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Do We Need More Research on Neurolathyrism? S.L.N

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Do We Need More Research on Neurolathyrism? S.L.N Volume 2 (1), March 2001 Edited by Colin Hanbury, CLIMA, Australia Jointly supported by Lathyrus Lathyrism Newsletter 2 (2001) CONTENTS Page Editor's Comment 1 Colin Hanbury -Australia Articles Opinion and Future Directions 2 Do we need more research on neurolathyrism? S.L.N. Rao -India 5 Vapniarca revisited: Lessons from an inhuman human Fernand Lambein, Delphin Diasolua Ngudi, experience. Yu-Haey Kuo -Belgium Food Processing 8 Fermentation of teff (Eragrostis tef), grass-pea (Lathyrus Y. Yigzaw, L. Gorton, G. Akalu, T. Solomon sativus), and their mixtures: Aspects of nutrition and food –Sweden and Ethiopia safety. Neurology 11 Similarities between Tropical Spastic Paraparesis (TSP) Vladimir Zanonivic -Colombia and neurolathyrism Plant Genetic Resources, Evaluation and Breeding 15 Electrophoretic phenotypes of different enzymes in some E. Alba, G. B. Polignano, D. De Carlo, A. entries of Lathyrus sativus L. Mincione -Italy 21 Autogamy and allogamy in genus Lathyrus. N. Ben Brahim, D. Combes, M. Marrakchi – Tunisia and France 27 Evaluation of selected traits in grasspea (Lathyrus sativus Michaela Benková, Mária Žáková –Slovak L.) genetic resources. Republic 31 Morphological characterisation of Spanish genetic L. De la Rosa, I. Martín -Spain resources of Lathyrus sativus L. 35 Protoplast, cell and tissue cultures for the biotechnological S. Ochatt, P. Durieu, L. Jacas, C. Pontécaille breeding of grass pea (Lathyrus sativus L.) -France 39 Progress in isolation and purification of Lathyrus sativus M. Anisur Rahman, M. Matiur Rahman, M. breeding lines Akhtaruzzaman Sarkar -Bangladesh 41 Mutants of grasspea (Lathyrus sativus L.) obtained after Wojciech Rybinski -Poland use of chemomutagens- Abstract 42 Development of low ODAP somaclones of Lathyrus I.M. Santha, S.L. Mehta -India sativus.- Abstract. 43 Isozymes variability of grasspea (Lathyrus sativus L.) in Wuletaw Tadesse, Endashaw Bekele - Ethiopia. Ethiopia Lathyrus Lathyrism Newsletter 2 (2001) Agronomy 47 Effect of foliar spray of potassium nitrate and calcium R.K. Sarkar, G.C. Malik -India nitrate on grasspea (Lathyrus sativus L.) grown in rice fallows. Animal Feeding 49 The nutritional value of Lathyrus cicera and Lupinus Colin White, Colin Hanbury, Kadambot angustifolius grain for sheep- Summary Siddique -Australia 51 Recent Publications 53 Items of Interest The Lathyrus Lathyrism Newsletter can be obtained on-line at http://go.to/lathyrus OR http://www.clima.uwa.edu.au/lathyrus All research articles are provided there in pdf format. Jointly supported by: Centre for Legumes in Mediterranean Agriculture (CLIMA), University of Western Australia, 35 Stirling Highway Crawley 6009, Australia http://www.clima.uwa.edu.au and Third World Medical Research Foundation (TWMRF), PO Box 9171, Portland, Oregon 97207, USA http://www.twmrf.org Lathyrus Lathyrism Newsletter 2 (2001) EDITOR’S COMMENT Welcome to the second edition of the revived Any comments on improving the newsletter in the Lathyrus Lathyrism Newsletter. Thank you to all the future or any other suggestions are very welcome, authors who have contributed their work. This contributions from readers are imperative to volume will be in two parts, this edition is the first maintaining the direction and momentum of the [Vol. 2(1)], the second part [Vol. 2(2)] will follow in newsletter. Most research submissions should be September/October 2001. If you wish to contribute an approximately 1500 words and can include a small article for the coming edition it will be still possible number of tables or figures, photographs of the to include some that arrive by 15 September 2001. I author and of research are encouraged as they are will however be away from 23 July until 14 easily included in the on-line version. September. Please also note that my Email address Introduction/Methods/Results and Discussion are the will be changing shortly, although I hope to continue preferred layout for research summaries, although with both old and new addresses for some time. I do this can be altered as necessary. Abstracts are also not know the new Email address at this time. welcome, if they have been published elsewhere then full acknowledgment will be made. Electronic copies One of the aims of the newsletter has been to increase are preferred but not essential. cooperation across disciplines and distance and this seems to be occurring already. I for one have a greater understanding of what has been recently achieved in areas other than my own. Authors Colin Hanbury working in all disciplines are encouraged to submit work relevant to Lathyrus and lathyrism. Please see the section “Items of Interest” (page 53) on the Lathyrus Email group. If you have Email access this will provide you with ready Editor contact details: communication to so far 40 other researchers Dr Colin Hanbury worldwide, all interested people are welcome to join. Centre for Legumes in Mediterranean Agriculture (CLIMA) Thanks is due to the Centre for Legumes in University of Western Australia Mediterranean Agriculture (CLIMA) and the