Lathyrism

Sixteen patients with lathyrism, age ranging between 18 and 55 years and duration of illness between 2 and 25 years, underwent H reflex studies with the aim of studying motor neurone excitability. The patients had marked spasticity (Ashworth score ranging between 2 and 5) and mild to moderate leg weakness. Knee and ankle reflexes were exaggerated in all and the plantar response was extensor in 14 patients. The H reflex abnormalities included increased HM ratio indicating increased motoneurone excitability, significant lack of vibratory inhibition indicating altered transmission in the premotoneuronal portion of the H reflex pathway, and lack of reciprocal inhibition (P < 0.01). These H reflex abnormalities were not related to spasticity, weakness, clonus or plantar response. The H reflex recovery curve in 6 patients revealed increased excitability throughout the recovery curve. The secondary facilitation started and peaked slightly earlier than normal, and the late depression was...

Single-chemical and mixture concentration-response curves generated using a frog embryo model were examined for value in assessing
whether chemicals exert toxic effects at the same or at different molecular sites of action. Toxicity tests were conducted on a series of
osteolathyrogens, i.e. chemicals that inhibit cross-linking of developing connective tissue fibers. Induction of osteolathyrism, which manifests
as lesions in the notochord of exposed tadpoles, has several possible molecular sites of action, including agent-cofactor reactivity during the
enzyme-mediated cross-linking process. UV-VIS spectrophotometry of osteolathyrogen-cofactor reactivity (i.e. in vitro analysis) was coupled
with the 96-h frog embryo mixture toxicity assay (i.e. in vivo toxicity) to compare molecular sites of action for several osteolathyrogens with
the combined osteolathyritic effects of the agents. Single-chemical concentration-response curves were used to calculate theoretical curves for
the dose-addition model of combined effect. Slope and EC50 values for both theoretical and experimental mixture curves were then generated to
statistically examine the hypothesis that agents with shared sites of action have dose-response curve (DRC) slopes that are similar when given
alone and in combination, and slope and EC50 values that, when administered together, are consistent with those calculated for dose-addition.
For combinations of cofactor-binding agents (semicarbazide, thiosemicarbazide, aminoacetonitrile), slope values were generally similar with
additivity quotients near 1.0 (1.0=dose-additive) and combined osteolathyritic effects that were consistent with dose-addition. None of these
were true for combinations that included agents that did not show rapid cofactor binding (
-aminopropionitrile, methyleneaminoacetonitrile).
The results suggest that DRC analysis could be a useful tool for delineating common or different molecular sites of toxic action and that the
approaches used warrant further study for evaluating the mechanistic basis for combined effects of toxicants

Habituated callus tissues derived from leaf explants of Lathyrus sativus L. (grass pea) were cultured under different environmental conditions such as drought, salinity and deficiency or oversupply of micronutrients. The biosynthesis of the neuro-excitatory β-ODAP (β-N-oxalyl-L-α,β-diaminopropionic acid) was induced by feeding the precursor BIA, (β-isoxazolin-5-on-2-yl)-alanine, to those calli habituated under different stress conditions. Conversion of BIA into β-ODAP was reduced by Zn(2+) at different levels of Fe(2+) supplements while excess of Fe(2+) enhanced it at different Zn(2+) levels in the media. The biosynthesis of β-ODAP was increased by both oversupply and deficiency of Mn(2+) manganese while B(3+) as well as Co(2+) increased it significantly by oversupply. Al(3+) enhanced the conversion of BIA into β-ODAP significantly in a concentration-dependent way. Cu(2+) also reduced the formation of β-ODAP when increased in the media. Mo(6+) had no apparent effect. NaCl decreased the conversion of BIA into β-ODAP proportionately with the increase in salinity. β-ODAP was increased with increasing mannitol concentration till -0.23MPa while at this osmotic potential created with PEG-20,000 the formation of β-ODAP is completely inhibited in low toxin calli. These experiments demonstrate the importance of environmental factors, especially micronutrients and salinity, on the biosynthesis of β-ODAP.

