STUDIES IN EXPERIMENTAL LATHYRISM. III. EFFECT OF LATHYRISM ON THE IMINO ACIDS OF CHICK EMBRYOS.
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Animals↗
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PROTEIN HISTOCHEMISTRY OF LATHYRIC PERIOSTEUM. A STUDY OF PROTEIN-BOUND SULFHYDRYL, DISULFIDE, AND AMINO GROUPS IN THE PERIOSTEUM OF NORMAL AND LATHYRIC RATS.
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Amino Acids↗
Lathyrism: a neurotoxic disease.
Lathyrism, one of the oldest neurotoxic diseases known to Man, results from excessive consumption of the chickling pea, Lathyrus sativus, and certain related species. Once prevalent throughout Europe, N. Africa, Middle East and parts of the Far East, the disease is presently restricted to India, Bangladesh and Ethiopia. Lathyrism is a form of irreversible, non-progressive spastic paraparesis associated with poorly understood degenerative changes in spinal cord. Domestic animals, notably the horse, also develop hindlimb paralysis after prolonged feeding on lathyrus fodder. Experimental animal models of lathyrism have been reported but none has been satisfactorily investigated, and concurrence between these experimental diseases and the human condition is unproven. The culpable agent in lathyrus species that precipitates paralysis also is unknown. Current attention is focused on the glutamate analog, beta-(N)-oxalyl-amino-L-alanine acid (BOAA). While this compound is present in those lathyrus species that induce spastic paraparesis and, in large doses, reportedly causes neuropathological changes similar to glutamate neurotoxicity, there is little to compare these neuropathological changes with those found in human lathyrism. Chronic primate feeding studies utilizing BOAA need to be carried out to determine whether this agent is responsible for human lathyrism. Some species of lathyrus, notably Lathyrus odoratus, are unable to induce human lathyrism but contain a compound, beta-aminopropionitrile (BAPN), that induces pathological changes in bone ("osteolathyrism") and blood vessels ("angiolathyrism") of experimental animals without damaging the nervous system. However, related compounds, dimethylaminopropionitrile (DMAPN) and beta, beta'-iminodipropionitrile (IDPN), are chronic neurotoxins in humans and animals, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acids, Diamino↗
Studies on the aetiology and pathogenesis of motor neuron diseases. 1. Lathyrism: clinical findings in established cases.
Lathyrism is a toxic disease of the motor system constantly associated with primary consumption of the seed of Lathyrus sativus (chickling or grass pea). Neurological examination was performed on 38 affected subjects drawn from four regions of the Indian subcontinent endemic for lathyrism. All showed a consistent and largely symmetric pattern of neurological deficit similar to that displayed by 5 Europeans with longstanding lathyrism now living in Israel. Hallmarks of lathyrism include a pyramidal pattern of motor weakness combined with greatly increased tone in the thigh extensors and adductors and in the gastrocnemius muscles so that the more severely affected walk on the balls of their feet with a lurching scissoring gait. Extensor plantar responses are uniformly present in such cases, and the knee and ankle tendon reflexes are exaggerated and often clonic. Hoffmann signs and exaggerated biceps and/or triceps tendon jerks are also found in the most severely affected. Sensory signs are absent, although perverse sensations in the legs are frequently reported at the onset. Walking difficulties commonly begin suddenly but may also appear subacutely or insidiously. Some individuals experience partly reversible symptoms suggestive of a diffuse CNS excitation of somatic, motor and autonomic function.
Adult↗
Lathyrism in rural northwestern Ethiopia: a highly prevalent neurotoxic disorder.
Lathyrism is a disorder of the central motor system, induced by heavy consumption of the grass-pea, Lathyrus sativus an environmentally tolerant legume containing the neurotoxic excitatory amino acid beta-N-oxalylamino-L-alanine (BOAA). A complete door-to-door resurvey of the Dembia and Fogera regions of northwestern Ethiopia, areas endemic for lathyrism, revealed an estimated mean disease prevalence of 0.6%-2.9%. Most patients developed the disease in the epidemic of 1976/77, although new cases appear to have occurred with an estimated mean annual incidence of 1.7:10,000. Production and consumption of grass-pea is increasing in Ethiopia, making attempts to develop low-BOAA strains to prevent lathyrism increasingly important.
Adolescent↗
Lathyrism: evidence for role of the neuroexcitatory aminoacid BOAA.
Lathyrism, a form of motoneuron disease induced by excessive consumption of th legume Lathyrus sativus (chickling pea), presents as signs of pyramidal tract involvement. Primate feeding studies show that beta-N-oxalylamino-L-alanine (BOAA), a potent neuroexcitatory aminoacid in the chickling pea, induces corticospinal dysfunction similar to that seen in animals consuming a fortified diet of this legume. BOAA, a potent agonist of the excitatory neurotransmitter glutamate, is likely to be causally associated with lathyrism in man.
Adolescent↗
Collagenase activity of cartilage in rats with experimental lathyrism: a model of bone diseases.
