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Sample records for aminopropionitrile

  1. The effect of beta-aminopropionitrile on lung development in the rat.

    OpenAIRE

    Das, R. M.

    1980-01-01

    beta-Aminopropionitrile (beta APN) was administered intraperitoneally to rats on postnatal days 1, 3, and 5. Body weight, lung volume, lung weight, number of alveoli per unit area and volume, total number of alveoli in the lung, and the total length of elastic fibers in the lung decreased, and the average alveolar volume increased in comparison with control animals similarly treated with saline. From Day 2 of age to Day 6 the total length of elastic fibers increased in control lungs but remai...

  2. The effects of beta-aminopropionitrile on the growing rat lung.

    OpenAIRE

    Kida, K; Thurlbeck, W. M.

    1980-01-01

    beta-Aminopropionitrile (beta APN), 500 ng/g body weight was injected intraperitoneally into male rats every 2 days between 2 and 28 days after birth. The lungs were examined structurally and functionally and compared with the lungs of control animals given injections of saline and 28-day-old normal male rats which were not given injections. Lungs volumes, both distended with air at 30 cm H2O and with formalin at 25 cm H2O, were increased in beta APN-treated animals. The architecture of the l...

  3. Mechanisms for the inversion of chirality: Global reaction route mapping of stereochemical pathways in a probable chiral extraterrestrial molecule, 2-aminopropionitrile

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, Ramanpreet; Vikas, E-mail: qlabspu@pu.ac.in, E-mail: qlabspu@yahoo.com [Quantum Chemistry Group, Department of Chemistry and Centre of Advanced Studies in Chemistry, Panjab University, Chandigarh 160014 (India)

    2015-02-21

    2-Aminopropionitrile (APN), a probable candidate as a chiral astrophysical molecule, is a precursor to amino-acid alanine. Stereochemical pathways in 2-APN are explored using Global Reaction Route Mapping (GRRM) method employing high-level quantum-mechanical computations. Besides predicting the conventional mechanism for chiral inversion that proceeds through an achiral intermediate, a counterintuitive flipping mechanism is revealed for 2-APN through chiral intermediates explored using the GRRM. The feasibility of the proposed stereochemical pathways, in terms of the Gibbs free-energy change, is analyzed at the temperature conditions akin to the interstellar medium. Notably, the stereoinversion in 2-APN is observed to be more feasible than the dissociation of 2-APN and intermediates involved along the stereochemical pathways, and the flipping barrier is observed to be as low as 3.68 kJ/mol along one of the pathways. The pathways proposed for the inversion of chirality in 2-APN may provide significant insight into the extraterrestrial origin of life.

  4. Mechanisms for the inversion of chirality: global reaction route mapping of stereochemical pathways in a probable chiral extraterrestrial molecule, 2-aminopropionitrile.

    Science.gov (United States)

    Kaur, Ramanpreet; Vikas

    2015-02-21

    2-Aminopropionitrile (APN), a probable candidate as a chiral astrophysical molecule, is a precursor to amino-acid alanine. Stereochemical pathways in 2-APN are explored using Global Reaction Route Mapping (GRRM) method employing high-level quantum-mechanical computations. Besides predicting the conventional mechanism for chiral inversion that proceeds through an achiral intermediate, a counterintuitive flipping mechanism is revealed for 2-APN through chiral intermediates explored using the GRRM. The feasibility of the proposed stereochemical pathways, in terms of the Gibbs free-energy change, is analyzed at the temperature conditions akin to the interstellar medium. Notably, the stereoinversion in 2-APN is observed to be more feasible than the dissociation of 2-APN and intermediates involved along the stereochemical pathways, and the flipping barrier is observed to be as low as 3.68 kJ/mol along one of the pathways. The pathways proposed for the inversion of chirality in 2-APN may provide significant insight into the extraterrestrial origin of life. PMID:25702015

  5. The lysyl oxidase inhibitor β-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats.

    Science.gov (United States)

    Miana, María; Galán, María; Martínez-Martínez, Ernesto; Varona, Saray; Jurado-López, Raquel; Bausa-Miranda, Belén; Antequera, Alfonso; Luaces, María; Martínez-González, José; Rodríguez, Cristina; Cachofeiro, Victoria

