Growth Hormone Improves Growth Retardation Induced by Rapamycin without Blocking Its Antiproliferative and Antiangiogenic Effects on Rat Growth Plate

Rapamycin, an immunosuppressant agent used in renal transplantation with antitumoral properties, has been reported to impair longitudinal growth in young individuals. As growth hormone (GH) can be used to treat growth retardation in transplanted children, we aimed this study to find out the effect of GH therapy in a model of young rat with growth retardation induced by rapamycin administration. Three groups of 4-week-old rats treated with vehicle (C), daily injections of rapamycin alone (RAPA) or in combination with GH (RGH) at pharmacological doses for 1 week were compared. GH treatment caused a 20% increase in both growth velocity and body length in RGH animals when compared with RAPA group. GH treatment did not increase circulating levels of insulin-like growth factor I, a systemic mediator of GH actions. Instead, GH promoted the maturation and hypertrophy of growth plate chondrocytes, an effect likely related to AKT and ERK1/2 mediated inactivation of GSK3β, increase of glycogen deposits and stabilization of β-catenin. Interestingly, GH did not interfere with the antiproliferative and antiangiogenic activities of rapamycin in the growth plate and did not cause changes in chondrocyte autophagy markers. In summary, these findings indicate that GH administration improves longitudinal growth in rapamycin-treated rats by specifically acting on the process of growth plate chondrocyte hypertrophy but not by counteracting the effects of rapamycin on proliferation and angiogenesis

LAB-Secretome: a genome-scale comparative analysis of the predicted extracellular and surface-associated proteins of Lactic Acid Bacteria.

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Morphological changes in Salmonella Typhimurium caused by the lantibiotic bovicin HC5 in association with EDTA

Bacteriocins, particularly those produced by Gram-positive bacteria, have in recent years been considered promising antimicrobial agents to inhibit bacterial growth in food, and thus are potential food preservatives. These peptides generally exhibit a spectrum of action limited to Gram-positive bacteria. However, their action can be extended to Gram-negative bacteria through association with chelating agents. In the present study, we evaluated the occurrence of morphological changes on the cell envelope of Salmonella Typhimurium cells treated with bovicin HC5—a lantibiotic from Streptococcus bovis HC5—in association with EDTA. The morphological changes of the cells were visualized by atomic force microscopy (AFM), and the increase in cell membrane permeability was confirmed by the leakage of potassium ions (K+). The images displayed changes in the cell envelope, with increased surface roughness and a decreased cell volume. These changes indicate that EDTA plays a role in the destabilization of the outer membrane, allowing bovicin HC5 to act on the cytoplasmic membrane through the formation of pores, which was confirmed by the detection of potassium in the cell supernatant. These results suggest that bovicin HC5 combined with EDTA has potential for use on Salmonella cells