Treatment of Terminal Peritoneal Carcinomatosis by a Transducible p53-Activating Peptide

Advanced-stage peritoneal carcinomatosis is resistant to current chemotherapy treatment and, in the case of metastatic ovarian cancer, results in a devastating 15%–20% survival rate. Therapeutics that restore genes inactivated during oncogenesis are predicted to be more potent and specific than current therapies. Experiments with viral vectors have demonstrated the theoretical utility of expressing the p53 tumor suppressor gene in cancer cells. However, clinically useful alternative approaches for introducing p53 activity into cancer cells are clearly needed. It has been hypothesized that direct reactivation of endogenous p53 protein in cancer cells will be therapeutically beneficial, but few tests of this hypothesis have been carried out in vivo. We report that a transducible D-isomer RI-TATp53C′ peptide activates the p53 protein in cancer cells, but not normal cells. RI-TATp53C′ peptide treatment of preclinical terminal peritoneal carcinomatosis and peritoneal lymphoma models results in significant increases in lifespan (greater than 6-fold) and the generation of disease-free animals. These proof-of-concept observations show that specific activation of endogenous p53 activity by a macromolecular agent is therapeutically effective in preclinical models of terminal human malignancy. Our results suggest that TAT-mediated transduction may be a useful strategy for the therapeutic delivery of large tumor suppressor molecules to malignant cells in vivo

Anti-listeria Monocytogenes Activity Of Enterocins Microencapsulated By Ionic Gelation

The encapsulation of enterocins synthesized by . Enterococcus faecium CRL1385 through ionic gelation with calcium ions was analyzed. Different enterocins samples were lyophilised and encapsulated using low-methoxyl pectin as the coating material. Lipids present in milk butter were also added to control the release of antimicrobial peptides from the capsules. The morphology of fresh and freeze-dried capsules was examined using light microscopy and scanning electron microscopy, respectively. Antimicrobial activity of encapsulated bacteriocins was assessed against . Listeria monocytogenes 01/155 using the agar diffusion technique and direct contact in microplates. The capsules with higher lipid content showed a more spherical and uniform shape. Pathogen inhibition was observed for capsules prepared with different bacteriocin solutions both on solid (halo diameter = 8.5-13.5 mm) and in an aqueous medium (. ca. 2 log orders decline in . L. monocytogenes viability). The outcomes suggest that bacteriocin encapsulation through ionic gelation can be a potential alternative for the application of these antimicrobial peptides as biopreservatives in food. © 2012 Elsevier Ltd.2912126Anal, A.K., Singh, H., Recent advances in microencapsulation of probiotics for industrial applications and targeted delivery (2007) Trends in Food Science & Technology, 18, pp. 240-251(2002) Official methods of analysis of AOAC international, , AOAC, AOAC International, MarylandAudisio, M.C., Oliver, G., Apella, M.C., Effect of different complex carbon sources on the growth of Enterococcus faecium and on its bacteriocin synthesis (2001) International Journal of Food Microbiology, 63, pp. 235-241Audisio, M.C., Terzolo, H.R., Apella, M.C., Bacteriocin from honeybee beebread Enterococcus avium, active against Listeria monocytogenes (2005) Applied & Environmental Microbiology, 71, pp. 3373-3375Borgogna, M., Bellich, B., Zorzin, L., Lapasin, R., Cesàro, A., Food microencapsulation of bioactive compounds: rheological and thermal characterisation of non-conventional gelling system (2010) Food Chemistry, 122, pp. 416-423Bower, C.K., McGuire, J., Daeschel, M.A., Suppression of Listeria monocytogenes colonization following adsorption of nisin onto silica surfaces (1995) Applied & Environmental Microbiology, 61, pp. 992-997Champagne, C.P., Fustier, P., Microencapsulation for the improved delivery of bioactive compounds into foods (2007) Current Opinion in Biotechnology, 18, pp. 184-190Daba, H., Pandian, S., Gosselin, J.F., Simard, R.E., Huang, J., Lacroix, C., Detection and activity of a bacteriocin produced by Leuconostoc mesenteroides (1991) Applied & Environmental Microbiology, 57, pp. 3450-3455Gálvez, A., Abriouel, H., López, R.L., Omar, N.B., Bacteriocin-based strategies for food biopreservation (2007) International Journal of Food Microbiology, 120, pp. 51-70Gouin, S., Microencapsulation: industrial appraisal of existing technologies and trends (2004) Trends in Food Science & Technology, 15, pp. 330-347Hoffman, A.S., Hydrogels for biomedical applications (2002) Advance Drug Delivery Reviews, 43, pp. 3-12Ibarguren, C., Audisio, M.C., Farfán Torres, M.E., Apella, M.C., Silicates characterization as potential bacteriocin-carriers (2010) Innovative Food Science & Emerging Technologies, 11, pp. 197-202Ibarguren, C., Raya, R.R., Apella, M.C., Audisio, M.C., Enterococcus faecium isolated from honey synthesized bacteriocin-like substances active against different Listeria monocytogenes strains (2010) Journal of Microbiology, 48 (1), pp. 44-52Kopermsub, P., Varissaporn, M., Choochart, W., Potential use of niosomes for encapsulation of nisin and EDTA and their antibacterial activity enhancement (2011) Food Research International, 44, pp. 605-612Langdon, C.J., Levine, D.M., Jones, D.A., Microparticulate feeds for marine suspension-feeders (1985) Journal of Microencapsulation, 2 (1), pp. 1-11Mukai-Correa, R., Prata, A.S., Alvim, I.D., Grosso, C.R.F., Controlled release of protein from hydrocolloid gel microbeads before and after drying (2004) Current Drug Delivery, 1, pp. 265-273da Silva Malheiros, P., Daroit, D.J., Brandelli, A., Food applications of liposome-encapsulated antimicrobial peptides (2010) Trends in Food Science & Technology, 21 (6), pp. 284-292Siragusa, G.R., Dickson, J.S., Inhibition of Listeria monocytogenes on beef tissue by application of organic acids immobilized in a calcium alginate cell (1992) Journal of Food Science, 57, pp. 293-296Talukder, R., Fassihi, R., Gastroretentive delivery systems: hollow beads (2004) Drug Development and Industrial Pharmacy, 30 (4), pp. 405-412Teixeira, M.L., dos Santos, J., Silveira, N.P., Brandelli, A., Phospholipid nanovesicles containing a bacteriocin-like substance for control of Listeria monocytogenes (2008) Innovative Food Science & Emerging Technologies, 9, pp. 49-53Wan, J., Gordon, J., Hickey, M.W., Mawson, R.F., Coventry, M.J., Adsorption of bacteriocins by ingestible silica compounds (1996) Journal of Applied Microbiology, 81, pp. 167-173Willaert, R.G., Baron, G.V., Gel entrapment and micro-encapsulation: methods, applications and engineering principles (1996) Reviews in Chemical Engineering, 12, pp. 1-20