Collagenolytic activity was estimated in skin and joint cartilage of lathyritic rats by means of a biological assay. Lathyrism was induced by feeding beta-aminopropionitrile fumarate for six weeks, and the lathyritic state was confirmed by characteristic radiographic, histomorphologic and biochemical findings. Both tissues in lathyritic animals revealed significantly increased collagenolytic activity in comparison with those of the control animals. Studies were performed using ethylendiaminetetraactate and normal rat serum to determine the origin of inhibition of the collagenolytic system inhibition. Since both agents showed no inhibition of collagenolysis, the highly increased collagenolytic activity in lathyritic skin and joint cartilage appears not to be derived from polymorphonuclear cells nor from serum, but from the tissue itself. Elevation of collagenase activity may be important with respect to the increased neutral salt solubility of collagen and hydroxyproline excretion observed in experimental lathyrism.
Aminopropionitrile↗
Studies of the etiology and pathogenesis of motor neuron diseases. III. Magnetic cortical stimulation in patients with lathyrism.
Neurophysiological assessments of central motor pathways were conducted of 11 Spanish subjects with varying degrees of spastic paraparesis (lathyrism). The disease has been induced more than 40 years ago by subsistance on the neurotixic chick pea Lathyrus sativus. Patient evolution was carried out by magnetic cortical and electric spinal stimulations and recordings of the contralateral muscle responses. Central motor conduction times corresponding to lower limbs were clearly more prolonged in those severely affected patients with marked difficulty walking (Stages 4 and 3). Central conduction times corresponding to upper limbs were delayed in only 1 patient. Taken together with clinical and published neuropathological data, these findings suggest that established lathyrism is essentially a central motor system disorder primarily affecting corticospinal tracts regulating the lower limbs.
Age of Onset↗
Lathyrism in laying hens and increases in egg weight.
The cause of the increased egg weight in hens with lathyrism was investigated by feeding laying birds with diets containing beta-aminopropionitrile, the toxic principle of certain legume seeds in the genus Lathyrus. There was a significant increase (P less than 0.01) in the amount of albumen in the egg owing to an increased formation of thin white. The water permeability of the shell membranes demonstrated an increased porosity and a loss of tensile strength which contributed not only to a high water uptake but also to abnormalities of the shape of eggs during 'plumping'. It was concluded that a defect in the shell membrane protein system alters the membrane's general properties and that the increased egg weight in lathyrism is a result of the defect.
Aminopropionitrile↗
Epidemiological study of lathyrism in northwestern districts of Bangladesh.
Two northwestern districts of Bangladesh with a population of 629,752 were surveyed from June 1991 to March 1993 to detect and follow up lathyrism patients. Out of 2,567 neurological patients, 882 were diagnosed as having lathyrism, giving a prevalence rate of 14.0/10,000. This prevalence was higher among young males: only 12.9% of the patients were female, and only 19.3% of the patients were over 30 years of age at onset of the disease. The average family size was 4.6 members. In the surveyed area, 730 families were evaluated: 622 families had only 1 affected member, and 108 families had 2-8 affected members. Most of the patients were working, while only 4% were not. The majority of the patients had a very low intake of animal protein. A few cases of human T-lymphotropic virus infection and osteolathyrism were found during this study.
Adolescent↗
Lathyrism and the half-life of collagen.
Maturation of collagen in the periodontal ligament has often been designated as the cause of tooth eruption. The fact that collagen has a high turnover rate provided some sort of proof of this hypothesis. It is well known that lathyrogens decrease eruption rate. Experiments were performed, using Wistar rats, which looked into the relationship between collagen turnover and lathyrism. The collagen turnover was established in teeth not erupting after the administration of lathyrogens. These results were compared to those obtained after having stopped eruption by the placement of a goldcrown on the lower incisors. It was found that lathyrism, and therefore collagen maturation, did not influence turnover rate. Thus the supposition, that collagen is responsible for tooth eruption, becomes doubtful.
Aminoacetonitrile↗
The epidemiology of lathyrism in north and central Ethiopia.
Lathyrism is a neurotoxic disorder caused by excessive, prolonged consumption of the hardy, environmentally tolerant legume, the grass-pea, Lathyrus sativus, which contains the neurotoxic amino acid beta-N-oxalylamino-L-alanine acid (BOAA). The disease develops after heavy consumption of grass-pea for over two months. It is uniformly manifested by a predominantly motor spastic paraparesis with varying degrees of disability. A door-to-door epidemiological survey for the disease using trained lay health workers was carried out in the major areas of northwest and central Ethiopia where L. sativus is grown. For security reasons, some of the other endemic areas wre not accessible for the survey. The survey involved a population of 1,011,272. A total of 3,026 affected persons were identified. The disease was found to be widespread in the northwest and central highland areas of the country. The prevalence rates ranged from 1/10,000 to 7.5/1,000. The highest prevalences were in North and South Gonder, and East and West Gojam. The male:female ratio of cases was 2.6:1; the females exhibited a milder form of the disease. The cultivation of L. sativus is increasing in Ethiopia, which makes the development of low-BOAA strains very important in order to control the high incidence of lathyrism, a crippling disease which affects the productive young members of the society.
