Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:151-18-8 (BAPN)
 130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tropoelastin, which is secreted from the cell in a soluble form, contains specific alanine rich repeat domains that are destined to form covalent desmosine and isodesmosine crosslinks in mature insoluble elastin. We raised a monospecific polyclonal antibody to a AKAAAKAAAKA synthetic peptide (AKA) which represents this alanine rich region of tropoelastin. The antibody was reactive with the original peptide antigen and purified tropoelastin, but not with mature crosslinked elastin isolated from several animal species. Conditioned media from chick aorta smooth muscle cells in culture reacted in an ELISA with the AKA antibody, but only in the presence of BAPN to block the conversion of the epsilon-amino groups to aldehydes. Immunofluorescence demonstrated that the AKA antibody decorated newly deposited tropoelastin assembled in fine fibrils in matrix produced by cultured human skin fibroblasts. EM-immunogold specifically localized this antibody to the immature elastic fibers present in fetal sheep ductus arteriosus. Moreover, immunohistochemistry demonstrated that the antibody recognized nonpolymerized tropoelastin assembled on the periphery of elastic fibers in the aorta of chicks raised on copper deficient and BAPN containing diets. These studies demonstrate that this new anti-tropoelastin antibody can be used as a useful tool to investigate elastin metabolism where it is important to distinguish between tropoelastin and mature crosslinked elastin.
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PMID:Antibody raised to AKAAAKAAAKA sequence on tropoelastin recognizes tropoelastin but not mature crosslinked elastin: A new tool in metabolic and structural studies of elastogenesis. 1075 15

The forces produced during stretches of passive and activated muscles, and isometric force deficits after stretching of activated muscles were examined in rat plantor flexor muscle-tendon complexes with reduced collagen cross-links (pyridinoline). Female Sprague-Dawley rats (n = 6, age 87 days) were injected twice daily for 43 days with beta-aminopropionitrile (BAPN, 333 mg/kg/day i.p.), an inhibitor of lysyl oxidase, which is responsible for the production of collagen cross-links. The relative weights of the plantar flexor muscles were similar for BAPN and saline-injected (control, C) rats (n = 6). Pyridinoline was lower in the tendon (22.9%), and in the plantaris (17.1%), and soleus (7.4%) muscles (P < 0.05), with no changes observed in collagen content (hydroxyproline), as determined by high-pressure liquid chromatography. At an ankle position of 90 degrees, groups had similar forces at 5, 10, 20, 40, 60 and 80 Hz before stretching. Forces at 40 degrees with stretches of the passive muscles (five times from 90 degrees to 40 degrees) were lower for all stretches in BAPN-injected rats (P < 0.05). Isometric force deficits resulting from stretches of activated muscles (80 Hz, 20 times from 90 degrees to 40 degrees, rest intervals 3 min) followed similar courses for BAPN-injected and C rats, and were 51.1 (2.4)% (C) and 54.7 (4.6)% (BAPN) before the last stretch. After 1 h of rest, isometric force deficits were 26% and 29% larger at 10 Hz and 5 Hz, respectively, in BAPN-treated rats (P < 0.05). The reduction in BAPN-injected collagen cross-linking of the skeletal muscle-tendon complex reduced the forces produced during stretches without muscle stimulation (i.e. passive stretch), and stretching of activated muscles produced larger isometric force deficits only at low stimulation frequencies.
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PMID:Force deficits after stretches of activated rat muscle-tendon complex with reduced collagen cross-linking. 1160 8

Lysyl oxidase, an extracellular amine oxidase, controls the maturation of collagen and elastin. We examined the regulation of lysyl oxidase mRNA in cultured rabbit retinal pigment epithelium (RPE) cells in relation to the changes in subretinal fluid transport and phenotype of RPE cells. The level of the mRNA in cells grown on microporous membranes was markedly increased by application of hyperosmotic mannitol solution on the apical side (191% of control), implying that RPE cells express more lysyl oxidase in the condition which may cause the accumulation of subretinal fluid. Platelet-derived growth factor increased the mRNA level in subconfluent cells in culture (137% of control) and basic fibroblast growth factor decreased it (79% of control). In addition, exposure of cells to retinoic acid alone or in combination with dibutyryl cAMP for 22 days markedly decreased the level of lysyl oxidase mRNA (52 or 35% of control) while increasing the level of mRNA of N-acetylglucosaminidase (NAG), a marker enzyme for lysosomes (162 or 142% of control). Moreover, the level of lysyl oxidase mRNA in cells grown on microporous membranes was lower than that in cells grown on plastic dishes, while the level of NAG mRNA in the former cells was higher than that in the latter. Taken together, the expression of lysyl oxidase seemed to increase during proliferation of RPE cells and decrease toward differentiation. beta-Aminopropionitrile, an inhibitor of lysyl oxidase, significantly inhibited the contraction of collagen gels by fetal calf serum, suggesting that lysyl oxidase may be involved in pathogenesis caused by RPE cells.
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PMID:Regulation of the expression of lysyl oxidase mRNA in cultured rabbit retinal pigment epithelium cells. 1212 71

