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Results for “AMINOPROPIONITRILE”

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At least 595 records · Page 33Linked to original sources
PubMed1991

Initial evaluation of developmental malformation as an end point in mixture toxicity hazard assessment for aquatic vertebrates.

The joint toxic action of three binary mixtures was determined for the embryo malformation endpoint of the aquatic FETAX (frog embryo teratogenesis assay: Xenopus) test system. Osteolathyrogenic compounds and short-chain carboxylic acids, representing separate, distinct modes of action for induction of malformation, were selected for testing in 96-hr, static-renewal tests. Three mixtures were tested for each combination, with each combination being tested on three separate occasions. Using toxic unit analysis, the combination of osteolathyrogens and the combination of carboxylic acids produced strictly additive (concentration addition) rates of malformation, while the combination of an osteolathyrogen and a carboxylic acid was less-than-additive (response addition) for induction of malformation. Therefore, developmental malformation may have value as an endpoint in mixture toxicity hazard assessment.

Abnormalities, Drug-Induced↗
PubMed1987

The variation of sonic plesio-velocity in dose dependent lathyritic rabbit femurs.

It has been hypothesized that the origin of the increased elastic modulus of mineralized bone compared with the demineralized bone matrix is in the higher crosslinking density of the collagen in bone. Osteolathyrism is ascribed to an inhibition of crosslinking of the collagen by the lathyrogen and should be accompanied by a decrease in the elastic modulus of the bone. Dose dependent osteolathyrism was induced by varying the amount of BAPN ingested per day by young New Zealand white rabbits until they were mature. The femurs exhibited dose dependent properties, including wet bone density and sonic plesio-velocity in the radial direction. It was found that there is no minimum critical dose. Even though no overt osteolathyritic stigmata could be observed, both the sonic properties and the wet bone density could be affected at any dose level. The sonic plesio-velocity and the longitudinal elastic modulus decreased with BAPN dose level, most rapidly at the lower dose levels and then less so at higher dosages. Since BAPN acts to inhibit the crosslinking density, it appears that the elastic moduli of bone are dependent on the crosslinking density.

Aminopropionitrile↗
PubMed1995

Reduced concentrations of collagen cross-links are associated with reduced strength of bone.

The known cross-links of bone collagen are derived from lysine and hydroxylysine. The first step in the enzymatic cross-linking process is a deamination by lysyl oxidase producing an aldehyde which then may condense with a lysyl or hydroxylysyl residue of a neighbouring collagen molecule. Some of the resulting divalent aldimine and oxo-imine cross-links may later on be incorporated in trivalent hydroxylysyl-pyridinoline and lysyl-pyridinoline cross-links. In bone collagen prepared from the cancellous bone of vertebral bodies of osteoporotic individuals we found a reduced stability towards acetic acid and pepsin, and a substantial reduction in the concentration of the divalent collagen cross-links compared with sex- and age-matched controls. To what extent do the collagen cross-links influence the mechanical properties of bone? beta-amino-propionitrile (BAPN) irreversibly inhibits the enzyme lysyl oxidase and therefore, the formation of cross-links between the collagen molecules. In the present study female rats, 70 days old, injected subcutaneously two times daily with BAPN (333 mg/kg/day) for 1 month and saline injected control rats were studied. The concentration of the hydroxypyridinium cross-links of femoral mid-diaphyseal cortical bone was determined by HPLC with fluorescence detection and the mechanical properties of the rat femoral diaphyses were analyzed by a materials testing machine. The BAPN injections resulted in a 45% reduction in the concentration of the hydroxypyridinium cross-links and a 31% decrease in the stability of the bone collagen towards acetic acid and pepsin compared with the control rats. No changes were found in ash or collagen concentrations of the cortical bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopropionitrile↗
PubMed1976

Observations on the mechanism of 99mTc-labeled phosphate complex uptake in metabolic bone disease.

This communication describes a series of clinical and animal in vivo and in vitro investigations designed to elucidate the mechanism of 99mTc-Sn-phosphate complex concentration in metabolic bone disease. Rachitic and lathyritic animals were used as experimental models. Based on these studies it is concluded that 99mTc alters the pharmacology of the phosphate complexes, in particular pyrophosphate, which was the test agent most extensively employed, so that the usual affinity for mineral is for the greater part replaced by organic matrix binding. There is also evidence to suggest the immature collagen moiety of the organic matrix is the prime target of 99mTc-Sn-phosphate complex binding. Specifically, the aldehyde groups of the collagen molecule are suspected as being the major site of interaction.

Aminopropionitrile↗
PubMed2000

Intra- and extracellular enzymes of collagen biosynthesis as biological and chemical targets in the control of fibrosis.

The several steps in the pathway for the biosynthesis of fibrillar collagen are reviewed to illustrate potential sites for the chemotherapeutic control of fibrosis. Particular emphasis is placed upon the properties and inhibition of lysyl oxidase, the enzyme which initiates the covalent crosslinking of extracellular collagen molecules converting these to insoluble fibers, and upon the properties and inhibition of prolyl hydroxylase, the intracellular enzyme which hyroxylates proline residues within collagen.

Aminopropionitrile↗
PubMed1997

Micro-injection of recombinant lysyl oxidase blocks oncogenic p21-Ha-Ras and progesterone effects on Xenopus laevis oocyte maturation.

Previous evidence suggested an anti-oncogenic role for lysyl oxidase, mainly in ras-transformed cells. Here we prove that recombinant lysyl oxidase is actually able to antagonize p21-Ha-Ras-induced Xenopus laevis oocyte maturation. Lysyl oxidase was also effective on progesterone-dependent maturation, indicating a block lying downstream of Ras. Maturation induced by activated 'maturation promoting factor', normally triggered by progesterone, was also inhibited by lysyl oxidase. Finally, lysyl oxidase did not abolish p42Erk2 phosphorylation upon maturation triggering, suggesting a block downstream of Erk2. Further investigation showed that lysyl oxidase action depends on protein synthesis and is therefore probably mediated by a newly synthesized protein.

Aminopropionitrile↗