Third 35 Stirling Highway, Nedlands 6009 World Medical Research Foundation (TWMRF) for Australia supporting the newsletter. Email: [email protected] _____________________________________________________________________________________________ 1 Lathyrus Lathyrism Newsletter 2 (2001) Do we need more research on than ODAP (6). Even if one were to consider agonistic neurolathyrism? activity of ODAP at glutamate receptors as a plausible mechanism of toxicity, it simply cannot explain the S.L.N. Rao extreme species differences in susceptibility to ODAP. Thus can the adult rat and the BALB/c mice which are Department of Biochemistry resistant to ODAP possess a different disposition of Osmania University, Hyderabad-500 007, India glutamate receptor subpopulations than the susceptible species the chick? Vexed by this inconsistency, we Email: [email protected] came up with the most surprising finding that the C57BL6J black mice are easily susceptible to ODAP It is nearly four decades since the discovery of ODAP while the BALB/c white mice are resistant to it but as the major neurotoxic constituent of Lathyrus sativus would become susceptible if pretreated with tyrosine seeds. However, several basic questions relating to (3). This, further led us to establish the first ever neurolathyrism still remain unanswered. We are stereospecific inhibition of an enzyme activity by unable to convince several governments to ban the ODAP, namely, that of tyrosine aminotransferase. cultivation of the pulse and to take on a more serious Over the years we have been so enamoured by the approach to introducing the low toxin varieties. "structural relatedness" of ODAP with glutamate that Meanwhile, farmers continue to grow the traditional no one dreamt that it may inhibit the aromatic amino varieties and the consumption of the pulse continues. acid transferase. Our molecular modelling studies with We still do not have a straightforward method to ODAP (to be published) show that ODAP is indeed produce a convincing animal model to study the conformationally cognate more with tyrosine and less disease. We do not even have an acceptable with glutamate (Fig. 1). We have shown that ODAP mechanism for the toxicity of ODAP. While we are administration results in a significant increase in brain concerned that the disease affects the poorest of the dopa and dopamine levels, only in black mice, as a poor, we do not know how the majority of the fallout of TAT inhibition and not in white mice. Lathyrus consuming population escape from the Further studies are needed to pinpoint the toxic disease. The precise enzymatic pathway and its metabolites of dopa and dopamine that may be the real characterisation for the biosynthesis of ODAP are still culprits of neurotoxicity as a result of oxidative needed before genetic engineering principles can be damage (3). applied to produce genetically modified ODAP free Lathyrus. It is rather intriguing how these seemingly One of the more puzzling features of neurolathyrism simple questions relating to a human disease of relates to how and why a large majority of the nutritional origin remain unsolved. I am certain that Lathyrus consuming subjects escape from the disease, there are reasons that most Lathyrus researchers would which is quite evident even in the recent Ethiopian agree upon. epidemic. To my knowledge, no one has attempted to explain this feature although some newer thoughts ODAP is deceptively a dicarboxylic amino acid appear to be emerging in evaluating the incidence of chemically related to glutamate (aspartate). However, the disease. Since most laboratory animal studies, to date, no direct effect of ODAP on any of the including those with monkeys, show that orally enzymes associated with the metabolism of either administered ODAP is excreted in the urine largely glutamate or aspartate has been demonstrated and also unchanged, it has generally been assumed that ODAP it does not have any substrate activity with any of would have a similar fate in humans. I would like to these enzymes. A number of studies have shown that share some of our recent yet unpublished findings on ODAP acts as an agonist at the AMPA preferring this aspect. In a survey of a Lathyrus consuming glutamate receptors (5,7). But in spite of our best population, the overnight urine samples collected efforts, we have been unable to demonstrate any following a Lathyrus meal showed very little urinary significant specific binding of 3H ODAP to synaptic excretion of ODAP (less than 2-5%), this was membranes of the chick or rat (1). This crucial evidence confirmed on several occasions. We have confirmed thus fails to establish antagonistic property for ODAP this finding in controlled studies with human at glutamate receptors. Moreover, we have now shown volunteers wherein the ODAP excretion was less than that even free diaminopropionate (DAP) and 1% of the dietarily consumed ODAP. This suggests carboxymethyl DAP (CMDAP) another synthetic that, as opposed to the findings in experimental glutamate/ODAP analogue which are non-neurotoxic animals, humans have an ability to (acute study) exhibit a far greater excitotoxic potential metabolise/detoxify orally ingested ODAP.
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