[Research in Motor Neuron Diseases Caused by Natural Substances: Focus on Pathological Mechanisms of Neurolathyrism].

Diseases of the motor-conducting system that cause moving disability affect socio-economic activity as well as human dignity. Neurolathyrism, konzo, and amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC) have attracted researchers to study the pathology of motor neuron (MN) diseases such as ALS. I have been studying neurolathyrism, which is caused by overconsumption of a legume grass pea (Lathyrys sativus L.). Among people who consume the legume as a food staple, many developed life-long paraparesis in their legs. ß-N-oxalyl-l-α,ß- diaminopropionic (l-ß-ODAP; BOAA), contained in this plant, is a neurotoxic analog of l-glutamic acid. We have clarified that in addition to the causal involvement of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamatergic receptor in MN death, a toxic role of group I metabotropic glutamate receptors as well as transient receptor potential channels were involved in the MN insult by l-ß-ODAP using primary MN culture. We have also established a neurolathyrism rat model by repeated, peripheral l-ß-ODAP treatment to newborn rats under mild stress. Rats showing hind-leg paraparesis with an incidence rate of around 25% were useful to study the in vivo pathology of MN disease. MNs of these rats were greatly decreased at their lumbo/sacral segments at various ages. Intra-parenchymal hemorrhage was consistently observed in paraparetic rats but not in cripple-free, treated rats. MN were depleted even at an acute period around bleeding spots, suggesting catastrophic neuro-vascular-glial interaction in this MN disease. Summaries of konzo and ALS-PDCs studies are also introduced.

Determination of ß-N-oxalyl-L-α,ß-diaminopropionic acid and homoarginine in Lathyrus sativus and Lathyrus cicera by capillary zone electrophoresis.

BACKGROUND: Lathyrus species as legumes represent an alternative protein source for human and animal nutrition. Heavy consumption of these species can lead to lathyrism, caused by the non-protein amino acid ß-N-oxalyl-l-α,ß-diaminopropionic acid (ß-ODAP). Currently, there is no well-defined level below which ß-ODAP is considered non-toxic. In this work, the ß-ODAP content was determined in L. sativus and L. cicera samples to assess their potential toxicity. Homoarginine is another non-protein amino acid found in Lathyrus spp. with interesting implications for human and animal nutrition. RESULTS: The level of ß-ODAP found in these two species ranged from 0.79 to 5.05 mg g(-1). The homoarginine content of the samples ranged from 7.49 to 12.44 mg g(-1). CONCLUSION: This paper describes an accurate, fast and sensitive method of simultaneous detection and quantification of ß-ODAP and homoarginine by capillary zone electrophoresis in L. cicera and L. sativus seeds. Moreover, several methods of extraction were compared to determine the highest performance.

Occupational rhinoconjunctivitis and asthma by exposure to Lathyrus sativus flour.

We report the case of a 42-year-old non-smoking man, who had worked as a carpenter for 6 years and who reported a history of rhinorrhea, paroxysmal sneezing, nasocular pruritus, lacrimation, wheezing and dyspnea attacks while preparing a mixture to seal the junctures between wooden panels. Allergy study consisted of skin prick testing (SPT) to inhalants, foods and Lathyrus sativus flour (LSF) extract, specific bronchial provocation test with LSF extract, cytological analysis of sputum, specific IgE antibodies against LSF, and histamine releasing test with dilutions (1:5, 1:25, 1:125, 1:625) of LSF. The results demonstrated occupational rhinoconjunctivitis and asthma due to LSF exposure. We provide a review of published reports to date.

Occupational rhinoconjunctivitys and asthma by exposure to Lathyrus sativus flour

We report the case of a 42-year-old non-smoking man, who had worked as a carpenter for 6 years and who reported a history of rhinorrhea, paroxysmal sneezing, nasocular pruritus, lacrimation, wheezing and dyspnea attacks while preparing a mixture to seal the junctures between wooden panels. Allergy study consisted of skin prick testing (SPT) to inhalants, foods and Lathyrus sativus flour (LSF) extract, specific bronchial provocation test with LSF extract, cytological analysis of sputum, specific IgE antibodies against LSF, and histamine releasing test with dilutions (1:5, 1:25, 1:125, 1:625) of LSF. The results demonstrated occupational rhinoconjunctivitis and asthma due to LSF exposure. We provide a review of published reports to date

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Occupational asthma caused by grass pea used in the industrial processing of parquet.

BACKGROUND: although grass pea belongs to the leguminoseae family, allergic reactions to its flour have rarely been described. Clinical and immunological studies were performed to confirm a type I hypersensitivity mechanism in a case of occupational asthma to grass pea flour exposure, used in the industrial processing of parquet. METHODS: occupational asthma was diagnosed according to patient history, PEFR monitoring and a specific bronchial challenge test. Skin prick test with an aqueous grass pea flour extract, specific IgE determinations (CAP assay) and IgE immunoblot tests were performed. RESULTS: skin prick test with the extract showed a positive immediate response, and negative response in controls. Specific IgE to grass pea was positive (9.57 KU/l). Immunoblotting demonstrated the presence of specific serum IgE that recognized 3 proteins in the extract (MW 46, 32 and 28 kDa). PEFR monitoring showed positive results. Bronchial challenge test with the extract elicited an isolated immediate response. CONCLUSIONS: as far as we know this is the first time that IgE mediated occupational asthma caused by grass pea is reported and it is also the first time that its allergens are characterized. Grass pea flour might constitute a relevant occupational allergen in this unreported source of exposure in parquet manufacturers.