Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99 Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC 24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.Fil: Sarduy, M. R.. Medical-surgical Research Center; CubaFil: García, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Coca, M. A.. Clinical Investigation Center; CubaFil: Perera, A.. Clinical Investigation Center; CubaFil: Torres, L. A.. Clinical Investigation Center; CubaFil: Valenzuela, C. M.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Baladrón, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Solares, M.. Hospital Materno Ramón González Coro; CubaFil: Reyes, V.. Center For Genetic Engineering And Biotechnology Havana; CubaFil: Hernández, I.. Isotope Center; CubaFil: Perera, Y.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Martínez, Y. M.. Medical-surgical Research Center; CubaFil: Molina, L.. Medical-surgical Research Center; CubaFil: González, Y. M.. Medical-surgical Research Center; CubaFil: Ancízar, J. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Prats, A.. Clinical Investigation Center; CubaFil: González, L.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Casacó, C. A.. Clinical Investigation Center; CubaFil: Acevedo, B. E.. Centro de Ingeniería Genética y Biotecnología; CubaFil: López Saura, P. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; ArgentinaFil: Gómez, R.. Elea Laboratories; ArgentinaFil: Perea Rodríguez, S. E.. Center For Genetic Engineering And Biotechnology Havana; Cuba. Centro de Ingeniería Genética y Biotecnología; Cub

Star Formation and Dynamics in the Galactic Centre

The centre of our Galaxy is one of the most studied and yet enigmatic places in the Universe. At a distance of about 8 kpc from our Sun, the Galactic centre (GC) is the ideal environment to study the extreme processes that take place in the vicinity of a supermassive black hole (SMBH). Despite the hostile environment, several tens of early-type stars populate the central parsec of our Galaxy. A fraction of them lie in a thin ring with mild eccentricity and inner radius ~0.04 pc, while the S-stars, i.e. the ~30 stars closest to the SMBH (<0.04 pc), have randomly oriented and highly eccentric orbits. The formation of such early-type stars has been a puzzle for a long time: molecular clouds should be tidally disrupted by the SMBH before they can fragment into stars. We review the main scenarios proposed to explain the formation and the dynamical evolution of the early-type stars in the GC. In particular, we discuss the most popular in situ scenarios (accretion disc fragmentation and molecular cloud disruption) and migration scenarios (star cluster inspiral and Hills mechanism). We focus on the most pressing challenges that must be faced to shed light on the process of star formation in the vicinity of a SMBH.Comment: 68 pages, 35 figures; invited review chapter, to be published in expanded form in Haardt, F., Gorini, V., Moschella, U. and Treves, A., 'Astrophysical Black Holes'. Lecture Notes in Physics. Springer 201

Traces of past activity in the Galactic Centre

The Milky Way centre hosts a supermassive Black Hole (BH) with a mass of ~4*10^6 M_Sun. Sgr A*, its electromagnetic counterpart, currently appears as an extremely weak source with a luminosity L~10^-9 L_Edd. The lowest known Eddington ratio BH. However, it was not always so; traces of "glorious" active periods can be found in the surrounding medium. We review here our current view of the X-ray emission from the Galactic Center (GC) and its environment, and the expected signatures (e.g. X-ray reflection) of a past flare. We discuss the history of Sgr A*'s past activity and its impact on the surrounding medium. The structure of the Central Molecular Zone (CMZ) has not changed significantly since the last active phase of Sgr A*. This relic torus provides us with the opportunity to image the structure of an AGN torus in exquisite detail.Comment: Invited refereed review. Chapter of the book: "Cosmic ray induced phenomenology in star forming environments" (eds. Olaf Reimer and Diego F. Torres

Relative Abundance, Habitat Use, and Seasonal Variability of Raptor Assemblages In the Flooding Pampas of Argentina

