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Biomedical subjects

A Barbero

Publications and source records attributed to A Barbero.

11 recordsLinked to original sources

Intramolecular cyclization of tert-butyldiphenylallylsilane units and carbonyl groups: allylsilane terminated cyclization versus the ene reaction.

tert-Butyldiphenylsilylcopper reacts with allene to give an allylsilane-vinylcopper intermediate which upon treatment with alpha,beta-unsaturated ketones leads to allylsilane containing ketones resulting from conjugate addition. These oxoallylsilanes bearing the bulky tert-butyldiphenylsilyl group undergo highly selective intramolecular cyclizations when treated with Lewis acid affording unsaturated cyclopentanols. Two reactivity patterns are observed: allylsilane terminated cyclization involving elimination of silicon or an ene reaction without losing the silyl group. The pathway depends on the ability of a hydrogen beta to the carbonyl to be removed in an ene-type process. Alpha,beta-unsaturated acid chlorides lead to silylated cyclopentenones.

Journal Article↗

A tandem allylsilane-vinylsilane difunctionalization by silylcupration of allene followed by reaction with alpha,beta-unsaturated nitriles.

Silylcupration of allene using phenyldimethylsilylcopper 1 followed by BF3-mediated reaction with alpha,beta-unsaturated nitriles at -40 degrees C affords allylsilane-vinylsilane-containing ketones resulting from consecutive addition (1,2 and 1,4) of the intermediate allyl- and vinylcopper species formed in the silylcupration of allene.

Journal Article↗

Growth factor supplemented matrigel improves ectopic skeletal muscle formation--a cell therapy approach.

Following damage to skeletal muscle, satellite cells become activated, migrate towards the injured area, proliferate, and fuse with each other to form myotubes which finally mature into myofibers. We tested a new approach to muscle regeneration by incorporating myoblasts, with or without the exogenous growth factors bFGF or HGF, into three-dimensional gels of reconstituted basement membrane (matrigel). In vitro, bFGF and HGF induced C2C12 myoblast proliferation and migration and were synergistic when used together. In vivo, C2C12 or primary i28 myoblasts were injected subcutaneously together with matrigel and growth factors in the flanks of nude mice. The inclusion of either bFGF or HGF increased the vascularization of the gels. Gels supplemented with bFGF showed myogenesis accompanied by massive mesenchymal cell recruitment and poor organization of the fascicles. Samples containing HGF showed delayed differentiation with respect to controls or bFGF, with increased myoblast proliferation and a significantly higher numbers of cells in myotubes at later time points. HGF samples showed limited mesenchymal cell infiltration and relatively good organization of fascicles. The use of both bFGF and HGF together showed increased numbers of nuclei in myotubes, but with bFGF-mediated fibroblast recruitment dominating. These studies suggest that an appropriate combination of basement membrane components and growth factors could represent a possible approach to enhance survival dispersion, proliferation, and differentiation of myogenic cells during muscle regeneration and/or myoblast transplantation. This model will help develop cell therapy of muscle diseases and open the future to gene therapy approaches.

Animals↗

Human immunodeficiency virus transactivator protein (Tat) stimulates chemotaxis, calcium mobilization, and activation of human polymorphonuclear leukocytes: implications for Tat-mediated pathogenesis.

The extracellular activities of the human immunodeficiency virus (HIV) transactivator protein (Tat) include induction of angiogenesis and stimulation of monocyte migration. Here it is shown that polymorphonuclear leukocytes (PMNL), mostly neutrophils, rapidly invade in response to Tat in vivo and initiate the formation of new vessels. In vitro, Tat was chemotactic for PMNL and induced calcium (Ca(2+)) mobilization. Tat proteins with inactivating substitutions in the arginine-glycine-aspartic acid or basic domain were still active in inducing PMNL migration, whereas Tat peptides mapped the migration and Ca(2+) mobilization activity to a cysteine-rich core domain, previously described as a Tat "chemokine-like" region (peptide CysL(24-51)). Tat and the CysL(24-51) peptide also induced PMNL superoxide production and the release of the angiogenic factors interleukin-8 and vascular endothelial growth factor from PMNL. CysL(24-51) did not induce endothelial cell migration but was angiogenic in vivo. These data indicate that the Tat activity on PMNL is mediated by its chemokine-like region and that PMNL recruitment by Tat is linked to angiogenesis.

Amino Acid Substitution↗

Distinct chemotactic and angiogenic activities of peptides derived from Kaposi's sarcoma virus encoded chemokines.

The vMIPs are chemokine-like proteins expressed by the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) during the lytic phase of viral infection. vMIP-I activates CCR8, a chemokine receptor expressed by Th2 lymphocytes and cultured monocytes. vMIP-II is an agonist for CCR3, a receptor expressed by eosinophils, and an antagonist for several other chemokine receptors. Both are highly angiogenic in the chick chorio-allantoic membrane. We designed and tested three 26-mer peptides, derived from vMIP-I (pK-I), from vMIP-II (pK-II) and from the control MIP-1alpha (pM), spanning key residues of chemokines. pK-I, pK-II and pM all were able to activate a strong chemotactic response in monocytes, higher than parental vMIP-I and II. This corresponded to induction of calcium fluxes in these cells, typical of chemokines. Interestingly, pK-II and pM were also active on PMN neutrophils. In vivo studies (matrigel sponge and rabbit cornea models) showed that pK-I retains the strong angiogenic potential exerted by vMIP-I, while pK-II and pM induced an inflammatory response, probably mediated by PMN recruitment. Our observations indicate that chemokine-derived peptides can show biological activity at pharmacological concentrations. pK-I, in particular, displays the angiogenic activity of full-length vMIP-I, while all peptides appear to have acquired additional properties, stimulating new cellular targets.

Allantois↗

[Effects of phototherapy with blue light on chromosomes from human lymphocytes].

The dangerous effects of phototherapy have been matter of discussion in recent years. In order to evaluate its in vitro action on the human DNA, the authors have performed the karyotypic analysis on 20 cultures of lymphocytes. In different times 16 cultures have been exposed to the action of a "blue light" fluorescent lamp, commonly used for the treatment of neonatal jaundice. The authors have not evidenced any morphological or numerical change of the karyotype in any of the cultures.

Adult↗