Bacteriocin from Honeybee Beebread Enterococcus avium, Active against Listeria monocytogenes

Enterococcus avium isolated from Apis mellifera beebread produces a thermoresistant bacteriocin with a strain-dependent inhibitory effect on Listeria and without effect on gram-negative bacteria. The bacteriocin appeared to be a polypeptide of about 6 kDa. Genetic analyses revealed no extrachromosomal material in E. avium

Evaluation of superoxide dismutate-like activity in some Copper (II) complexes of aminoacids

Se investigó la actividad superóxido-dismutasa de una serie de complejos de cobre(II) con los aminoácidos glicina, aLanina, valina, isoleucina y serina, utilizando el ensayo de reducción del colorante niTroazultetrazolio por superóxido. Los resultados muestran que todos los complejos investigados poseen la capacidad de dismutar al anión superóxido, generado en el sistema xantinalxantina oxidasa. Los resultados se comparan también con los obtenidos para la enzima superóxido-dismutasa nativa, ensayada en las mismas condiciones experimentales. La lipofilicidad de los complejos fue determinada a partir del estudio de sus coeficientes de partición entre solución fisiológica y n-octanol. Se observó un importante incremento en la lipofilicidad al aumentar la complejidad de los ligandos y también en comparación con la de los aminoácidos libres.The superoxide dismutase-like activity of a series of copper(Il) complexes of the aminoacids glycine, alanine, valine, isoleucine, and serine has been investigated using the nitrobluetetrazolium/superoxide reduction assay. The results show that all the investigated complexes possess the capability to dismutate the superoxide anion generated in the xanthinelxanthine oxidase system. The results are compared with those obtained for the native enzyme superoxide dismutase, tested under the same experimental conditions. The lipophilicity of the complexes was tested determining their partition coefficients between physiological solution and n-octanol. The results show an important increment in lipophilicity with increasing complexity of the ligands and also in comparison with that of the free aminoacids.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Evaluation of superoxide dismutate-like activity in some Copper (II) complexes of aminoacids

Se investigó la actividad superóxido-dismutasa de una serie de complejos de cobre(II) con los aminoácidos glicina, aLanina, valina, isoleucina y serina, utilizando el ensayo de reducción del colorante niTroazultetrazolio por superóxido. Los resultados muestran que todos los complejos investigados poseen la capacidad de dismutar al anión superóxido, generado en el sistema xantinalxantina oxidasa. Los resultados se comparan también con los obtenidos para la enzima superóxido-dismutasa nativa, ensayada en las mismas condiciones experimentales. La lipofilicidad de los complejos fue determinada a partir del estudio de sus coeficientes de partición entre solución fisiológica y n-octanol. Se observó un importante incremento en la lipofilicidad al aumentar la complejidad de los ligandos y también en comparación con la de los aminoácidos libres.The superoxide dismutase-like activity of a series of copper(Il) complexes of the aminoacids glycine, alanine, valine, isoleucine, and serine has been investigated using the nitrobluetetrazolium/superoxide reduction assay. The results show that all the investigated complexes possess the capability to dismutate the superoxide anion generated in the xanthinelxanthine oxidase system. The results are compared with those obtained for the native enzyme superoxide dismutase, tested under the same experimental conditions. The lipophilicity of the complexes was tested determining their partition coefficients between physiological solution and n-octanol. The results show an important increment in lipophilicity with increasing complexity of the ligands and also in comparison with that of the free aminoacids.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Lubrication and load-bearing properties of human salivary pellicles adsorbed ex vivo on molecularly smooth substrata

