of the venoms ranged from 0.5 microgram/g mouse to 4.2 micrograms/g mouse. 4. Venom biological activities are not very useful for the differentiation of the Dendroaspis species. The four Dendroaspis venoms, however, can be differentiated by their venom SDS-polyacrylamide gel electrophoretic patterns.
A comparative study of the biological activities of rattlesnake (genera Crotalus and Sistrurus) venoms

Tan NH, Ponnudurai G

Comp Biochem Physiol C Comp Pharmacol Toxicol, 1991;98(2-3):455-61.
PMID: 1676959

1. The hemorrhagic, procoagulant, anticoagulant, protease, arginine ester hydrolase, phosphodiesterase, alkaline phosphomonoesterase, 5'-nucleotidase, hyaluronidase, phospholipase A and L-amino acid oxidase activities of 50 venom samples from 20 taxa of rattlesnake (genera Crotalus and Sistrurus) were examined. 2. The results show that notwithstanding individual variations in the biological activities of Crotalus venoms and the wide ranges of certain biological activities observed, there are some common characteristics at the genus and species levels. 3. The differences in biological activities of the venoms compared can be used for differentiation of the species. Particularly useful for this purpose are the thrombin-like enzyme, protease, arginine ester hydrolase, hemorrhagic and phospholipase A activities and kaolin-cephalin clotting time measurements.
A comparative study of the biological properties of krait (genus Bungarus) venoms

Tan NH, Ponnudurai G

Comp Biochem Physiol C Comp Pharmacol Toxicol, 1990;95(1):105-9.
PMID: 1971550

1. The intravenous median lethal doses (LD50), protease, phosphodiesterase, alkaline phosphomonoesterase, L-amino acid oxidase, acetylcholinesterase, phospholipase A, 5'-nucleotidase, hyauronidase and anticoagulant activities of fourteen samples of venoms from the four common species of krait (Bungarus caeruleus, Bungarus candidus, Bungarus multicinctus and Bungarus fasciatus) were examined. 2. The results indicate that even though there are individual variations in the biological properties of the krait venoms, interspecific differences in the properties can be used for differentiation of the venoms from the four species of Bungarus. Particularly useful for this purpose are the LD50's and the contents of 5'-nucleotidase and hyaluronidase of the venoms.
A comparative study of the biological properties of Australian elapid venoms

Tan NH, Ponnudurai G

Comp Biochem Physiol C Comp Pharmacol Toxicol, 1990;97(1):99-106.
PMID: 1981349

1. The hemorrhagic, procoagulant, anticoagulant, protease, phosphodiesterase, alkaline phosphomonoesterase, L-amino acid oxidase, acetylcholinesterase, arginine ester hydrolase, phospholipase A, 5'-nucleotidase and hyaluronidase activities of 39 samples of venoms from 13 species (15 taxa) of Australian elapids were determined and the Sephadex G-75 gel filtration patterns for some of the venoms were also examined. 2. The results indicate that Australian elapid venoms can be divided into two groups: procoagulant Australian venoms (including N. scutatus, N. ater, O. scutellatus, O. microlepidotus, P. porphyriacus, T. carinatus, H. stephensii and P. textilis) and non-procoagulant Australian venoms (including A. superbus, P. colletti, P. australis, P. guttatus and A. antarcticus). 3. The non-procoagulant Australian venoms exhibited biological properties similar to other elapid venoms, while the procoagulant Australian venoms exhibited some properties characteristic of viperid venoms. 4. The data show that information on venom biological properties can be used for differentiation of many species of Australian elapids. 5. Particularly useful for this purpose are the hyaluronidase, alkaline phosphomonoesterase, acetylcholinesterase, and the procoagulant activities and the Sephadex G-75 gel filtration patterns of the venoms.
Fulltext Melatonin promotes Schwann cell dedifferentiation and proliferation through the Ras/Raf/ERK and MAPK pathways, and glial cell-derived neurotrophic factor expression

Tiong YL, Ng KY, Koh RY, Ponnudurai G, Chye SM

Exp Ther Med, 2020 Nov;20(5):16.
PMID: 32934681 DOI: 10.3892/etm.2020.9143

Upon peripheral nerve injury (PNI), continuous proliferation of Schwann cells is critical for axon regeneration and tubular reconstruction for nerve regeneration. Melatonin is a hormone that is able to induce proliferation in various cell types. In the present study, the effects of melatonin on promoting Schwann cell proliferation and the molecular mechanism involved were investigated. The present results showed that melatonin enhanced the melatonin receptors (MT1 and MT2) expression in Schwann cells. Melatonin induced Schwann cell dedifferentiation into progenitor-like Schwann cells, as observed by immunofluorescence staining, which showed Sox2 marker expression. In addition, melatonin enhanced Schwann cell proliferation, mediated by the upregulation of glial cell-derived neurotropic factor (GNDF) and protein kinase C (PKC). Furthermore, the Ras/Raf/ERK and MAPK signaling pathways were also involved in Schwann cell dedifferentiation and proliferation. In conclusion, melatonin induced Schwann cell dedifferentiation and proliferation via the Ras/Raf/ERK, MAPK and GDNF/PKC pathways. The present results suggested that melatonin could be used to enhance the recovery of PNI.
Melatonin inhibits high glucose-induced ox-LDL/LDL expression and apoptosis in human umbilical endothelial cells

