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Collagen-affecting drugs impair regeneration of teleost tail fins.

Regenerating tail fins were studied in two species of teleosts, Tilapia rendalli and Cyprinus carpio, treated with indomethacin, aspirin, dexamethasone, penicillamine, and beta-aminoproprionitrile, drugs known to disrupt collagen metabolism in mammals. Collagen was studied under the light microscope by the Picrosirius-polarization method and also under the electron microscope. In general, these drugs disturbed the deposition and organization of collagen fibrils leading to abnormally thin or practically absent lepidotrichia and actinotrichia, and also to disorganized fibrous connective tissue. The resulting disorganization of the collagenous scaffolding of the regenerating dermoskeleton was probably responsible for a secondary effect on blastema distalization and on the general fin ray patterning that were also observed. The foregoing observations suggest that the stromal histoarchitecture of the regenerate plays a vital role in fin regeneration and indicate that these drugs may be useful in studying the extracellular matrix-cell interactions at the cellular and molecular level. In addition, the present findings provide a basis for developing different biological models by using teleost fin regeneration.

Aminopropionitrile↗

Growth of a plasma cell myeloma in lathyritic mice.

Growth of a plasma cell myeloma (Adj PC-5) was studied in mice made lathyritic by the administration of beta-amino-proprionitrile (BAPN). The number of bones that had their medually cavities filled with tumor cells was notably decreased compared with tumor-bearing mice not treated with BAPN. Other aspects of tumor growth were the same. BAPN caused some retardation of tumor growth in the medullary cavity, but also caused osteoporosis and decreased tensile strength of collagen that allowed expansion of tumor growth outside the bones to proceed as usual. Additionally, the tumor-bearing mice showed some inhibition in their response to BAPN. This agrees with previous work that has shown that the response to BAPN treatment is greatest in animals that otherwise are healthiest.

Aminopropionitrile↗

[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].

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.

Aminopropionitrile↗

The effect of beta aminoproprionitrile (BAPN) on experimental amyloidosis.

Experimental amyloidosis was induced in mice with repeated injections of complete Freund's adjuvant (CFA) reinforced with bacterial vaccine. BAPN administered in a mixture with CFA or on its own before the injection of CFA reduced the incidence of amyloidosis. The reduction in the incidence of amyloidosis following the administration of BAPN may be due to its inhibitory effect on the oxidative deamination of amino acids, which presumably inhibit cross-linking of amyloid fibrils or interfere with metabolic pathways which involve the formations of mucopolysaccharide formation. It is suggested that the defective formation of the mucopolysaccharide-amyloid protein complex inhibits amyloid deposition and induces the activity of beta glucuronidase observed in the present study. The reduced incidence of amyloidosis following BAPN adminsitration cannot be due to lysosomal enzyme degradation of the amyloid as the activity of cathepsin D and acid phosphatase is decreased during this process.

Acid Phosphatase↗

[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↗

Lathyritic activity of isoniazid.

Although isoniazid is mainly known and used for its antituberculous properties, it is also a lathyrogenic agent. This paper presents data confirming the lathyritic activity of isoniazid in vitro and in vivo and suggests that its action on connective tissue may be partly responsible for its therapeutic effectiveness.

Aminopropionitrile↗

[Influence of a lathyric agent and of hypercholesterolemic serum on cell cultures of fetal rabbit aorta].

Cell cultures of foetal rabbit aorta are cultivated with a lathyric agent (beta-amino-propio-nitrile) or with an hypercholesterolemic serum; if morphological features, in these two cases, correspond with modifications observed, in vivo, when adult rabbits are respectively submitted to the same treatment, enzymatic activities of collagen metabolism vary in opposite way. Therefore, the influence of different parameters to be studied on vascular cell functions become easier.

Aminopropionitrile↗

Unusual occupational toxins.