In a series of Surface Force Balance experiments, material from human whole saliva was adsorbed to molecularly smooth mica substrata (to form an 'adsorbed salivary film'). Measurements were taken of normal (load bearing, Fn) and shear (frictional, Fs*) forces between two interacting surfaces. One investigation involved a salivary film formed by overnight adsorption from undiluted, centrifuged saliva, with the adsorbed film rinsed with pure water before measurement. Measurements were taken under pure water and 70 mM NaNO3. In a second investigation, a film was formed from and measured under a solution of 7% filtered saliva in 10 mM NaNO3. Fn results for both systems showed purely repulsive layers, with an uncompressed thickness of 35-70 nm for the diluted saliva investigation and, prior to the application of shear, 11 nm for the rinsed system. Fs* was essentially proportional to Fn for all systems and independent of shear speed (in the range 100-2000 nm s-1), with coefficients of friction μ ~ 0.24 and μ ~ 0.46 for the unrinsed and rinsed systems, respectively. All properties of the rinsed system remained similar when the pure water measurement environment was changed to 70 mM NaNO3. For all systems studied, shear gave rise to an approximately threefold increase in the range of normal forces, attributed to the ploughing up of adsorbed material during shear to form debris that stood proud of the adsorbed layer. The results provide a microscopic demonstration of the wear process for a salivary film under shear and may be of particular interest for understanding the implications for in vivo oral lubrication under conditions such as rinsing of the mouth cavity. The work is interpreted in light of earlier studies that showed a structural collapse and increase in friction for an adsorbed salivary film in an environment of low ionic strength

Cell type and promoter-specific roles of Ser18 phosphorylation in regulating p53 responses

Phosphorylation of mouse p53 at Ser(18) occurs after DNA damage. To determine the physiological roles of this phosphorylation event in p53-dependent DNA damage responses, a Ser(18) to Ala missense mutation was introduced into the germline of mice. Thymocytes and fibroblasts from the knock-in mice show reduced transactivation of many p53 target genes following DNA damage. p53 protein stabilization and DNA binding are similar in knock-in and wild type mice, but C-terminal acetylation was defective, consistent with a role for Ser(18) in the recruitment of transcriptional co-activators. The apoptotic response of knock-in thymocytes to ionizing radiation is intermediate between that of wild type and p53 null thymocytes. Despite impaired transcriptional and apoptotic responses, the knock-in mice are not prone to spontaneous tumorigenesis. This indicates that neither phosphorylation of p53 on Ser(18) by ATM nor a full transcriptional response is essential to prevent spontaneous tumor formation in mice.</p

Detecting and correcting publication bias in meta-analysis

textPublication bias (PB) makes the resources for meta-analysis (M-A) unreliable in the sense of completion and accuracy, so to investigate, identify and correct PB is a very important issue in M-A. The current study proposed an empirical comparison in both detection and correcting PB, using a Monte Carlo study. Conditions to be manipulated include the number of primary studies, number of missing studies and true effect size. RANNOR in SAS will be used to generate normally distributed random variables and, for each condition, 10,000 M-As will be simulated. Type I error rates are to be calculated for the conditions with no PB and powers were estimated for the conditions with PB and adequate type I error control. Finally, a demonstration of how M-A can and should be used as a part of program evaluations was given.Educational Psycholog

Rendimientos de cultivares de arveja (Pisum sativum L.) en diferentes ambientes de la República Argentina. Campaña 2015/2016

El cultivo de arveja logró ocupar el 32% de lo sembrado en el invierno en el sudeste de Santa Fe y nordeste de la provincia de Buenos Aires en la campaña 2015-2016, llegando a ser más de 88000 has. De estas, entre un 15 y un 20% fueron sembradas con materiales de cotiledón amarillo. Para conocer el comportamiento y adaptación de distintos materiales tanto de cotiledón amarillo como verde en diferentes regiones del país, se llevó a cabo esta red de ensayos.Fil: Prieto, G.. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Alamo, F.. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Apella, C.. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Barrow; ArgentinaFil: Avila, F.. CREA; ArgentinaFil: Brassesco, R.. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Espósito, María Andrea. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Oliveros; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fariña, L.. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Fekete, A.. Instituto Nacional de Tecnología Agropecuaria; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Salta. Estación Experimental Agropecuaria Salta; ArgentinaFil: Figueroa, E.. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Corrientes. Estación Experimental Agropecuaria Mercedes; ArgentinaFil: Maggio, J. C.. Agrar del sur; ArgentinaFil: Martins, L.. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Mortarini, M.. Ojos del salado; ArgentinaFil: Pérez, G.. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Prece, N.. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Norte. Estación Experimental Agropecuaria Pergamino; ArgentinaFil: Real, M.. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Bordenave; ArgentinaFil: Vallejo, M.. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Vizgarra, O.. Instituto Nacional de Tecnología Agropecuaria; Argentin