Tiong YL, Ng KY, Koh RY, Ponnudurai G, Chye SM

Horm Mol Biol Clin Investig, 2020 Jun 29;41(4).
PMID: 32598308 DOI: 10.1515/hmbci-2020-0009

BACKGROUND: Cardiovascular disease (CVD) is one of the major cause of mortality in diabetic patients. Evidence suggests that hyperglycemia in diabetic patients contributes to increased risk of CVD. This study is to investigate the therapeutic effects of melatonin on glucose-treated human umbilical vein endothelial cells (HUVEC) and provide insights on the underlying mechanisms.
MATERIALS AND METHODS: Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Reactive oxygen species (ROS) and membrane potential was detected using 2',7'-dichlorofluorescein diacetate and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1) dye staining, respectively. While, cell apoptosis was determined by Annexin-V staining and protein expression was measured using Western blot.
RESULTS: Our results suggested that melatonin inhibited glucose-induced ROS elevation, mitochondria dysfunction and apoptosis on HUVEC. Melatonin inhibited glucose-induced HUVEC apoptosis via PI3K/Akt signaling pathway. Activation of Akt further activated BcL-2 pathway through upregulation of Mcl-1 expression and downregulation Bax expression in order to inhibit glucose-induced HUVEC apoptosis. Besides that, melatonin promoted downregulation of oxLDL/LOX-1 in order to inhibit glucose-induced HUVEC apoptosis.
CONCLUSIONS: In conclusion, our results suggested that melatonin exerted vasculoprotective effects against glucose-induced apoptosis in HUVEC through PI3K/Akt, Bcl-2 and oxLDL/LOX-1 signaling pathways.
Fulltext Pre and post PBL meetings in ensuring the quality of facilitators in problem based learning

Amirthalingam SD, Ponnudurai G, Chen SY

International e-Journal of Science, Medicine & Education, 2010;4(2):47-53.
MyJurnal

Background: Problem based learning (PBL) is a student-centered curriculum delivery tool believed to promote active student participation. Though the PBL is student-centered, the facilitator plays an important role in maintaining the integrity of this system by providing balance in group interaction and discussion of learning issues. In International Medical University (IMU) one of the strategies to ensure the quality of the facilitators was the pre and post PBL meetings. This study aimed to gauge its usefulness in ensuring the quality of PBL facilitation.
Method: The questionnaire to study the perceptions of PBL facilitators on the pre and post PBL meetings included close ended questions on pre and post PBL meeting’s attendance and their scored opinion in improving PBL facilitation skills, open ended questions inviting suggestions to improve these meetings and PBL facilitation in IMU as a whole and self-evaluation as an effective PBL facilitator using a six point Likert scale to a list of statements.
Results: 84.2% of facilitators agreed the meetings were beneficial. Self-evaluation of their facilitator effectiveness showed on average ratings of seven out of ten indicating strong confidence in facilitating skills. Suggestions ensuring facilitator quality included content expert briefing in pre PBL meetings and student appraisals of facilitators given weightage in staff appraisal.
Conclusion: Pre and post PBL meetings enhanced facilitator comfort with the triggers, adding to their confidence and provided a venue to obtain feedback on the triggers.
Fulltext The levels of difficulty and discrimination indices in type a multiple choice questions of pre-clinical semester 1 multidisciplinary summative tests

Mitra, N.K., Nagaraja, H.S., Ponnudurai, G., Judson, J. P.

International e-Journal of Science, Medicine & Education, 2009;3(1):-.
MyJurnal

Item analysis is the process of collecting, summarizing and using information from students’ responses to assess the quality of test items. Difficulty index (P) and Discrimination index (D) are two parameters which help evaluate the standard of MCQ questions used in an examination, with abnormal values indicating poor quality. In this study, 120 test items of 12 Type A MCQ tests of Foundation 1 multi-disciplinary summative assessment from M2 / 2003 to M2 / 2006 cohorts of International Medical University were selected and their P-scores in percent and D-scores were estimated using Microsoft Office Excel. The relationship between the item difficulty index and discrimination index for each test item was determined by Pearson correlation analysis using SPSS 11.5. Mean difficulty index scores of the individual summative tests were in the range of 64% to 89%. One-third of total test items crossed the difficulty index of 80% indicating that those items were easy for the students. Sixty seven percent of the test items showed acceptable (> 0.2) discrimination index. Forty five out of 120 test items showed excellent discrimination index. Discrimination index correlated poorly with difficulty index (r = -0.325). In conclusion, a consistent level of test difficulty and discrimination indices was maintained from 2003 to 2006 in all the twelve summative type A MCQ tests.
Improving PBLs in the International Medical University: defining the 'good' PBL facilitator

Yee HY, Radhakrishnan A, Ponnudurai G

Med Teach, 2006 Sep;28(6):558-60.
PMID: 17074705

Students' perception of the role and characteristics of a good problem-based learning (PBL) facilitator were assessed in the same study in which students were exposed to the 'Flying a Kite Approach' to PBL. A pre-tested anonymous questionnaire addressed the good qualities of a facilitator as well as the negative aspects. Although faculty and students' perceptions of 'good 'and 'bad' attributes generally agreed, it is clear that students still prefer facilitators who talk more, i.e. explain unclear facts or correct them when their facts are wrong. Content experts are also preferred over non-content experts.

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