Three groups of male Wistar rats received daily subcutaneous injections of 10 mg/kg of hydrocortisone (HC group), 300 mg/kg of beta-aminopropionitrile (BAPN group), or saline (control group), for 10 days. The shear stress-strain and stress-relaxation properties of the incisor periodontal ligament were examined in transverse sections from dissected mandibles. Both the maximum shear stress and failure strain energy density increased significantly following the administration of hydrocortisone. The maximum shear stress decreased following the administration of BAPN. However, the stress-relaxations in the initial 10 min did not show significant differences among the three groups. Polarized light microscopic analysis revealed that the retardation value of the collagen fibers was highest in the HC group and lowest in the BAPN group for the bone-related area, but not for the tooth-related and middle areas of the ligament. It is suggested that the changes induced by hydrocortisone or BAPN occurred mainly in the elastic components and to a minor extent in the viscous components although the physical and biomechanical properties are determined by the interaction of all the various components. We also suggest that the main response to the drugs occurred in the collagen fibers in the bone-related area of the ligament.
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PMID:Effects of hydrocortisone and beta-aminopropionitrile on stress-strain and stress-relaxation behaviors, and birefringent retardation of collagen fibers in the rat incisor periodontal ligament. 1268 64

This work is a trial to evaluate the effect of the combination of the anthelmintic drug praziquantel (CAS 55268-74-1, PZQ, EMBAY 8440, Biltricide) with the antifibrotic agent beta-aminopropionitrile-monofumarate salt (BAPN, CAS 2079-89-2). It is also a trial to elucidate the repercussions of this drug combination upon worm and tissue egg loads and oogram pattern. Moreover, it aims to study their effects on the hepatic granuloma size and the resistance to reinfection in experimental murine schistosomiasis mansoni. A group of 120 Swiss albino mice was used. This group was further subdivided into six small subgroups. Subgroup I comprised infected untreated control mice. Subgroup II comprised infected untreated challenged control mice. Subgroup III comprised challenged control mice. Subgroup IV comprised infected mice treated with PZQ 500 mg/kg b. w. orally for two successive days. Subgroup V comprised infected mice given BAPN daily as 5 mg powder in 0.5 ml saline for 14 successive days. Subgroup VI comprised mice given both PZQ + BAPN. Animals were sacrificed 12 weeks post primary infection. Mice given the combination regimen PZQ + BAPN, compared to those given each drug solely, revealed absence of worm recovery at perfusion and only dead ova in the oogram (99.2 + 0.6). Inspite of the marked reduction in the hepatic and intestinal tissue egg loads recorded, this drug combination revealed the highest score of percent resistance to reinfection (91.2 + 0.5%). The data were less salient in mice given PZQ or BAPN alone.
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PMID:Treatment of acute schistosomiasis mansoni with praziquantel and an antifibrotic agent in mice. Maintenance of resistance to infection. 1287 15

Chick embryos were sacrificed at intervals after simultaneous injection of BAPN and proline-C(14), the collagen separated into neutral salt-extractable and residue fractions, and total hydroxyproline and hydroxyproline specific radioactivity determined in each fraction. Extractable collagen, measured as hydroxyproline, increased markedly and had a higher specific activity in BAPN-treated embryos than in corresponding controls. Hydroxyproline of the residue collagen in the treated animals, however, had a lower specific activity. When proline-C(14) was injected 24 hours prior to BAPN, the specific radioactivity of the soluble collagen of treated embryos was similar to that of controls, in spite of the fact that the specific activity of the residue fraction was higher than that of the soluble fraction at the time of BAPN administration. These results suggest that the increased amount of soluble collagen in lathyrism induced by administration of BAPN does not arise from the collagen insoluble prior to administration of the drug, but rather that BAPN acts by blocking the formation of mature collagen fibers, perhaps by preventing the formation of cross-linkages between alpha-collagen chains.
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PMID:Collagen metabolism in osteolathyrism in chick embryos: site of action of beta-amino-propionitrile. 1391 38

Six weanling rats were fed a diet containing 0.4 per cent BAPN fumarate and sacrificed after 5 to 33 days on the diet. The ascending aortae were fixed with OsO(4), embedded in methacrylate and araldite, sectioned, stained with lead hydroxide, and examined with the electron microscope. The descending thoracic aortae were examined by light microscopy. Compared with pair-fed controls, the experimentals showed definite changes which became more marked as the disease progressed. The wall became thicker with wider interlaminar spaces, radial orientation of the smooth muscle cells, progressive loss of desmosomes, and progressive increase in a dense, finely stippled material that coated the edges of the elastic laminae and extended outwards between the muscle cells and separated the ends of these cells from the laminae. This stippled material occurred at the same sites as the increase in PAS-positive and azan-positive material seen with the light microscope. There was an increase in subendothelial and interlaminar collagen, and electron microscopy clearly showed that the cells were smooth muscle and not fibroblasts. The possible bearing of the morphological changes on the formation of aortic aneurysms is discussed.
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PMID:Electron microscope study of the lathyritic rat aorta. 1440 3