Adolescent↗
Peripheral nerve regeneration in primates during D-penicillamine-induced lathyrism.
We have attempted to alter collagen metabolism in young squirrel monkeys by inducing lathyrism with D-penicillamine to weaken scar tissue. We then tested the effectiveness of this drug in improving regeneration of transected peripheral nerves at the wrists using a dose of 200 mg/kg/day. We did find a significant increase (doubling) in the soluble collagen in Ivalon sponge samples that had been implanted 3 weeks after the onset of drug treatment. We also compared the control and treated groups in terms of :(1) the rate of appearance of evoked muscle action potentials, (2) the amplitude of evoked muscle action potentials, and (3) the nerve conduction velocities. Using these tests we were not able to demonstrate any improvement in the quality or rate of nerve regeneration. The possible explanations for these observations are discussed.
Action Potentials↗
Lathyrism: aortic and cutaneous collagen in the rat.
In the rat the administration of lathyrogenic toxic agents at low doses over prolonged periods of time caused simultaneous alterations in aortic and cutaneous tissues. BAPN caused an increase in soluble collagen in the skin, but in aorta there was no increase in neutral salt soluble collagen, but an increase in the amount that could be solubilized with pepsin. Type III collagen was found to represent 7% in the control aorta samples and this level was not affected by BAPN. In skin Type III accounts for 11% of the extractable collagen in controls and 14% in lathyritic animals. Biochemical changes observed in this study show evidence for collagenous lesions by increases in solubility in both skin and aorta but in neither tissue was the percentage of Type III altered by lathyrism.
Aminopropionitrile↗
Psychosocial assessment of lathyrism patients in rural Estie district of South Gondar, northern Ethiopia.
Three hundred and thirty three patients in the lathyrism endemic rural Estie district of Northern Ethiopia were interviewed and examined to assess the psychosocial impacts of neurolathyrism. The majority of the affected were in the age group of 11-20 years (43%) followed by 21-30 years (29%). Males were more affected than females (4.8:1). Peak occurrences of neurolathyrism was observed at time of mobilization of the population in villagization and land diversification schemes. Females were affected to lesser extent and at an earlier age than males. Neurolathyrism affected matrimony among the rural farming population where marriage is considered as the most significant social achievement of any young member of the society. Divorce rate due to paralysis was 28%. It also influenced the choice of occupation among the afflicted rural people. Many males went into ecclesiastical professions. A significant number of males also took up occupations which traditionally were considered to be exclusively for women like basketry and embroidery. More females, not withstanding their age, were engaged in cattle-keeping. During the study, the rural communities were made aware of the association of neurolathyrism and consumptions of grass pea seed. It is believed that this step will enable communities to use home-based detoxifying methods and resort to alternate crops during times of food shortage.
Adolescent↗
[Influence of x-rays on depolymerization of lathyric collagen fibers reconstituted in vitro].
Irradiation of native collagen from lathyric rats in solution reduces the depolymerisation speed in the cold of fibres formed by gelification at 37 degrees C, rendering it thus comparable to the speed observed with normal collagen. In our test this normalisation does not appear if the collagen is irradiated in the state of gel. These observations and the absence of specific modifications induced by irradiation in the presence of reagents of the aldehydes speak in favour of the interference, on irradiation, of chemical groups different from the physiological aldehyde groups.
Aminopropionitrile↗
Lathyrism: mini-review and a comment on the lack of effect of protease inhibitors on osteolathyrism.
Lathyrism has been reviewed in respect to four overlapping phases: finding an animal model for neurolathyrism, characterizing osteolathyrism in respect to its possible use as an animal model for human diseases, such as Marfan's syndrome, idiopathic juvenile scoliosis, etc., use of beta-aminopropionitrile (BAPN) as a tool to study collagen, and use of BAPN as a therapeutic agent in man. Because it has been suggested that the lathyrogen, BAPN, may stimulate the release of proteases, the protease inhibitors Trasylol and epsilon-aminocaproic acid (EACA) were given alone or in combination to BAPN-treated rats. The protease inhibitors did not reduce the effects of BAPN as measured by exostosis formation or collagen extractability.
Aminocaproates↗
[Chronic lathyrism. Protective effect of pyridinol carbamate on connective tissue lesions in the rat (author's transl)].
The use of lathyric toxins (BAPN) in low dosage (1 g/kg/day) for a period of 8 weeks caused in the rat simultaneous changes in the skin and aortic connective tissues. In the skin. collagen tissue was dislocated and broken in fragments, the elastic tissue disappeared, the fibroblasts were vacuolized and presented evidence of injury. These lesions were comparable to those observed in human skin during ageing. The addition of pyridinol carbamate (PDC) to BAPN prevents the formation of lesions of the elastic tissue and of fibroblasts. When given after the cessation of the lathyrogen treatment PDC arrested the formation of the lesions and accelerated their regression.
Aminopropionitrile↗