Treatment for chronic hepatitis B infection

Más de 400 millones de personas en el mundo están infectadas crónicamente por el virus de la hepatitis B (VHB) (1,2). El virus es responsable de 300.000casos de cáncer hepático cada año, aproximadamente, y de un número similar de hemorragias gastrointestinales y casos de ascitis. La mortalidad atribuible es de 25% (1). La infección por VHB es una de las infecciones más comunes en el mundo, según la Organización Mundial de la Salud (OMS) una tercera parte de lapoblación está infectada por VHB y, aproximadamente,5% esta crónicamente infectada (1-3). En Colombiala tasa nacional de hepatitis B para el 2002es de 2,6 por 100.000 habitantes con una mayor frecuencia de infección hacia las costas y la región amazónica (4). Afortunadamente, existe una vacuna recombinante contra el VHB que ha demostrado una efectividad de 95%. Más de 90 países en el mundo tienen programas de vacunación universal para todos los recién nacidos (3,5). La vacuna para hepatitis B está incluida en el programa ampliado de inmunizaciones en Colombia desde 1993.Q3Artículo de revisión201-21

On the existence of supersolid helium-4 monolayer films

Extensive Monte Carlo simulations of helium-4 monolayer films adsorbed on weak substrates have been carried out, aimed at ascertaining the possible occurrence of a quasi-two-dimensional supersolid phase. Only crystalline films not registered with underlying substrates are considered. Numerical results yield strong evidence that helium-4 will not form a supersolid film on {any} substrate strong enough to stabilize a crystalline layer. On weaker substrates, continuous growth of a liquid film takes place

Solidification of small para-H2 clusters at zero temperature

We have determined the ground-state energies of para-H$_2$ clusters at zero temperature using the diffusion Monte Carlo method. The liquid or solid character of each cluster is investigated by restricting the phase through the use of proper importance sampling. Our results show inhomogeneous crystallization of clusters, with alternating behavior between liquid and solid phases up to N=55. From there on, all clusters are solid. The ground-state energies in the range N=13--75 are established and the stable phase of each cluster is determined. In spite of the small differences observed between the energy of liquid and solid clusters, the corresponding density profiles are significantly different, feature that can help to solve ambiguities in the determination of the specific phase of H$_2$ clusters.Comment: 17 pages, accepted for publication in J. Phys. Chem.

On the possible "supersolid" character of parahydrogen clusters

We present results of a theoretical study of structural and superfluid properties of parahydrogen clusters comprising 25, 26 and 27 molecules at low temperature. The microscopic model utilized here is based on the Silvera-Goldman pair potential. Numerical results are obtained by means of Quantum Monte Carlo simulations, making use of the continuous-space Worm Algorithm. The clusters are superfluid in the low temperature limit, but display markedly different physical behaviours. For N=25 and 27, superfluidity at low temperature arises as clusters melt, i.e., become progressively liquid-like as a result of quantum effects. On the other hand, for N = 26 the cluster remains rigid and solid-like. We argue that this cluster can be regarded as a mesoscopic "supersolid". This physical picture is supported by results of simulations in which a single parahydrogen molecule in the cluster is isotopically substituted.Comment: 18 pages, 7 figure

Pharmacokinetics and pharmacodynamics of antibacterial agents: on account of febrile neutropenic patients

La neutropenia febril es una complicación grave de la terapia antineoplásica que se presenta más frecuentemente en pacientes con neoplasias hematológicas, asociada a tasas elevadas de mortalidad. Uno de los factores descritos como causa de fracasos terapéuticos de la terapia antimicrobiana es la inadecuada concentración tisular de los antimicrobianos que a su vez se correlaciona con bajas concentraciones en el líquido intersticial en el caso de los fármacos hidrofílicos. En pacientes críticamente enfermos se puede presentar acumulación compartimental de líquidos que a su vez se puede asociar con aumento en el volumen de distribución de los medicamentos o alteraciones en la depuración de los mismos. Se revisan los parámetros farmacocinéticos y farmacodinámicos de los antimicrobianos que pueden ser usados como herramienta para optimizar la eficacia de la terapia antiinfecciosa en busca de disminuir la tasa de fracasos y la selección de cepas resistentes.Q4537-545Febrile neutropenia is a serious complication of antineoplastic therapy and it is more commonly found in hematologic patients, associated with high mortality rates. Inadequate tissue concentration of antimicrobials has been described as a cause of therapeutic failure which also has been related to a low interstitial concentration for hydrophilic antibiotics. In critically ill patients it may occur an accumulation of compartmental fluids which can be related to an increase in the distribution volume or changes in clearance of antimicrobials. Pharmacokinetic and pharmacodynamic parameters of antimicrobials are reviewed, which can be used as a tool to optimize the efficacy of antimicrobial therapy in order to avoid failures and resistance selection

The Mare as a Model for Luteinized Unruptured Follicle Syndrome: Intrafollicular Endocrine Milieu.