    2015-06-01

    Extracellular matrix (ECM) remodelling of the adipose tissue plays a pivotal role in the pathophysiology of obesity. The lysyl oxidase (LOX) family of amine oxidases, including LOX and LOX-like (LOXL) isoenzymes, controls ECM maturation, and upregulation of LOX activity is essential in fibrosis; however, its involvement in adipose tissue dysfunction in obesity is unclear. In this study, we observed that LOX is the main isoenzyme expressed in human adipose tissue and that its expression is strongly upregulated in samples from obese individuals that had been referred to bariatric surgery. LOX expression was also induced in the adipose tissue from male Wistar rats fed a high-fat diet (HFD). Interestingly, treatment with β-aminopropionitrile (BAPN), a specific and irreversible inhibitor of LOX activity, attenuated the increase in body weight and fat mass that was observed in obese animals and shifted adipocyte size toward smaller adipocytes. BAPN also ameliorated the increase in collagen content that was observed in adipose tissue from obese animals and improved several metabolic parameters - it ameliorated glucose and insulin levels, decreased homeostasis model assessment (HOMA) index and reduced plasma triglyceride levels. Furthermore, in white adipose tissue from obese animals, BAPN prevented the downregulation of adiponectin and glucose transporter 4 (GLUT4), as well as the increase in suppressor of cytokine signaling 3 (SOCS3) and dipeptidyl peptidase 4 (DPP4) levels, triggered by the HFD. Likewise, in the TNFα-induced insulin-resistant 3T3-L1 adipocyte model, BAPN prevented the downregulation of adiponectin and GLUT4 and the increase in SOCS3 levels, and consequently normalised insulin-stimulated glucose uptake. Therefore, our data provide evidence that LOX plays a pathologically relevant role in the metabolic dysfunction induced by obesity and emphasise the interest of novel pharmacological interventions that target adipose tissue fibrosis and LOX activity for

  6. The lysyl oxidase inhibitor β-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats

    Directory of Open Access Journals (Sweden)

    María Miana

    2015-06-01

    Full Text Available Extracellular matrix (ECM remodelling of the adipose tissue plays a pivotal role in the pathophysiology of obesity. The lysyl oxidase (LOX family of amine oxidases, including LOX and LOX-like (LOXL isoenzymes, controls ECM maturation, and upregulation of LOX activity is essential in fibrosis; however, its involvement in adipose tissue dysfunction in obesity is unclear. In this study, we observed that LOX is the main isoenzyme expressed in human adipose tissue and that its expression is strongly upregulated in samples from obese individuals that had been referred to bariatric surgery. LOX expression was also induced in the adipose tissue from male Wistar rats fed a high-fat diet (HFD. Interestingly, treatment with β-aminopropionitrile (BAPN, a specific and irreversible inhibitor of LOX activity, attenuated the increase in body weight and fat mass that was observed in obese animals and shifted adipocyte size toward smaller adipocytes. BAPN also ameliorated the increase in collagen content that was observed in adipose tissue from obese animals and improved several metabolic parameters – it ameliorated glucose and insulin levels, decreased homeostasis model assessment (HOMA index and reduced plasma triglyceride levels. Furthermore, in white adipose tissue from obese animals, BAPN prevented the downregulation of adiponectin and glucose transporter 4 (GLUT4, as well as the increase in suppressor of cytokine signaling 3 (SOCS3 and dipeptidyl peptidase 4 (DPP4 levels, triggered by the HFD. Likewise, in the TNFα-induced insulin-resistant 3T3-L1 adipocyte model, BAPN prevented the downregulation of adiponectin and GLUT4 and the increase in SOCS3 levels, and consequently normalised insulin-stimulated glucose uptake. Therefore, our data provide evidence that LOX plays a pathologically relevant role in the metabolic dysfunction induced by obesity and emphasise the interest of novel pharmacological interventions that target adipose tissue fibrosis and LOX

  7. The lysyl oxidase inhibitor β-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats

    OpenAIRE

    María Miana; María Galán; Ernesto Martínez-Martínez; Saray Varona; Raquel Jurado-López; Belén Bausa-Miranda; Alfonso Antequera; María Luaces; José Martínez-González; Cristina Rodríguez; Victoria Cachofeiro

