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Acute urinary bladder toxicity of a polyurethane foam catalyst mixture: a possible new target organ for propionitrile derivative.

The toxicity of the mixture NIAX-ESN which contains 95% dimethylaminopropionitrile was evaluated in male rats. Large doses (2.0 ml/kg ip) rapidly produced CNS excitation followed by depression and death. The mixture (given orally as two doses of 0.31 or 0.62 ml/kg respectively) induced acute urinary bladder lesions in 3 days. The changes consisted of massive transmural edema, acute ulcers and inflammation and, occassionally hemorrhagic necrosis of the bladder wall.

Aminopropionitrile↗

[Chronic lathyrism, prolonged hyperlipidic diet, and atheroma in the rat].

Deep, constant, extensive atherosclerosis can be experimentally induced on rats that are atheroresistant. Two main factors are involved in this experimentation; parietal alteration following chronic intoxication with BAPN (9 weeks) and a metabolic factor with hyperlipidic diet, but this metabolic damage should be sustained for a long time (40 weeks).

Aminopropionitrile↗

Galactosyl transferase assay. Application to experimental atherosclerosis.

To establish a repetitive measurement, aortic galactosyl transferase activity has been studied with a specific exogenous acceptor, collagen. Reactions were realized with an acellular biosynthesis mixture containing, collagen (3-4 mg/ml) an aliquot of enzymatic extract preparation (105000 g supernatant (2-3 mg/ml of proteins), UDP (14C) galactose (300 pM/ml). Galactose incorporation into collagen required Mn++ (2.5. 10-3M), incubation temperature of 37 degrees C and pH =7,75. Under such conditions a reproducible assay of aortic collagen galactosyl transferase was possible. After submitting rabbits to a chronic lathyric intoxication and/or to an hypercholesterolimic diet, galactosyl transferase activity was measured in rabbit aortic wall. Enzymatic activity was increased for rabbits under treatment, and the increase was directly proportional to the length of treatment (BAPN associated with cholesterolemic diet).

Aminopropionitrile↗

Collagen responsible for tooth eruption? A study of the eruption of rat incisors.

The rate of turnover of collagen in periodontal ligament (PDL) is closely associated with the process of tooth eruption and tissue adaptation allowing good anchorage of the tooth within the socket. Collagen may even be associated with orthodontic relapse. As the collagen protein seems to play a key role in tooth eruption, the investigation concentrated on the presence and maturation of collagen and its possible function in the process of tooth eruption.

Aminoacetonitrile↗

Morphologic aspects of experimental esophageal lye strictures. II. Effect of steroid hormones, bougienage, and induced lathyrism on acute lye burns.

Among 77 dogs surviving standardized transmural esophageal lye injury for at least 2 weeks and as long as 12 weeks, 24 were untreated, 26 received corticosteroids and bougienage (S&B), and 27 received only the lathyrogen beta-aminoproprionitrile (BAPN). Stricture frequency was reduced markedly and significantly in the S&B and BAPN groups when compared to the controls (p less than 0,01). Strictures resulted from inward circumferential remodeling of all mural layers, not proliferating bulky scar tissue, and persistent ulceration was apparently not an influential factor in any group. The S&B dogs invariably showed reduction of the internal or mucosal length of the injured segment as compared to the outer length; these relations were quite variable in the other two groups so that mean internal shortening was significantly greater (p less than 0.01) in the S&B group. Marked mural thinning in the injured zone was present in all three groups but was most frequent in the BAPN-treated animals. The major conclusion is that BAPN-induced changes in the physical properties of reparative tissue can increase the ultimate caliber of an injured hollow viscus without resort to mechanical bougienage. In addition, the data suggest that wound contraction may play a role in stricture formation in this model.

Adrenal Cortex Hormones↗

[Effect of benzquercin on the connective tissue of lathyritic mice. Optic and electron microscopic study].

Vascular pathology is characterized by important alterations of some vessel macromolecular constituents, such as fibrous proteins, collagens and elastin. The purpose of our study was to establish the activity of benzquercin treatment on such alterations of the vascular wall. As experimental model we used lathyrism induced in mice by chronic administration of beta-amino-propionitril (beta-APN). This compound prevents crosslink-formation in elastin and collagen and provokes a disorganization of the structure and an alteration of the physiological functions of the vascular wall. The connective tissue of the skin is also impaired simultaneously with that of the blood vessels. We compared by optical and transmission electron microscopy the morphological structure of the aorta and the skin of 3 groups of mice: a normal control group, an other which only received the beta-APN alone and a third one which received the beta-APN and the benzquercin treatment. The second group, injected with beta-APN without treatment, showed important alterations of the structure of the aorta as well as of the skin. Both fibrous proteins, collagen and elastin were concerned by these alterations, the consequence of which was an increase of the permeability of the aorta wall demonstrated with the horse-radish peroxydase as a tracer. The third group, injected with beta-APN and treated with the benzquercin, showed much less morphological disorders than the untreated group and the vascular permeability was also close to normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopropionitrile↗

The marfan's syndrome. In vitro study of collagen metabolism in tissue specimens of the aorta.