Luteinized unruptured follicle (LUF) syndrome is a recurrent anovulatory dysfunction that affects up to 23% of women with normal menstrual cycles and up to 73% with endometriosis. Mechanisms underlying the development of LUF syndrome in mares were studied to provide a potential model for human anovulation. The effect of extended increase in circulating LH achieved by administration of recombinant equine LH (reLH) or a short surge of LH and decrease in progesterone induced by prostaglandin F2α (PGF2α) on LUF formation (Experiment 1), identification of an optimal dose of COX-2 inhibitor (flunixin meglumine, FM; to block the effect of prostaglandins) for inducing LUFs (Experiment 2), and evaluation of intrafollicular endocrine milieu in LUFs (Experiment 3) were investigated. In Experiment 1, mares were treated with reLH from Day 7 to Day 15 (Day 0=ovulation), PGF2α on Day 7, or in combination. In Experiment 2, FM at doses of 2.0 or 3.0 mg/kg every 12 h and human chorionic gonadotropin (hCG) (1500 IU) were administered after a follicle ≥32 mm was detected. In Experiment 3, FM at a dose of 2.0 mg/kg every 12 h plus hCG was used to induce LUFs and investigate the intrafollicular endocrine milieu. No LUFs were induced by reLH or PGF2α treatment; however, LUFs were induced in 100% of mares using FM. Intrafollicular PGF2α metabolite, PGF2α, and PGE2 were lower and the ratio of PGE2:PGF2α was higher in the induced LUF group. Higher levels of intrafollicular E2 and total primary sex steroids were observed in the induced LUF group along with a tendency for higher levels of GH, cortisol, and T; however, LH, PRL, VEGF-A, and NO did not differ between groups. In conclusion, this study reveals part of the intrafollicular endocrine milieu and the association of prostaglandins in LUF formation, and indicates that the mare might be an appropriate model for studying the poorly understood LUF syndrome

An integrative approach to species-level systematics reveals the depth of diversification in an Andean thamnophilid, the Long-tailed Antbird

Abstract. The geographic range of the Long-tailed Antbird (Drymophila caudata) extends from the Paria Mountains of Venezuela south through the Andes to northern Bolivia, a geographic and elevational distribution unique in the antbirds (Thamnophilidae). Plumage variation among most populations is not obvious, and although eight subspecies have been described, half have been synonymized. We took a multidimensional approach to reexamining the taxonomy of the complex. We identified lineages by evaluating divergence in mtDNA, and defined study groups within them to take into account previously described plumage differences. We then assessed the taxonomic status of principal lineages and study groups by comparing vocal differences among them to established taxonomic "yardsticks" for thamnophilid antbirds. Finally, we related taxa to the ecology of the regions in which they occur. The outcomes revealed substantial diversification, sufficient for recognition of four species, three restricted to the north and one widespread along the main body of the Andes extending from northwestern Colombia south to Bolivia. Speciation in Andean Drymophila antbirds is partially associated with elevational and environmental divergence. The results provide valuable inputs to mapping and understanding avian evolution in the Andes and demonstrate the value of a multifaceted approach in solving taxonomic problems. Resumen. La distribución geográfica de Drymophila caudata se extiende desde las montañas de Paria en Venezuela hacia el sur a lo largo de la cordillera de los Andes hasta el norte de Bolivia, conformando un patrón de distribución geográfico y altitudinal único en los Thamnophilidae. La variación en el plumaje entre la mayoría de las poblaciones no es obvia y a pesar de que ocho subespecies han sido descritas, la mitad han sido invalidadas. Nosotros optamos por una estrategia multidimensional para reexaminar la taxonomía del complejo. Primero, identificamos linajes con base en su divergencia en ADNmt y grupos de estudio dentro de cada linaje con base en diferencias de plumaje previamente descritas. Después, evaluamos el estatus taxonómico de cada linaje y de cada grupo de estudio mediante comparaciones de las diferencias vocales entre ellos con estándares establecidos para los thamnophílidos. Finalmente, comparamos la ecología de los taxones definidos con base en diferencias climáticas entre sus áreas de distribución. Los resultados revelan un nivel considerable de diversificación, suficiente para el reconocimiento de cuatro especies, tres de ellas restringidas a las montañas del norte y una ampliamente distribuida a lo largo de los Andes desde el noroeste de Colombia hasta Bolivia. El proceso de especiación en los thamnophílidos andinos del género Drymophila está parcialmente asociado con procesos de divergencia altitudinal y ambiental. Estos resultados son valiosos para entender la evolución de las aves en los Andes y demuestran el valor que tienen las estrategias multidimensionales para resolver incertidumbres taxonómicas