    2015-01-01

    ABSTRACT Extracellular matrix (ECM) remodelling of the adipose tissue plays a pivotal role in the pathophysiology of obesity. The lysyl oxidase (LOX) family of amine oxidases, including LOX and LOX-like (LOXL) isoenzymes, controls ECM maturation, and upregulation of LOX activity is essential in fibrosis; however, its involvement in adipose tissue dysfunction in obesity is unclear. In this study, we observed that LOX is the main isoenzyme expressed in human adipose tissue and that its expressi...

  8. The lathyrogenic effect of isonicotinic acid hydrazide (INAH) on the chick embryo and its reversal by pyridoxal.

    Science.gov (United States)

    LEVENE, C I

    1961-04-01

    When applied to the chorio-allantoic membrane of the chick embryo, isoniazid was shown to produce an increase in the fragility of the embryo and in the amount of collagen which was extractable from the bones with cold 1 M sodium chloride. The administration of pyridoxal reversed these phenomena almost completely. The effect of isoniazid differed from that of beta-aminopropionitrile in that the latter was of greater magnitude, and was not affected by pyridoxal; whereas beta-aminopropionitrile caused skeletal deformities, isoniazid even at 12 times the concentration produced no deformities. The aldehyde group of pyridoxal was shown to be necessary for its interaction with isoniazid.

  9. ポリアクリルアミド ゲル ニヨル パパイン ノ コテイカ

    OpenAIRE

    "河邊,誠一郎/河邊,要太郎"; "カワベ,セイイチロウ/カワベ,ヨウタロウ/ウサミ,ショウジ"; "Kawabe,Seiichiro/Kawabe,Yohtaro/Usami,Shoji"

    1981-01-01

    "Papain was immobilized in crosslinked polyacrylamide gel by entrapment. The method is based on the polymerization of acrylamide in the presence of varying amount of N, N'-methylene bisacrylamide, 3-dimethyl aminopropionitrile and potassumpersulfate as crosslinking monomer, polymerization accelerator and initiator, in an aqueous medium containing the dissolved papain. It appeared that the only acrylamide as polymerization monomer decreased the activity of papain. Then, to protect papain again...

  10. Development of topical BAPN delivery system for acute spinal cord injury in dogs.

    Science.gov (United States)

    Chvapil, M; Weinstein, P R; Misiorowski, R L; Telles, D; Rankin, L; Stoy, V

    1984-09-01

    Topical sustained release of various medications by a subdurally implantable device at the site of spinal cord injury is considered advantageous in the treatment of early symptoms of tissue damage. A typical case is the interference with collagenous scar by beta-aminopropionitrile, inhibiting collagen polymerization. Four materials, silicone, polyethylene, polytetrafluoroethylene (PTFE), and polyacrylonitrile-based hydrogel were evaluated for biocompatibility in subcutaneous implantations. The hydrogel, the least reactive, was then compared with silicone sheets as subcural implants. The histology favored the hydrogel as the most inert material, which was then used for the construction of soft, pliable pouches, releasing the drug through the hydrated wall at a rate controlled by an osmotic pump. PMID:6544776

  11. Comparison of kinetic properties of amine oxidases from sainfoin and lentil and immunochemical characterization of copper/quinoprotein amine oxidases.

    Science.gov (United States)