We evaluated the species composition, relative abundance, habitat use, and seasonal variability of raptor assemblages in the Flooding Pampas of Argentina, which represents the southeastern part of the biome known as the Rio de la Plata Grasslands. We conducted seasonal roadside surveys to detect raptors in modified and natural habitats over a 3-yr period from spring 2006 through autumn 2009. We classified raptor species according to their relative abundances and occurrence frequencies, and compared the assemblage composition among land-cover types (croplands, grazing fields, periurban areas, and grasslands) and seasons. The raptor assemblage in the Flooding Pampas comprised 16 species, representing approximately 43% of all raptor species in the biome. The Chimango Caracara (Milvago chimango) was the dominant species in all land-cover types and seasons. The Southern Caracara (Caracara plancus), American Kestrel (Falco sparverius), and Roadside Hawk (Rupornis magnirostris) were all abundant and very frequently observed species, whereas Burrowing Owl (Athene cunicularia), White-tailed Kite (Elanus leucurus), and Long-winged Harrier (Circus buffoni) were less abundant but recorded during most surveys. The remaining raptors (Aplomado Falcon [Falco femoralis], Cinereous Harrier [Circus cinereus], Short-eared Owl [Asio flammeus], Sharp-shinned Hawk [Accipiter striatus], and Snail Kite [Rostrhamus sociabilis]) were much less abundant in the study area. We also recorded four other raptor species (Variable Hawk [Geranoaetus polyosoma], Black-chested Buzzard-Eagle [G. melanoleucus], Striped Owl [Asio clamator], and Barn Owl [Tyto alba]), but only outside of the standard transect surveys. Species composition differed among land-cover types, but we detected no distinct overall seasonal patterns except that species diversity indices were lower in autumn and especially, spring. Milvago chimango was important to determine similarity in assemblage composition within land-cover types, but other less abundant species, such as C. plancus, A. cunicularia, and R. magnirostris, were more important to differentiate land-cover types based on raptor composition. Species diversity was highest in grazing fields and grasslands, and lowest in periurban areas. Our results suggest that although some raptor species appear to benefit from land-cover patterns in the study area, man

Food Habits of the Roadside Hawk (\u3cem\u3eButeo magnirostris\u3c/em\u3e) During the Nonbreeding Season in the Southeastern Pampas of Argentina

Studies of raptors\u27 diet are important for understanding the ecological relationships of the raptors themselves, as well as for assessing the influence of these predators on community ecology (Marti et al. 2007). Although there is abundant information about food habits of raptor species around the world, data on the trophic ecology of neotropical raptors are scarce and the diets of many species are poorly known (del Hoyo et al. 1994, Bierregaard 1998, Bó et al. 2007). The Roadside Hawk (Buteo magnirostris) is a widespread raptor species of Central and South America, ranging from northern Mexico to Río Negro Valley in central Argentina (Thiollay 1994). This medium-sized raptor usually inhabits woodlands and forest edges and, to a lesser extent, open fields near woodlands (Canevari et al. 1991). Near the southern boundary of its range, in the pampas of Buenos Aires Province (Argentina), this raptor is also associated with agroecosystems and grasslands (Narosky and Di Giacomo 1993, Mazar-Barnett and Pearman 2001). Despite being a common species with broad distribution, the Roadside Hawk has been little studied and information about its food habits is scarce and mostly limited to qualitative and anecdotal information (e.g., Haverschmidt 1962, Massoia 1988). In two studies, the diet of Roadside Hawks was quantitatively analyzed. Panasci and Whitacre (2000) reported breeding-season diet in Guatemala through direct observation of nests, and found that the Roadside Hawk delivered mainly small vertebrates (.90%; mainly lizards, frogs, and rodents) to the nest. However, Beltzer (1990) analyzed stomach contents of 22 Roadside Hawks in Argentina throughout one year, and determined that they consumed mostly insects (77%, mainly orthopterans). The objectives of our study were to quantitatively describe the diet of the Roadside Hawk and to estimate its food-niche breadth during the nonbreeding season in Argentina