Occupational and environmental medicine affords encounters with many unusual toxins, ranging from exotic metals to rocket fuels. Twelve of the most unusual industrial toxins are reviewed here and their clinical manifestations and treatments explored: acetonitrile, acrylonitrile, boron hydrides, dimethylaminopropionitrile, dimethylformamide, hydrazines, methyl isocyanate, 2-nitropropane, phosphine, Stalinon, tellurium, and vanadium.

Acetonitriles↗

[Enzyme alterations of the arterial wall following the combination of a lathyrogenic treatment and of moderate hypercholesterolemia in the young rabbit].

To determinate the part of humoural and parietal factors in atherosclerotic injury genesis, metabolism alteration study is realised on aortic cell wall of rabbits which are submitted to a chronical lathyritic intoxication alone, or simultaneously or alternatively associated with a cholesterolemic diet. Catabolic activity increase of beta-glucuronidase occurs in hypercholesterolemic rabbits. Beta-aminoproprionitrile, lathyrogenic drug used, stimulates biosynthetic pathways: increase of soluble proteins, energetic enzyme activities (lacticodeshydrogenase, malicodeshydrogenase), conjonctival protein metabolism (procollagen lysyl hydroxylase); in the same time, cell wall disturbances and lipidic deposits are facilitate when rabbits are submitted to cholesterolemic diet.

Aminopropionitrile↗

Quantitative analysis of inflammatory cell influx, procollagen type I synthesis, and collagen cross-linking in incisional wounds: influence of PDGF-BB and TGF-beta 1 therapy.

Platelet-derived growth factor (PDGF-BB homodimer) and transforming growth factor-beta 1 (TGF-beta 1) are potent wound-healing hormones that accelerate incisional repair. To identify more precisely and quantitatively the stage(s) of wound healing influenced by growth-factor therapy, we investigated the three sequential tissue repair processes--inflammatory cell influx, intracellular procollagen type I (PC-I) synthesis, and collagen cross-linking--in recombinant growth factor--treated wounds. Using newly developed automated, quantitative image-analysis techniques, we observed that PDGF-BB markedly augmented the directed migration of macrophages into wounds during the first week after wounding and triggered and earlier and more sustained influx of PC-I--containing fibroblasts into the wound when compared with results in TGF-beta 1-treated or control wounds (p = 0.015 at day 2; p = 0.007 at day 21). In contrast, automated image analysis revealed TGF-beta 1-treated wound fibroblasts had a nearly twofold increase in intracellular levels of PC-I protein when compared with PDGF-BB-treated or control wound fibroblasts (p = 0.004 at day 4). However, the influence of TGF-beta 1 was transient, and the longer duration of PDGF-BB activity suggested a later influence, perhaps on the collagen remodeling phase, which is ultimately required for increased wound strength. To address this possibility, collagen cross-linking in growth factor-treated wounds was inhibited by beta-aminoproprionitrile (BAPN) treatment, and wound breaking strength was analyzed. Both PDGF-BB and TGF-beta 1 continued to enhance repair in BAPN-treated rats, indicating that they do not function primarily at the level of collagen cross-linking. Thus, PDGF-BB appears to enhance the inflammatory phase of wound healing to indirectly trigger PC-I synthesis, whereas TGF-beta 1 quantitatively enhances PC-I synthesis directly, accounting for their differing duration of activities within healing wounds.

Aminopropionitrile↗

Experimental myopia in tree shrews.

