M.C.E. Gwee

Autonomic effects of some scorpion venoms and toxins.

1. The autonomic effects of venoms and toxins from several species of scorpions, including the Indian red scorpion Mesobuthus tamulus, the Chinese scorpion Buthus martensi Karsch and the Israeli scorpion Leiurus quinquestriatus quinquestriatus, all belonging to Buthidae, and the Asian black scorpions Heterometrus longimanus and Heterometrus spinifer, belonging to Scorpionidae, are reviewed.

Purification and partial characterization of stonustoxin (lethal factor) from Synanceja horrida venom.

1. The lethal factor of the stonefish (Synanceja horrida) venom, designated as the stonustoxin, was purified to homogeneity by a two-step procedure on Sephacryl S-200 High Resolution (HR) gel permeation and DEAE Bio-Gel A anion exchange chromatography. 2. Stonustoxin has a native mol. wt of 148,000 and an isoelectric point of 6.9. 3. SDS-polyacrylamide gel electrophoresis revealed two subunits (designated alpha and beta) with mol. wts of 71,000 and 79,000, respectively. 4. The amino acid composition of both subunits and the N-terminal amino acid sequence of the beta subunit were also determined. 5. Purified stonustoxin had an LD50 of 0.017 microgram/g which is 22-fold more potent than that of the crude venom. 6. The toxin exhibited potent haemolytic activity in vitro and edema-inducing activity with a minimum edema dose (MED) of 0.15 micrograms in mouse paw. The edema effect was not antagonized by diphenhydramine.

A review of stonefish venoms and toxins

Venoms from stonefish (genus Synanceja) have marked effects on the cardiovascular and neuromuscular systems and on vascular permeability; the venoms also exhibit haemolytic and hyaluronidase activity. Recently, a toxic protein, stonustoxin (SNTX), was purified from the venom of S. horrida: the primary lethal action of SNTX has been attributed to its potent endothelium-dependent vasorelaxant activity causing a rapid, marked and irreversible hypotension; the other actions of SNTX resemble those of the stonefish crude venoms.

GLOBALIZATION OF PROBLEM-BASED LEARNING (PBL): CROSS-CULTURAL IMPLICATIONS

Problem-based learning (PBL) is essentially a learning system design that incorporates several educational strategies to optimize student-centered learning outcomes beyond just knowledge acquisition. PBL was implemented almost four decades ago as an innovative and alternative pathway to learning in medical education in McMaster University Medical School. Since then, PBL has spread widely across the world and has now been adopted globally, including in much of Asia. The globalization of PBL has important cross-cultural implications. Delivery of instruction in PBL involves active peer teaching-learning in an open communication style. Consequently, this may pose an apparent serious conflict with the Asian communication style generally dominated by a cultural reticence. However, evidence available, especially from the PBL experience of some senior Korean medical students doing an elective in the University of Toronto Medical School and the cross-cultural PBL experience initiated by Kaohsiung Medical University, strongly suggests creating a conducive and supportive learning environment for students learning in a PBL setting can overcome the perceived cultural barriers; that is, nurture matters more than culture in the learning environment. Karaoke is very much an Asian initiative. The Karaoke culture and philosophy provide a useful lesson on how to create a conducive and supportive environment to encourage, enhance and motivate group activity. Some key attributes associated with Asian culture are in fact consistent with, and aligned to, some of the basic tenets of PBL, including the congruence between the Asian emphasis on group before individual interest, and the collaborative small group learning design used in PBL. Although there are great expectations of the educational outcomes students can acquire from PBL, the available evidence supports the contention the actual educational outcomes acquired from PBL do not really match the expected educational outcomes commonly intended and specified for a PBL program. Proficiency in the English language can pose serious problems for some Asian medical schools, which choose to use English as the language for discussion in PBL tutorials. A novel approach that can be applied to overcome this problem is to allow students to engage in discussions using both their native language as well as English, a highly successful practice implemented by the University of Airlangga, Surabaya, Indonesia. As PBL is a highly resource-intensive pedagogy, Asian medical educators need to have a clear understanding of the PBL process, philosophy and practice in order to be able to optimize the educational outcomes that can be derived from a PBL curriculum.Problem‐based learning (PBL) is essentially a learning system design that incorporates several educational strategies to optimize student‐centered learning outcomes beyond just knowledge acquisition. PBL was implemented almost four decades ago as an innovative and alternative pathway to learning in medical education in McMaster University Medical School. Since then, PBL has spread widely across the world and has now been adopted globally, including in much of Asia. The globalization of PBL has important cross‐cultural implications. Delivery of instruction in PBL involves active peer teaching‐learning in an open communication style. Consequently, this may pose an apparent serious conflict with the Asian communication style generally dominated by a cultural reticence. However, evidence available, especially from the PBL experience of some senior Korean medical students doing an elective in the University of Toronto Medical School and the cross‐cultural PBL experience initiated by Kaohsiung Medical University, strongly suggests creating a conducive and supportive learning environment for students learning in a PBL setting can overcome the perceived cultural barriers; that is, nurture matters more than culture in the learning environment. Karaoke is very much an Asian initiative. The Karaoke culture and philosophy provide a useful lesson on how to create a conducive and supportive environment to encourage, enhance and motivate group activity. Some key attributes associated with Asian culture are in fact consistent with, and aligned to, some of the basic tenets of PBL, including the congruence between the Asian emphasis on group before individual interest, and the collaborative small group learning design used in PBL. Although there are great expectations of the educational outcomes students can acquire from PBL, the available evidence supports the contention the actual educational outcomes acquired from PBL do not really match the expected educational outcomes commonly intended and specified for a PBL program. Proficiency in the English language can pose serious problems for some Asian medical schools, which choose to use English as the language for discussion in PBL tutorials. A novel approach that can be applied to overcome this problem is to allow students to engage in discussions using both their native language as well as English, a highly successful practice implemented by the University of Airlangga, Surabaya, Indonesia. As PBL is a highly resource‐intensive pedagogy, Asian medical educators need to have a clear understanding of the PBL process, philosophy and practice in order to be able to optimize the educational outcomes that can be derived from a PBL curriculum.