Red-Backed Hawks Supply Food to Scavenging Chimango Caracaras

Positive interactions between species of terrestrial vertebrates occur frequently and it is common among birds. However, such interactions have generally been overlooked in raptor field studies. We analysed interactions between Red-backed Hawks (Buteo polyosoma) and Chimango Caracaras (Milvago chimango) in order to determine the characteristics of the association between these two South American raptors. We observed 171 bouts of activity, 40 when Red-backed Hawks were feeding and 131 when the Hawks were undertaking other activities. Chimango Caracaras were more often present when Red-backed Hawks were feeding (81%) than during other activities of Red-backed Hawks (69%), but they attacked Red-backed Hawks more frequently during other activities of the Hawks (66%) than when the Hawks were feeding (43%). In addition, the rate of attacks by Chimango Caracaras was higher during other activities of the Hawks (mean = 2.21 attacks per Caracara) than when the Hawks were feeding (mean = 0.68 attacks per Caracara). Duration of feeding activities was not affected significantly by the presence of Chimango Caracaras or by attacks by the Caracaras. During 16 of 40 feeding bouts of Hawks, an average of 1.81 ± 0.23 (s.e.) Caracaras fed on prey discarded by the Hawks. Thus, Red-backed Hawks indirectly supplied food to Chimango Caracaras, which, in turn, reduced their agonistic behaviour towards Hawks. Our findings represent one of few cases reported about facilitative associations among raptors, but it seems likely that it represents a common strategy among these birds

Características diferenciales sanitarias y toxicológicas de drogodependientes en tratamiento y consumo activo

Objetivo. Describir y comparar las características demográficas, toxicológicas y sanitarias de un colectivo de drogodependientes que se encuentra en consumo activo y en diferentes modalidades terapéuticas. Analizar las intervenciones realizadas con estos diferentes colectivos. Diseño. Estudio descriptivo. Emplazamiento. Usuarios que han acudido a la asociación ACLAD de Valladolid. Pacientes. Un total de 1.224 drogodependientes. Mediciones. Revisión de las historias clínicas de los usuarios atendidos en un centro de tratamiento y en un programa de reducción de daños durante un período de 30 meses. Se registran diferentes variables demográficas, toxicológicas y clínicas, se efectúa la comparación entre programas y se valora la evolución de los pacientes. Resultados. Se estudian 1.224 pacientes. Un tercio presenta infección por el virus de la inmunodeficiencia humana; el 63%, marcadores de una hepatitis A pasada, el 48%, marcadores de hepatitis B, y el 68,5% de hepatitis C. En el 39,1% es positiva la prueba de Mantoux. Se observan diferencias en la prevalencia de infecciones entre los usuarios en consumo activo y los usuarios en tratamiento, entre los drogodependientes en diferentes modalidades terapéuticas y en el período del estudio. Conclusiones. Existen claras diferencias en las características demográficas, toxicológicas y sanitarias de los usuarios incluidos en el estudio. Los usuarios que no están en tratamiento de rehabilitación son los que peores condiciones sanitarias tienen. Éstos son los menos estudiados por nuestra parte. En estos años de seguimiento se detecta una leve mejoría de estas condiciones y también una tendencia a la mejora de nuestra intervención

Low-Temperature CO Oxidation

Catalytic low-temperature abatement of carbon monoxide becomes essential in environmental pollution control. CO Oxidation, CO Preferential Oxidation (PROX) and Water Gas Shift (WGS) reaction are the conventional technologies used to remove carbon monoxide at low temperature. Perovskite-type oxides have been extensively studied in the last years as catalysts for these reactions due to their high activity and catalytic stability. This chapter describes the state-of-the-art of using perovskite-based catalysts of general formula ABO3 in these reactions. Key factors such as the type and nature of A and B ions or the formation of oxygen vacancies or interstitials by doping are discussed in the light of the reaction mechanism in each case.Ministerio de Economía y Competitividad (MINECO). España ENE2012-374301-C03-01; ENE2013-47880-C3-2-RJunta de Andalucía PO6-TEP01965; PO9-TEP-5454; TEP-8196European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) PO6-TEP01965; PO9-TEP-5454; TEP-819