Ursolic acid: A novel antiviral compound inhibiting rotavirus infection in vitro.

Rotavirus is one of the leading causes of severe acute gastroenteritis in children under 5 years of age, mainly affecting developing countries. Once the disease is acquired, no specific treatment is available; as such, the development of new drugs for effective antirotaviral treatment is critical. Ursolic acid is a pentacyclic triterpenoid with antiviral activity, which has been studied extensively in vitro and in vivo. To study the potential antirotaviral activity of ursolic acid, its toxic potential for viral particles (virucidal effect) and cultured cells (cytotoxicity) was analysed. No effect on virion infectivity was observed with treatments of up to 40 µM ursolic acid, while incipient cytotoxicity started to be evident with 20 µM ursolic acid. The antiviral potential of ursolic acid was evaluated in in-vitro rotavirus infections, demonstrating that 10 µM ursolic acid inhibits rotavirus replication (observed by a decrease in viral titre and the level of the main viral proteins) and affects viral particle maturation (a process associated with the endoplasmic reticulum) 15 h post infection. Interestingly, ursolic acid was also found to hamper the early stages of the viral replication cycle, as a significant reduction in the number and size of viroplasms, consistent with a decrease in VP6 and NSP2 viral proteins, was observed 4 h post infection. As such, these observations demonstrate that ursolic acid exhibits antiviral activity, suggesting that this chemical could be used as a new treatment for rotavirus.

Site-bond percolation of heteronuclear dimers irreversibly deposited on square lattices.

A generalization of the site-bond percolation problem was studied, in which pairs of neighboring sites (site dimers) and bonds are occupied irreversibly, randomly, and independently on homogeneous square surfaces. A dimer is composed of two segments and occupies two adjacent sites. Each segment can be either a conductive segment (segment type A) or a nonconductive segment (segment type B). Two types of dimers are considered, AA and AB, and the connectivity analysis is carried out by accounting only for the conductive segments (segments type A) in combination with bonds. For the combination of dimers and bonds, two different criteria were analyzed: the union or the intersection between the adsorbed percolating particles and the bonds. By means of numerical simulations and finite-size scaling analysis, the complete phase diagram separating a percolating from a non-percolating region was determined.

Percolation of heteronuclear dimers irreversibly deposited on square lattices.

The percolation problem of irreversibly deposited heteronuclear dimers on square lattices is studied. A dimer is composed of two segments, and it occupies two adjacent adsorption sites. Each segment can be either a conductive segment (segment type A) or a nonconductive segment (segment type B). Three types of dimers are considered: AA, BB, and AB. The connectivity analysis is carried out by accounting only for the conductive segments (segments type A). The model offers a simplified representation of the problem of percolation of defective (nonideal) particles, where the presence of defects in the system is simulated by introducing a mixture of conductive and nonconductive segments. Different cases were investigated, according to the sequence of deposition of the particles, the types of dimers involved in the process, and the degree of alignment of the deposited objects. By means of numerical simulations and finite-size scaling analysis, the complete phase diagram separating a percolating from a nonpercolating region was determined for each case. Finally, the consistency of our results was examined by comparing with previous data in the literature for linear k-mers (particles occupying k adjacent sites) with defects.

Surface order-disorder phase transitions and percolation.

In the present paper, the connection between surface order-disorder phase transitions and the percolating properties of the adsorbed phase has been studied. For this purpose, four lattice-gas models in the presence of repulsive interactions have been considered. Namely, monomers on honeycomb, square, and triangular lattices, and dimers (particles occupying two adjacent adsorption sites) on square substrates. By using Monte Carlo simulation and finite-size scaling analysis, we obtain the percolation threshold theta(c) of the adlayer, which presents an interesting dependence with w/k(B)T (w, k(B), and T being the lateral interaction energy, the Boltzmann constant, and the temperature, respectively). For each geometry and adsorbate size, a phase diagram separating a percolating and a nonpercolating region is determined.

Toxicidad aguda de altas dosis de metotrexato en el tratamiento de leucemia linfoblástica aguda en niños / Acute toxicity of high close of Methotrexae in children with acute lymphoblastic leukemia

El objetivo de ese estudio fue evaluar y comparar la aparición de efectos adversos agudos luego de la infusión de metotrexato (MTX), citostático incluido en alas dosis en 2 diferentes protocolos (2g. vs. 5g/m2 por ciclo), utilizados durante la fase M del tratamiento de las leucemias linfoblásticas agudas (LLA) en el paciente pediátrico. Sesenta y seis pacientes que recibieron 264 ciclos de quimioterapia con altas dosis de MTX, fueron estudiados entre enero de 1995 y febrero de 1997. Todos ellos tenían el diagnóstico de LLA de riesgo estándar e intermedio, estaban en remisión completa y habián recibido anteriormente el protocolo I. Se anlizaron 2 tratamiento: el gurpo A) 132 ciclos con MTX a razón de 2g/m2/ciclo (n=32); grupo B 136 cilos con MTX a razón de 5g/m2/ciclo (n=34). Todos los pacientes recibieron 4 infusiones de MTX (1/10 de la dosis en 30´ y 9/10 de la dosis en el resto de las 24 hs.), con hidratación a 3000 ml/m2/día y alcalinización urinaria, en forma bimensual, junto a una punción lumbar con mediación intratecal (Profilaxis para evitar compromiso del sistema nervioso central) y 6-mercaptopurina oral diariamente durante el ciclo. No se observaron diferencias estadísticas significativas en relación a toxicidad hematológica severa: en 42 cukis (32.81 por ciento) en el grupo A y 44 cilcos (32.35 por ciento) en el grupo B; z=0.042: p=0.967. Sin embargo, la aparición de mucositis moderada y severa y valores elevados de las enzimas hepáticas se observaron con mayor frecuencia en el grupo B, mostrando una diferencia estadísticamente significativa. En nuestro estudio, no se observaron valores anormales de creatinina sérica. No hubo impacto sobre variaciones en el peso corporal en ambos protocolos. Concluimos que la dosis de MTX no influyó sobre la aparición de toxicidad hematológica, pero si sobre la aparición de efectos adversos en el tracto gastrointestinal y la función hepática.