Neuromuscular effects of candoxin, a novel toxin from the venom of the Malayan krait (Bungarus candidus)

Candoxin (MW 7334.6), a novel toxin isolated from the venom of the Malayan krait Bungarus candidus, belongs to the poorly characterized subfamily of nonconventional three‐finger toxins present in Elapid venoms. The current study details the pharmacological effects of candoxin at the neuromuscular junction. Candoxin produces a novel pattern of neuromuscular blockade in isolated nerve‐muscle preparations and the tibialis anterior muscle of anaesthetized rats. In contrast to the virtually irreversible postsynaptic neuromuscular blockade produced by curaremimetic α‐neurotoxins, the neuromuscular blockade produced by candoxin was rapidly and completely reversed by washing or by the addition of the anticholinesterase neostigmine. Candoxin also produced significant train‐of‐four fade during the onset of and recovery from neuromuscular blockade, both, in vitro and in vivo. The fade phenomenon has been attributed to a blockade of putative presynaptic nicotinic acetylcholine receptors (nAChRs) that mediate a positive feedback mechanism and maintain adequate transmitter release during rapid repetitive stimulation. In this respect, candoxin closely resembles the neuromuscular blocking effects of d‐tubocurarine, and differs markedly from curaremimetic α‐neurotoxins that produce little or no fade. Electrophysiological experiments confirmed that candoxin produced a readily reversible blockade (IC50∼10 nM) of oocyte‐expressed muscle (αβγδ) nAChRs. Like α‐conotoxin MI, well known for its preferential binding to the α/δ interface of the muscle (αβγδ) nAChR, candoxin also demonstrated a biphasic concentration–response inhibition curve with a high‐ (IC50∼2.2 nM) and a low‐ (IC50∼98 nM) affinity component, suggesting that it may exhibit differential affinities for the two binding sites on the muscle (αβγδ) receptor. In contrast, curaremimetic α‐neurotoxins have been reported to antagonize both binding sites with equal affinity.

Problem-Based Learning: A Strategic Learning System Design For The Education Of Healthcare Professionals in the 21ST Century

Problem‐based learning (PBL) was first implemented by McMaster University medical school in 1969 as a radical, innovative, and alternative pathway to learning in medical education, thus setting a new educational trend. PBL has now spread widely across the globe and beyond the healthcare disciplines, and has prevailed for almost four decades. PBL is essentially a strategic learning system design, which combines several complementary educational principles for the delivery of instruction. PBL is specifically aimed at enhancing and optimizing the educational outcomes of learner‐centered, collaborative, contextual, integrated, self‐directed, and reflective learning. The design and delivery of instruction in PBL involve peer teaching and learning in small groups through the social construction of knowledge using a real‐life problem case to trigger the learning process. Therefore, PBL represents a major shift in the educational paradigm from the traditional teacher‐directed (teacher‐centered) instruction to student‐centered (learner‐centered) learning. PBL is firmly underpinned by several educational theories, but problems are often encountered in practice that can affect learning outcomes. Educators contemplating implementing PBL in their institutions should have a clear understanding of its basic tenets, its practice and its philosophy, as well as the issues, challenges, and opportunities associated with its implementation. Special attention should be paid to the training and selection of PBL tutors who have a critical role in the PBL process. Furthermore, a significant change in the mindsets of both students and teachers are required for the successful implementation of PBL. Thus, effective training programs for students and teachers must precede its implementation. PBL is a highly resource‐intensive learning strategy and the returns on investment (i.e. the actual versus expected learning outcomes) should be carefully and critically appraised in the decision‐making process. Implementation of PBL can be a daunting task and will require detailed and careful planning, together with a significant commitment on the part of educators given the responsibility to implement PBL in an institution. PBL can offer a more holistic, value‐added, and quality education to energize student learning in the healthcare professions in the 21st century. Successful implementation of PBL can therefore help to nurture in students the development of desired ‘habits of mind, behavior, and action’ to become the competent, caring, and ethical healthcare professionals of the 21st century. Thus, PBL can contribute to the improvement of the healthcare of a nation by healthcare professionals, but we need to do it right.

