New findings and symptomatic treatment for neurolathyrism, a motor neuron disease occurring in north west Bangladesh.

Neurolathyrism is a form of spastic paraparesis caused by the neuroexcitatory amino acid 3-N-oxalyl-L-2,3-diaminopropanoic acid (beta-ODAP) present in the seeds and foliage of Lathyrus sativus. The disease is irreversible and usually nonprogressive. Tolperisone HCl, a centrally acting muscle relaxant, has been shown to reduce significantly the spasticity in neurolathyrism patients. Sporadic occurrence of HTLV-1 infection (0.9%) and of osteolathyrism was found among the neurolathyrism patients. Osteolathyrism is linked to the consumption of the green shoots of Lathyrus sativus.

Effect of lathyrogen on collagen of methylcholanthrene-induced sarcoma of rat.

Since the lathyrogen beta-aminopropionitrile is known to affect the fibrogenic and physical properties of collagen polymers, we have examined its effects on collagenous components of methylcholanthrene-induced fibrosarcoma in rat. Lathyrogen treatment reduced total collagen content of tumours from approximately 17 to 12 mg collagen/g tissue. It also proportionately increased the solubility of specific collagen fractions, the summation of all extractable solubilized collagens reflecting 37 and 67% of total collagen content for control and lathyric tumours, respectively. Although lathyrogen had no significant effect on the growth and overall size of fibrosarcoma, histological studies confirmed that changes had occurred to appearance and distribution of collagenous components of extracellular matrix.

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.

[Effect of pyridinol carbamate on long-term lathyrism and experimental atheroma in the rat. Histological and biochemical study]. / Action du pyridinol carbamate sur le lathyrisme au long cours et l'athérome expérimental chez le rat. Etude histologique et biochimique.

Three-week-old rats were fed with Beta-aminopropionitrile (BAPN) with a normal or hyperlipidic diet. After a few weeks BAPN induced aortic elastic fibres disruption which as not worsened when the treatment was continued up the seven months. Adding a hyperlipidic diet produced atherosclerotic-like lesions. Pretreatment with Pyridinol Carbamate (PDC) whichever the diet used did not modify serum of aortic cholesterol levels. It decreased the severity of aortic lesions and delayed the onset of less severe atheromatous lesions. It seems that PDC increased the free/esterified aortic cholesterol ratio resulting in a better elimination of the aortic cholesterol.

Pharmacological study of a new non-steroidal anti-inflammatory drug: protacine (CR 604).

The pharmacological activities of 3'-(4-[2-(1-p-chlorobenzoyl-5-methoxy-2-methyl-indol-3-yl-acetoxy)-ethyl]-piperazin-1-yl)propyl-4-benzamido-N,N-dipropylglutaramate(+/-)dimaleate (protacine, CR 604), a new indolyl derivative with strong anti-inflammatory, analgesic and antipyretic activities, are described. The dose-dependent activity of protacine on inflammation has been shown both in short-term experiments, like the hind paw edema induced by carrageenin and several other irritants, and long-term tests, like the aminoacetonitrile-induced osteolathyrism, the adjuvant-induced arthritis and the cotton pellet-induced granuloma. The analgesic activity of the drug has been evidenced in the phenylquinone-induced writhing and the Randall-Selitto tests, and the antipyretic effects in the yeast-induced hyperthermia in rats. Other general pharmacological effects have been studied, too. Contrarily to several other anti-inflammatory drugs, including indometacin, showing advers effects at doses which are in the same range of those active on experimental inflammation, protacine shows these effects to a minor degree and at doses which are much larger than those pharmacologically active. The therapeutic index of protacine therefore is superior to that of other anti-inflammatory drugs.

[Incorporation of 32P-orthophosphate in aortic phospholipids in chronic lathyrims in the rat]. / Incorporation de 32P-orthophosphate dans les phospholipides aortiques au cours du lathyrisme chronique chez le rat

Study of 32P orthophosphate incorporation into rat aortic phospholipids after B.A.P.N. treatment, which was followed or not by a lipid-supplemented diet (4.5 p. 100 cholesterol and 37 p. 100 butter). The 32P orthophosphate turnover in the total phospholipid was twice as slow among B.A.P.N.-treated rat than among control-rat. Such a decrease of the 32P orthophosphate turnover could be found as well in phosphatidylethanolamines, phosphatidylcholines and lysophosphatidylcholines. Sphingomyelins showed a very weak metabolic activity among two groups of rats. 32P orthophosphate incorporation into inositolphosphatides was slowed down by B.A.P.N. treatment. Maximal specific activity of inositolphosphatides after injection of 32P orthophosphate was reached within 4 hours in control rats, and 8 hours in B.A.P.N.-treated rats. Three months after the end of B.A.P.N. treatment, no difference in specific activity could be found between control-rats and B.A.P.N.-treated rats. Lipid supplemented diet modified the metabolic activity of phospholipids equally in control rats and B.A.P.N.-treated rats. Specific activity decrease in total phospholipids, phosphatidylcholines, phosphatidylethanolamines, and increase in lysophosphatidylcholines were noted in both groups of animals under a high rat diet. These modifications of the metabolic activity of different phospholipids were most marked fourteen hours after 32P orthophosphate injection. B.A.P.N. treatment only slowed the incorporation of 32P phosphate into phospholipids. Administration of a single lipid supplemented diet or a diet associated with B.A.P.N. treatment induced a slower turnover of phosphatidylcholines and phosphatidylethanolamines, and a faster turnover of lysophosphatidylcholines.

[LDH- and MDH-isoenzymes in the costo-chondral junction in experimental lathyrismus and under additional medication with 6-methyl-prednisolone and O-(beta-hydroxyethyl)-rutosides]. / LDH- und MDH-Isoenzyme in der Knorpel-Knochengrenze der Rippen beim experimentellen Lathyrismus und unter zusätzlicher Medikation von 6-Methyl-Prednisolon und O-(beta-Hydroxyaethyl)-Rutosiden

Several classic studies suggest that experimental lathyrism is not only based on an extracellular distrubance of collagen fibre maturation but on a disturbed cellular energy metabolism. To exemplity this in assessment of skeletal damage the isoenzymes of LDH and MDH on the bone metabolism have been determined. Thus in experimental lathyrism the capacity for glycolysis and for oxidative energy production are significantly diminished in the rib bones and rib cartilage. The resulting reduction of glycoseaminoglycans in the ground substance, thus disturbing the function of the matrix in the formation of collagen fibres. In the bone the lack of mature collagen fibres leads to a mineralisation disturbance because of impaired nucleation function. Thus experimental lathyrism cannot be regarded as a disturbed extracellular collagen metabolism. "Venoruton" could not correct the lathyrogenic disturbance of energy metabolism, but after 3 weeks 6-methyl-prednisolone caused a normalisation of the state of energy metabolism.