    Zajoncová, L; Frébort, I; Luhová, L; Sebela, M; Galuszka, P; Pec, P

    1999-01-01

    Kinetic properties of novel amine oxidase isolated from sainfoin (Onobrychis viciifolia) were compared to those of typical plant amine oxidase (EC 1.4.3.6) from lentil (Lens culinaris). The amine oxidase from sainfoin was active toward substrates, such as 1,5-diaminopentane (cadaverine) with K(m) of 0.09 mM and 1,4-diaminobutane (putrescine) with K(m) of 0.24 mM. The maximum rate of oxidation for cadaverine at saturating concentration was 2.7 fold higher than that of putrescine. The amine oxidase from lentil had the maximum rate for putrescine comparable to the rate of sainfoin amine oxidase with the same substrate. Both amine oxidases, like other plant Cu-amine oxidases, were inhibited by substrate analogs (1,5-diamino-3-pentanone, 1,4-diamino-2-butanone and aminoguanidine), Cu2+ chelating agents (diethyltriamine, 1,10-phenanthroline, 8-hydroxyquinoline, 2,2'-bipyridyl, imidazole, sodium cyanide and sodium azide), some alkaloids (L-lobeline and cinchonine), some lathyrogens (beta-aminopropionitrile and aminoacetonitrile) and other inhibitors (benzamide oxime, acetone oxime, hydroxylamine and pargyline). Tested by Ouchterlony's double diffusion in agarose gel, polyclonal antibodies against the amine oxidase from sainfoin, pea and grass pea cross-reacted with amine oxidases from several other Fabaceae and from barley (Hordeum vulgare) of Poaceae, while amine oxidase from the filamentous fungus Aspergillus niger did not cross-react at all. However, using Western blotting after SDS-PAGE with rabbit polyclonal antibodies against the amine oxidase from Aspergillus niger, some degree of similarity of plant amine oxidases from sainfoin, pea, field pea, grass pea, fenugreek, common melilot, white sweetclover and Vicia panonica with the A. niger amine oxidase was confirmed. PMID:10092944

  12. Collagen telopeptides (cross-linking sites) play a role in collagen gel lattice contraction

    Science.gov (United States)

    Woodley, D. T.; Yamauchi, M.; Wynn, K. C.; Mechanic, G.; Briggaman, R. A.

    1991-01-01

    Solubilized interstitial collagens will form a fibrillar, gel-like lattice when brought to physiologic conditions. In the presence of human dermal fibroblasts the collagen lattice will contract. The rate of contraction can be determined by computer-assisted planemetry. The mechanisms involved in contraction are as yet unknown. Using this system it was found that the rate of contraction was markedly decreased when collagen lacking telopeptides was substituted for native collagen. Histidinohydroxylysinonorleucine (HHL) is a major stable trifunctional collagen cross-link in mature skin that involves a carboxyl terminal, telopeptide site 16c, the sixteenth amino acid residue from the carboxy terminal of the telopeptide region of alpha 1 (I) in type I collagen. Little, if any, HHL was present in native, purified, reconstituted, soluble collagen fibrils from 1% acetic acid-extracted 2-year-old bovine skin. In contrast, HHL cross-links were present (0.22 moles of cross-link per mole of collagen) in lattices of the same collagen contracted by fibroblasts. However, rat tail tendon does not contain HHL cross-links, and collagen lattices made of rat tail tendon collagen are capable of contraction. This suggests that telopeptide sites, and not mature HHL cross-links per se, are essential for fibroblasts to contract collagen lattices. Beta-aminopropionitrile fumarate (BAPN), a potent lathyrogen that perturbs collagen cross-linking by inhibition of lysyl oxidase, also inhibited the rate of lattice cell contraction in lattices composed of native collagen. However, the concentrations of BAPN that were necessary to inhibit the contraction of collagen lattices also inhibited fibroblast growth suggestive of cellular toxicity. In accordance with other studies, we found no inhibition of the rate of lattice contraction when fibronectin-depleted serum was used. Electron microscopy of contracted gels revealed typical collagen fibers with a characteristic axial periodicity. The data

  13. Intracellular lysyl oxidase: Effect of a specific inhibitor on nuclear mass in proliferating cells

    Energy Technology Data Exchange (ETDEWEB)

    Saad, Fawzy A. [Laboratory for the Study of Skeletal Disorders and Rehabilitation, Department of Orthopedics, Children' s Hospital Boston, 300 Longwood Avenue EN926, Boston, MA 02115 (United States); Harvard Medical School, Boston, MA 02115 (United States); Torres, Marie [Laboratory for the Study of Skeletal Disorders and Rehabilitation, Department of Orthopedics, Children' s Hospital Boston, 300 Longwood Avenue EN926, Boston, MA 02115 (United States); Wang, Hao [Laboratory for the Study of Skeletal Disorders and Rehabilitation, Department of Orthopedics, Children' s Hospital Boston, 300 Longwood Avenue EN926, Boston, MA 02115 (United States); Harvard Medical School, Boston, MA 02115 (United States); Graham, Lila, E-mail: lilagraham@cs.com [Laboratory for the Study of Skeletal Disorders and Rehabilitation, Department of Orthopedics, Children' s Hospital Boston, 300 Longwood Avenue EN926, Boston, MA 02115 (United States); Harvard Medical School, Boston, MA 02115 (United States)