The Mare as a Model for Luteinized Unruptured Follicle Syndrome: Intrafollicular Endocrine Milieu.

Luteinized unruptured follicle (LUF) syndrome is a recurrent anovulatory dysfunction that affects up to 23% of women with normal menstrual cycles and up to 73% with endometriosis. Mechanisms underlying the development of LUF syndrome in mares were studied to provide a potential model for human anovulation. The effect of extended increase in circulating LH achieved by administration of recombinant equine LH (reLH) or a short surge of LH and decrease in progesterone induced by prostaglandin F2α (PGF2α) on LUF formation (Experiment 1), identification of an optimal dose of COX-2 inhibitor (flunixin meglumine, FM; to block the effect of prostaglandins) for inducing LUFs (Experiment 2), and evaluation of intrafollicular endocrine milieu in LUFs (Experiment 3) were investigated. In Experiment 1, mares were treated with reLH from Day 7 to Day 15 (Day 0=ovulation), PGF2α on Day 7, or in combination. In Experiment 2, FM at doses of 2.0 or 3.0 mg/kg every 12 h and human chorionic gonadotropin (hCG) (1500 IU) were administered after a follicle ≥32 mm was detected. In Experiment 3, FM at a dose of 2.0 mg/kg every 12 h plus hCG was used to induce LUFs and investigate the intrafollicular endocrine milieu. No LUFs were induced by reLH or PGF2α treatment; however, LUFs were induced in 100% of mares using FM. Intrafollicular PGF2α metabolite, PGF2α, and PGE2 were lower and the ratio of PGE2:PGF2α was higher in the induced LUF group. Higher levels of intrafollicular E2 and total primary sex steroids were observed in the induced LUF group along with a tendency for higher levels of GH, cortisol, and T; however, LH, PRL, VEGF-A, and NO did not differ between groups. In conclusion, this study reveals part of the intrafollicular endocrine milieu and the association of prostaglandins in LUF formation, and indicates that the mare might be an appropriate model for studying the poorly understood LUF syndrome

In vitro modeling of endothelial interaction with macrophages and pericytes demonstrates Notch signaling function in the vascular microenvironment.

Angiogenesis is regulated by complex interactions between endothelial cells and support cells of the vascular microenvironment, such as tissue myeloid cells and vascular mural cells. Multicellular interactions during angiogenesis are difficult to study in animals and challenging in a reductive setting. We incorporated stromal cells into an established bead-based capillary sprouting assay to develop assays that faithfully reproduce major steps of vessel sprouting and maturation. We observed that macrophages enhance angiogenesis, increasing the number and length of endothelial sprouts, a property we have dubbed "angiotrophism." We found that polarizing macrophages toward a pro-inflammatory profile further increased their angiotrophic stimulation of vessel sprouting, and this increase was dependent on macrophage Notch signaling. To study endothelial/pericyte interactions, we added vascular pericytes directly to the bead-bound endothelial monolayer. These pericytes formed close associations with the endothelial sprouts, causing increased sprout number and vessel caliber. We found that Jagged1 expression and Notch signaling are essential for the growth of both endothelial cells and pericytes and may function in their interaction. We observed that combining endothelial cells with both macrophages and pericytes in the same sprouting assay has multiplicative effects on sprouting. These results significantly improve bead-capillary sprouting assays and provide an enhanced method for modeling interactions between the endothelium and the vascular microenvironment. Achieving this in a reductive in vitro setting represents a significant step toward a better understanding of the cellular elements that contribute to the formation of mature vasculature.S