Stonustoxin : effects on neuromuscular function in vitro and in vivo

Stonustoxin (8-50 micrograms/ml) produced a rapid and concentration-dependent rise in tension (contracture) of the electrically stimulated mouse hemidiaphragm followed by a gradual waning of tension from the peak to the baseline; the nerve-evoked and the directly (muscle)-evoked twitches of the hemidiaphragm were also progressively and irreversibly blocked in a time- and concentration-dependent manner. Stonustoxin (22 and 44 micrograms/ml) produced a similar rapid rise in tension of the chick biventer cervicis muscle as well as irreversible and concentration-dependent blockade of nerve-evoked twitches and contractures produced by acetylcholine (200 microM), carbachol (8 microM) and KCl (40 mM). The muscle contracture produced by stonustoxin was blocked by dantrolene sodium (6 microM) but not by tubocurarine (15 microM). Moreover, stonustoxin (40 micrograms/ml) did not inhibit nerve conduction in the toad sciatic nerve and stonustoxin (60 micrograms/ml) did not exhibit any anticholinesterase activity. The inhibition of neuromuscular function by stonustoxin in the mouse hemidiaphragm and chick biventer cervicis muscle can therefore be attributed to some irreversible myotoxic action(s) of the toxin, whereas the stonustoxin-induced muscle contractures could have been mediated via depolarization of muscle fibres.

FREE CHOLINE CONCENTRATION AND CEPHALIN‐N‐METHYLTRANSFERASE ACTIVITY IN THE MATERNAL AND FOETAL LIVER AND PLACENTA OF PREGNANT RATS

1. The concentration of free choline and cephalin‐N‐methyltransferase activity of the maternal and foetal liver and placenta of rats in late pregnancy were determined.

Makatoxin I, a Novel Toxin Isolated from the Venom of the Scorpion Buthus martensi Karsch, Exhibits Nitrergic Actions

Buthus martensi Karsch venom exhibits nitrergic action in rat anococcygeus muscle (ACM). We have purified a novel toxin, makatoxin I (MkTx I), which exhibits nitrergic action, to homogeneity from this venom by a combination of gel-filtration, cation-exchange chromatography, and reverse-phase chromatography. Its purity was assessed by capillary electrophoresis and mass spectrometry. Its molecular weight was found to be 7031.71 ± 2.88 as calculated from electrospray mass spectrographic data. The complete amino acid sequence was elucidated by sequencing of reduced and S-pyridylethylated toxin and a carboxyl-terminal peptide, P55-64, generated by the cleavage of toxin with endoproteinase Lys-C. The complete sequence of MkTx I is GRDAYIADSENCTYTCALNPYCNDLCTKNGAKSGYCQWAGRYGNACWCIDLPDKVPIRISGSCR. This toxin is composed of 64 amino acid residues and contains 8 half-cystine residues. Structurally, MkTx I has high similarity to Bot I and Bot II when compared with toxins from other scorpion species. The effects of MkTx I on nitrergic responses were investigated using the rat isolated ACM mounted in Krebs solution (37 °C, 5% CO2 in O2). MkTx I (2 μg/ml) markedly relaxed the carbachol-precontracted ACM; the relaxation was inhibited by the stereoselective inhibitor of nitric oxide synthase, Nω-nitro-L-arginine methyl ester (50 μM). Thus, MkTx I is the first α-toxin that can mediate nitrergic responses in the rat isolated ACM.

Teaching of medical pharmacology: The need to nurture the early development of desired attitudes for safe and rational drug prescribing

Pharmacology, as a basic medical science discipline, provides the scientific basis of therapeutics, i.e. the scientific foundation for safe and rational prescribing of drugs. The public, lay media, and the medical profession have raised serious concerns over the high incidence of errors of drug prescribing which compromise patient safety, including death of some patients, attributed mainly to inadequate teaching of medical pharmacology and, consequently, to medical graduates lacking skills in safe and effective drug prescribing. There is also overwhelming evidence that the pervasive and prevalent doctor–drug industry relationships have a strong influence over the prescribing habits and drug education of doctors. The British Pharmacological Society and American Association of Medical Colleges have crafted some insightful guidelines, including the learning of desired attitudes, for designing a medical pharmacology curriculum aimed at enhancing patient safety. This article will critically review the major issues relating to errors of drug prescribing, including the need to nurture the early development of desired attitudes which foster safe and rational drug prescribing. A simple educational approach, using a task analysis of drug prescribing, is applied to identify desired attitudes which should be incorporated into a basic pharmacology course for medical students in the twenty-first century.