When deprived of form vision during postnatal development, tree shrews reliably develop an axial myopia characterized by elongation of the vitreous chamber, zonular dysplasia and a slight reduction in lens weight and thickness. Corneal flattening has been observed in animals visually deprived by eyelid suture but is absent in animals visually deprived with an opaque goggle. The sensitive period for myopia development starts about 15 days after the eyes open and sensitivity remains high for about 3-4 weeks thereafter. Recovery from experimental myopia can occur in tree shrews that are visually deprived using goggles for a short period. Blockade of action potentials from ganglion cells in deprived eyes by intravitreal injections of tetrodotoxin (TTX) does not prevent the development of myopia, suggesting that local retinoscleral mechanisms can contribute to experimental myopia in this species. Open eyes receiving intravitreal injections of either saline or TTX have shorter vitreous chambers than control eyes, suggesting that puncturing the globe reduces forces within the eye that contribute to its expansion. Animals treated intraperitoneally with lathyritic agents to block collagen cross-linking for three weeks during a 75-day period of monocular visual deprivation develop a very large myopia in the visually deprived eye that is accompanied by a large vitreous chamber elongation and marked thinning of the posterior sclera. The results from studies in tree shrews are consistent with the suggestion that an internally driven expansion acts in concert with ocular growth to increase the axial length of the eye, helping to move the eye from hyperopia toward emmetropia. The resistance of the sclera and/or choroid to this expansion may be affected by activity within the retina. Increased retinal activity associated with achieving a clear image on the retina may result in increased resistance to expansion, helping to hold the retina at the focal plane. Recovery may occur by a slowing of axial expansion while the optical surfaces proceed toward adult values.

Aminopropionitrile↗

Effect of (+)catechin on connective tissue.

The effect of (+)catechin on connective tissue was studied in organ cultures of chick embryo tibiae and after in vivo injection in rats and mice. Collagen biosynthesis and hydroxylation of 14C-Pro-labelled protocollagen in vitro by protocollagen proline hydroxylase (PPH) were inhibited. In vivo, a slight decrease in the biosynthesis of collagen and in the PPH activity in skin of rats and mice was noticed as an effect of (+)catechin. No effect of the drug was observed on the incorporation of 14C-D-glucosamine by chick embryo tibiae. Increased urinary excretion of acid mucopolysaccharide metabolites by the mice injected with (+)catechin was observed.

Aminopropionitrile↗

The role of neutrophils in the development of cadmium chloride-induced emphysema in lathyrogen-fed hamsters.

This study was designed to evaluate the role of neutrophils (PMNs) in the pathogenesis of emphysema. After administration of CdCl2 intratracheally to hamsters fed a lathyrogen, beta-amino propionitrile fumarate (BAPN), the classic lesions of emphysema developed. Administration of specific antineutrophil serum markedly reduced the PMN influx into the lungs which followed CdCl2 exposure and produced a substantial decrease in elastase and collagenase content of bronchoalveolar lavage fluid (BAL). The degree of emphysema in PMN-depleted hamsters given BAPN and CdCl2 was not different from that in hamsters given BAPN and CdCl2. Furthermore, the degree of acute lung injury following CdCl2, as determined by hydroxyproline content of BAL and by lung lipid peroxidation, was the same in PMN-depleted and non-depleted groups. Thus, PMNs were not necessary for the induction of emphysema in BAPN-CdCl2-treated hamsters. The results suggest that PMNs may not be obligate mediators of emphysema.

Aminopropionitrile↗

[The biochemistry of collagen and the locomotor apparatus. Hereditary diseases of connective tissue and rheumatologic diseases (part 2)].

In lathyrism, the toxic agent directly blocks the development of the transverse links in the collagen fibre, while in bovine dermatosparaxis there is a deficiency of procollagen peptidase. Of the many clinical forms of the Ehlers-Danlos syndrome, some are due to a deficiency of lysine oxidase, others to deficiency of lysine hydroxylase and still others to procollagen peptidase deficiency. The essential deficiency in Marfan's disease is still unknown, but that in homocystinuria causes blocking of the groups necessary to form the transverse links. In osteogenesis imperfecta, which is probably a heterogeneous group, there is deficient consolidation of the collagen fibrils, the cause of which is still unknown. One possibility is a quantitative imbalance between chains of different types. In scleroderma there is excessive synthesis of an apparently normal connective tissue; the cause of this is also still unknown.

Aminopropionitrile↗