BACKGROUND Neurolathyrism is a toxic nutritional disorder caused by consumption of the grass pea, Lathyrus sativus. The disease, which manifests as an acute or insidiously evolving spastic paraparesis, continues to occur throughout Africa and Asia. Research on this disease is limited, and to our knowledge no imaging studies of patients with neurolathyrism have been published. OBJECTIVES To better localize the site of damage in neurolathyrism using advanced imaging methods. METHODS Three male patients, immigrants from Ethiopia, were included in the study. All had a history of arrested spastic paraparesis that had evolved before their emigration from Ethiopia, and a past history of exposure to grass pea without any other cause. Functional magnetic resonance imaging (fMRI) included simple motor tasks to evaluate cortical motor areas. Anatomic scans included diffusion tensor imaging (DTI) to evaluate the corticospinal tracts. RESULTS In all patients clear activation was found in motor r...

The presence of an enzyme(s) associated with purified tropoelastin has been established. Results indicate that the enzyme(s) remains closely associated with the soluble elastin throughout the entire purification procedure suggesting that it is very tightly bound. Enzymatic activity is optimum through the pH range 7–9 (37 °C) and can be inhibited by disodium ethylenediaminetetraacetate, N-ethylmaleimide, sulfite, soybean trypsin inhibitor and human α-l-antitrypsin. The fragmentation pattern appears to be specific and reproducible.

Habituated callus tissues derived from leaf explants of Lathyrus sativus L. (grass pea) were cultured under different environmental conditions such as drought, salinity and deficiency or oversupply of micronutrients. The biosynthesis of the neuro-excitatory β-ODAP (β-N-oxalyl-L-α,β-diaminopropionic acid) was induced by feeding the precursor BIA, (β-isoxazolin-5-on-2-yl)-alanine, to those calli habituated under different stress conditions. Conversion of BIA into β-ODAP was reduced by Zn(2+) at different levels of Fe(2+) supplements while excess of Fe(2+) enhanced it at different Zn(2+) levels in the media. The biosynthesis of β-ODAP was increased by both oversupply and deficiency of Mn(2+) manganese while B(3+) as well as Co(2+) increased it significantly by oversupply. Al(3+) enhanced the conversion of BIA into β-ODAP significantly in a concentration-dependent way. Cu(2+) also reduced the formation of β-ODAP when increased in the media. Mo(6+) had no apparent effect. NaCl decreased ...

Neurolathyrism is a non progressive motor neuron disorder engendered by the prolonged over-consumption of Lathyrus sativus (grass pea) seeds which contain a neurotoxic amino acid, β-N oxalyl- L-α, β-diaminopropionic acid (β-ODAP). It is characterized by spastic paraparesis in the hind limbs. The present study was conducted in 105 households (HHs) of Gondia district in Maharashtra, India, where grass pea is cultivated and consumed to assess the health implication of its consumption. Across-sectional survey was carried out in 105 HHS in five villages and grass pea samples were collected for β-ODAP estimation. Amino acid analysis was also done, neurolathyrism cases were identified by snowball sampling method and neurological examination was carried out. The study revealed that 61 per cent of population was consuming this pulse as a part of diet. β-ODAP concentration in grass pea was high in Bora village (1254.5 ± 528.21 mg %) and less in Malgaon village (413.6±415.79 mg %). The nutriti...

Environmental chemicals involved in the etiology of human neurodegenerative disorders are challenging to identify. Described here is research designed to determine the etiology and molecular pathogenesis of nerve cell degeneration in two little known corticomotoneuronal diseases with established environmental triggers. Both conditions are toxic-nutritional disorders dominated by persistent spastic weakness of the legs and degeneration of corresponding corticospinal pathways. Lathyrism, a disease caused by dietary dependence on grass pea (Lathyrus sativus), is mediated by a stereospecific plant amino acid (beta-N-oxalylamino-L-alanine) that serves as a potent agonist at the (RS)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) subclass of neuronal glutamate receptors. A neurologically similar disorder, konzo ("tied legs"), is found among protein-poor African communities that rely for food on cyanogen-containing cassava roots. Thiocyanate, the principal metabolite of cyanide, is an attractive etiologic candidate for konzo because it selectively promotes the action of glutamate at AMPA receptors. Studies are urgently needed to assess the health effects of cassava and other cyanogenic plants, components of which are widely used as food.

Purified chick skin collagen constituent chains were examined for the content of the aldol condensation product of two residues of α-aminoadipic δ-semialdehyde after reduction with NaBT4 and alkali hydrolysis. The single chains, α1 and α2, contained none whereas their cross-linked dimer, β12, contained one equivalent. These findings were confirmed by the similar studies performed on the peptides derived from the cross-link region of collagen by CNBr cleavage. Data presented here strongly indicate that the aldol condensation product is the intramolecular cross-link.