The lathyrogenic effect of INAH in the chick embryo may be measured by the increase in the extractibility of collagen from the bones with 1 M NaCl. Incubation of these bones in vitro with carbonyl compounds diminishes the amount of extractible collagen; with D-L-glyceraldehyde the reversal of the INAH effect is complete. This reversal effect is dependent on the time and temperature of incubation and on the quantity of D-L-glyceraldehyde, but is independent of the pH of the incubating medium, the optical form of the glyceraldehyde, or the metabolism of the cells; this suggests that it depends on a simple chemical combination. D-L-glyceraldehyde also reverses completely the extractibility of collagen from the bones of embryos rendered lathyrogenic with BAPN, semicarbazide, and hydrazine hydrate. The hypothesis has been advanced "that lathyrogenic agents act by blocking carbonyl groups on the collagen molecule, thus preventing cross-linking essential to normal maturation; normal maturation may be restored by the addition of carbonyl groups which act by competing either for the lathyrogen or for functional sites on the collagen molecule." In support of this hypothesis, it has been shown that purified lathyritic guinea pig collagen takes up lesser amounts of 2,4-dinitrophenylhydrazine-a compound which combines with carbonyl groups-than does normal collagen; it has been shown that lathyritic collagen still possesses the ability to form segment-long-spacing (SLS) collagen, but that these fibres are much thinner than normal; this is due perhaps to blockade of groups essential for lateral cross-linking of the tropocollagen unit. It has also been shown that normal, purified guinea pig collagen which has been pretreated with INAH, takes up lesser amounts of 2,4-dinitrophenylhydrazine and forms much thinner SLS fibres than the untreated controls.
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PMID:Studies on the mode of action of lathyrogenic compounds. 1446 93

This study extends the use of two lathyrogens, ss-aminopropionitrile (BAPN) and D-penicillamine (DPA) from daily systemic or local-topical administration to long-time acting agents. This was achieved by converting the hydrophilic drugs into lipophilic derivatives. The synthesis of functional derivatives of DPA consisted in esterification with methyl-, hexyl-, or benzyl alcohols in the presence of thionylchloride. The esters formed were hydrochlorides, acidic and soluble in water. During neutralization in vitro or in vivo by tissue fluid, an oily substance is formed that elutes from a hydrogel polymer at a much slower rate than hydroplilic DPA itself. The degree of lipophilicity, measured as a partition coefficient between octanol/water, was highest for hexyl ester and lowest for methyl ester DPA. A single injection of either DPA hexyl ester HCl or 3-hexyl(amino) propionitrile into the full thickness skin incision wound in rats significantly lowered the breaking strength of the wound 12 days after injection, indicating the interference with collagen cross-linking. Both agents injected into the breast adenocarcinoma in Fisher rats significantly inhibited tumor growth without any signs of local or systemic toxicity. We conclude that these lipophilic lathyrogens with prolonged effectiveness are suitable in the treatment of pathologies, consisting of excessively cross-linked or deposited collagen (fibrotic adhesions, strictures, stenosis, and scar contractures) and in the treatment of single, solitary tumors, malignant and benign.
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PMID:Synthesis and evaluation of long-acting D-penicillamine derivatives. 1654 28

The optimal stimulus to repair or regenerate cartilage is not known. We therefore modulated collagen deposition, collagen crosslinking and GAG deposition simultaneously during cartilage matrix production and integrative repair, creating more insight into their role in cartilage repair processes. Insulin-like growth factor 1 (IGF-1; increases proteoglycan and collagen synthesis), beta-aminopropionitrile (BAPN; a reversible inhibitor of collagen crosslinking) and para-nitrophenyl-beta-D-xyloside (PNPX; interferes with proteoglycan production) were used. Bovine articular chondrocytes were cultured in alginate beads for 3 weeks with or without IGF-1, BAPN or PNPX alone and in all possible combinations, followed by 3 weeks in control medium. DNA content, GAG and collagen deposition and collagen crosslinks were determined. Cartilage constructs were cultured under the same conditions and histologically analysed for integration of two opposing cartilage matrices. In alginate cultures, inhibition of collagen crosslinking with BAPN, in combination with promotion of matrix synthesis using IGF1, was most beneficial for matrix deposition. Addition of PNPX was always detrimental for matrix deposition. For integration of opposing cartilage constructs, the combination of BAPN, IGF1 and temporary prevention of proteoglycan formation with PNPX was most beneficial. When a new matrix is produced, proteoglycans are important to retain collagen in the matrix. When two already formed cartilage matrices have to integrate, a temporary absence of proteoglycans and temporary inhibition of collagen crosslinking might be more beneficial in combination with stimulation of collagen production, e.g. by IGF1. Therefore, the choice of soluble factors to promote cartilage regeneration depends on the type of therapy that will be used.
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PMID:Proteoglycan production is required in initial stages of new cartilage matrix formation but inhibits integrative cartilage repair. 1916 Mar 51


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