Tissue specimen of the aorta was obtained from a patient with Marfan's syndrome after heart surgery. Media and adventitia were carefully separated and subsequently used for biochemical characterization. Aortas from an embryonic calf and from a human adult were used as internal controls. The data clearly indicated that an insufficient synthesis of type I collagen rather than a defect in the formation of cross-links may be the prime cause in this inherited connective tissue disorder. Such a disturbance in the regulation of the genes coding for the different collagen chains may explain the weakness and enhanced extensibility of the blood vessels finally resulting in an aneurysm.

Aminopropionitrile↗

Teratological studies on craniofacial malformations.

Craniofacial malformations cause great human suffering. The purpose of the experimental studies was to investigate teratogenically induced craniofacial malformations in the rat, and to study if vitamin B6 could prevent the teratogenically induced malformations in the rat. The aim of the clinical investigation was to compare mandibulofacial dysostosis (MFD) with hemifacial microsomia (HFM) and thalidomide-induced malformations restricted to the first and second branchial arches. In the experimental studies we used two different teratogenic agents, etretinate and BAPN (beta-aminoproprionitrile). Vitamin B6 was administered one day prior to and simultaneously with the teratogenic agent. The induced malformations were observed by direct microscopy, histology, differential staining, microdissection and enzyme histochemistry. Knowledge of isoenzymic differentiation was obtained by isoelectric focusing and polyacrylamide gel electrophoresis. The clinical features of 29 patients with MFD, 26 with HFM and seven with thalidomide-induced malformations were investigated. The patients underwent clinical investigations, radiography, tomography, computed tomography, surgical exploration and audiograms. The etretinate-induced syndrome in the rat shows similarities to first and second branchial arch syndromes in man. Defective formation of Meckel's cartilage and the cartilaginous skull base, the zygoma and the middle ear ossicles were prominent features of the observed malformations. The induced malformations were accompanied by increased staining for alkaline phosphatase (APase) in the skull and skull base cartilages and Meckel's cartilage. BAPN induced cleft palate in 95% of the cases and the teratogenically induced cleft palate was accompanied by a pathological differentiation pattern that could be traced by determination of isoenzymes in the palatal shelves as well as in amniotic fluid. Vitamin B6 could prevent the teratogenic malformations induced by etretinate and BAPN in the rat. Comparing MFD, HFM and thalidomide-induced malformations, all syndromes included patients with external, middle and inner ear malformations. Cranial nerve palsy/paresis was only seen in HFM and thalidomide-induced malformations. A relationship between disturbed neural crest cell migration and defects of the first and second branchial arches seems possible.

Alkaline Phosphatase↗

Collagen cross-linking. Synthesis of collagen cross-links in vitro with highly purified lysyl oxidase.

In this paper, the synthesis of collagen cross-links in vitro was investigated in a defined system consisting of highly purified chick cartilage lysyl oxidase and chick bone collagen fibrils. Cross-link synthesis in vitro was quite similar to the biosynthesis of collagen cross-links in vivo. Enzyme-dependent synthesis of cross-link intermediates and cross-linked collagen derived from lathyritic collagen occurred. The concentration of the two principal reducible cross-links, N6:6'-dehydro-5,5'-dihydroxylysinonorleucine and N6:6'-dehydro-5-hydroxylysinonorleucine, increased to a peak value of approximately two cross-links per molecule and then decreased. Synthesis of histidinohydroxymerodesmosine and a second polyfunctional cross-link of unknown structure began after synthesis of bifunctional cross-links was largely completed and proceeded linearly afterwards. Inhibition of lysyl oxidase after the bulk of bifunctional cross-link synthesis had occurred did not alter the rate of decrease in reducible cross-link concentration but did inhibit further histidinohydroxymerodesmosine synthesis. These results indicate that lysyl oxidase and collagen fibrils are the only macromolecules required for cross-link biosynthesis in vivo. It is likely that the decrease in reducible cross-links observed during fibril maturation results from spontaneous reactions within the collagen fibril rather than additional enzymatic reactions.

Amino Acid Oxidoreductases↗