    2010-06-11

    LOX, the principal enzyme involved in crosslinking of collagen, was the first of several lysyl oxidase isotypes to be characterized. Its active form was believed to be exclusively extracellular. Active LOX was later reported to be present in cell nuclei; its function there is unknown. LOX expression opposes the effect of mutationally activated Ras, which is present in about 30% of human cancers. The mechanism of LOX in countering the action of Ras is also unknown. In the present work, assessment of nuclear protein for possible effects of lysyl oxidase activity led to the discovery that proliferating cells dramatically increase their nuclear protein content when exposed to BAPN ({beta}-aminopropionitrile), a highly specific lysyl oxidase inhibitor that reportedly blocks LOX inhibition of Ras-induced oocyte maturation. In three cell types (PC12 cells, A7r5 smooth muscle cells, and NIH 3T3 fibroblasts), BAPN caused a 1.8-, 1.7-, and 2.1-fold increase in total nuclear protein per cell, respectively, affecting all major components in both nuclear matrix and chromatin fractions. Since nuclear size is correlated with proliferative status, enzyme activity restricting nuclear growth may be involved in the lysyl oxidase tumor suppressive effect. Evidence is also presented for the presence of apparent lysyl oxidase isotype(s) containing a highly conserved LOX active site sequence in the nuclei of PC12 cells, which do not manufacture extracellular lysyl oxidase substrates. Results reported here support the hypothesis that nuclear lysyl oxidase regulates nuclear growth, and thereby modulates cell proliferation.

  14. Lathyrism-induced alterations in collagen cross-links influence the mechanical properties of bone material without affecting the mineral

    Science.gov (United States)

    Paschalis, E.P.; Tatakis, D.N.; Robins, S.; Fratzl, P.; Manjubala, I.; Zoehrer, R.; Gamsjaeger, S.; Buchinger, B.; Roschger, A.; Phipps, R.; Boskey, A.L.; Dall'Ara, E.; Varga, P.; Zysset, P.; Klaushofer, K.; Roschger, P.

    2011-01-01

    In the present study a rat animal model of lathyrism was employed to decipher whether anatomically confined alterations in collagen cross-links are sufficient to influence the mechanical properties of whole bone. Animal experiments were performed under an ethics committee approved protocol. Sixty-four female (47 day old) rats of equivalent weights were divided into four groups (16 per group): Controls were fed a semi-synthetic diet containing 0.6% calcium and 0.6% phosphorus for 2 or 4 weeks and β-APN treated animals were fed additionally with β-aminopropionitrile (0.1% dry weight). At the end of this period the rats in the four groups were sacrificed, and L2–L6 vertebra were collected. Collagen cross-links were determined by both biochemical and spectroscopic (Fourier transform infrared imaging (FTIRI)) analyses. Mineral content and distribution (BMDD) were determined by quantitative backscattered electron imaging (qBEI), and mineral maturity/crystallinity by FTIRI techniques. Micro-CT was used to describe the architectural properties. Mechanical performance of whole bone as well as of bone matrix material was tested by vertebral compression tests and by nano-indentation, respectively. The data of the present study indicate that β-APN treatment changed whole vertebra properties compared to non-treated rats, including collagen cross-links pattern, trabecular bone volume to tissue ratio and trabecular thickness, which were all decreased (p < 0.05). Further, compression tests revealed a significant negative impact of β-APN treatment on maximal force to failure and energy to failure, while stiffness was not influenced. Bone mineral density distribution (BMDD) was not altered either. At the material level, β-APN treated rats exhibited increased Pyd/Divalent cross-link ratios in areas confined to a newly formed bone. Moreover, nano-indentation experiments showed that the E-modulus and hardness were reduced only in newly formed bone areas under the influence