Association of TNF-alpha genetic variants with HPV-associated oral cancer risk---a case-control study

The incidence of OSCC in younger population and in those who never smoked or drank has increased since the last decade. This increase may be attributable to increase of infection with HPV. The pro-inflammatory cytokine TNF-&agr; has the role in the pathogenesis of chronic inflammatory diseases and was found to control HPV infection in cervical cancer studies. Our study aimed to investigate the association between the four polymorphisms located in TNF-&agr; promoter region, -308(rs1800629), -857(rs1799724), -863(rs1800630) and -1031(rs1799964), and the risk of HPV-related OSCC. In this hospital-based case-control study, 325 cases and 335 controls were included. We found that HPV 16 seropositivity was associated with an increased risk of oral cancer (OR = 3.1, 95% CI, 2.1–4.6). Each of the polymorphism showed to increase the risk of HPV-related OSCC. And after combining the risk genotypes and using the low-risk group (0–1 combined risk genotypes) and HPV16 seronegativity as the reference group, only the high-risk groups (3–4 combined risk genotypes) and HPV16 seronegativity were associated with a low OR of 1.8 (95% CI, 1.1–2.8), while the low-risk and high-risk groups and HPV16 seropositivity were significantly associated with a higher OR of 2.7 (95% CI, 1.3–5.8) and 8.5 (95% CI, 3.7–19.4), respectively. In addition, the joint effects were greater among the young subjects (aged<50), males, never smokers or never drinkers, and patients with oropharyngeal cancer. Overall, the four TNF-&agr; polymorphisms, individually or collectively, would result in a significantly increased risk for HPV16-associated oral cancer in a non-Hispanic white population. More large sized studies are needed for future investigation.^

Design, synthesis and cellular and molecular pharmacology of 2$\sp\prime$-bromo-4$\sp\prime$-epidaunorubicin (WP401): A novel non-cross-resistant anthracycline antibiotic with the intrinsic ability to circumvent P -glycoprotein-mediated drug resistance

We designed and synthesized a novel daunorubicin (DNR) analogue that effectively circumvents P-glycoprotein (P-gp)-mediated drug resistance. The fully protected carbohydrate intermediate 1,2-dibromoacosamine was prepared from acosamine and effectively coupled to daunomycinone in high yield. Deprotection under alkaline conditions yielded 2$\sp\prime$-bromo-4$\sp\prime$-epidaunorubicin (WP401). The in vitro cytotoxicity and cellular and molecular pharmacology of WP401 were compared with those of DNR in a panel of wild-type cell lines (KB-3-1, P388S, and HL60S) and their multidrug-resistant (MDR) counterparts (KB-V1, P388/DOX, and HL60/DOX). Fluorescent spectrophotometry, flow cytometry, and confocal laser scanning microscopy were used to measure intracellular accumulation, retention, and subcellular distribution of these agents. All MDR cell lines exhibited reduced DNR uptake that was restored, upon incubation with either verapamil (VER) or cyclosporin A (CSA), to the level found in sensitive cell lines. In contrast, the uptake of WP401 was essentially the same in the absence or presence of VER or CSA in all tested cell lines. The in vitro cytotoxicity of WP401 was similar to that of DNR in the sensitive cell lines but significantly higher in resistant cell lines (resistance index (RI) of 2-6 for WP401 vs 75-85 for DNR). To ascertain whether drug-mediated cytotoxicity and retention were accompanied by DNA strand breaks, DNA single- and double-strand breaks were assessed by alkaline elution. High levels of such breaks were obtained using 0.1-2 $\mu$g/mL of WP401 in both sensitive and resistant cells. In contrast, DNR caused strand breaks only in sensitive cells and not much in resistant cells. We also compared drug-induced DNA fragmentation similar to that induced by DNR. However, in P-gp-positive cells, WP401 induced 2- to 5-fold more DNA fragmentation than DNR. This increased DNA strand breakage by WP401 was correlated with its increased uptake and cytotoxicity in these cell lines. Overall these results indicate that WP401 is more cytotoxic than DNR in MDR cells and that this phenomenon might be related to the reduced basicity of the amino group and increased lipophilicity of WP401. ^

Subprograma de salud bucal "El hospital y los chicos" : del diagnóstico del estado dental a la priorización de programas necesarios

Los objetivos de este trabajo fueron determinar el estado dental de la población bajo estudio, detectar subgrupos de riesgo específico para enfermedades bucales y proponer estrategias de intervención apropiadas para la promoción de la salud bucal para ellos. Método: sobre la base de datos del subprograma de salud bucal "El hospital y los chicos" se efectuó un estudio descriptivo del estado dental sobre 277 niños entre 2 meses y 13 años de edad asistentes al CDlF Nº11, Guaymallén, Mendoza. Se registraron: ceod, CPOD, ceos CPOS, índice de Necesidad de tratamiento de caries, índice de Paca de Silness y Loe, ICDAS II, y datos demográficos. Además, como parte del programa, se llevó a cabo la enseñanza de Técnicas de Higiene Bucal adecuada a la edad, dirigidas a madres y niños, y una topicación de flúor profesional siguiendo protocolos específicos según edad del niño. Resultados: la población libre de caries fue del 31,4%, mientras que el 68,6% tuvo experiencia de caries pasada o presente. La media de la sumatoria de ceod+ cpod fue 4,91 = 5, con una carga de enfermedad muy alta denotada por un componente c+C de 4.25=4.55. Presentó un valor para ceos+CPOS de 9,22+11 96 y de c+CS de 6.8918 61. En cuanto a la severidad de las lesiones de caries expresadas con las categorías de ICDAS II del 2 al 6, se observó que las medias mayores corres- , ponden al nivel 6 (x2 Friedman= 20,999, p= 0,000). La media de necesidad de tratamiento de caries fue de 5,74, pero los niveles 8 y más abarcan al 33.2% de la población de estudio Se observó un aumento progresivo de estos indicadores en la primera infancia comenzando en la primera franja etaria con una media de ceod+CPOD de 0.8811,92, de 3, 93t4.65a los tres años, de 6,38+6,36 a los 5 años, y de 8,40+5,47 a los 7 años, siendo esta población la que presentó el mayor valor del indicador (x2 Kruskall Wallis= 104,637, p=O,OO). El índice CPOD fue de 1,35~1,34 a los 7 años y de 4.65+3 99 a los 9 ( x2 Kruskall Wallis =17,609 y p=0,001) Conclusiones~ este grupo de niños de alto riesgo social presentó elevados índices de caries y de necesidad de tratamiento, que requerirán de un sistema de salud que pueda contenerlos. Al observar las medias de ceod+CPOD según las categorías de edad se pone de manifiesto una tendencia a agravarse el estado dentario en la primera infancia, llegando a valores muy por encima de la media general para los 5, 6 ,7 y 8 años El CEOD también tiende a aumentar con la edad, poniendo en evidencia la susceptibilidad de caries de los molares permanentes erupcionados Las tendencias de los indicadores permitieron reconocer dos subgrupos de riesgo para desarrollar programas preventivos' el de niños de O a 3 años, y el de 6 a 12, es decir niños escolares. Se sugieren dos programas prioritarios Materno- infantil y Protección de 1er molar permanente.

Velocities and elastic moduli of basalts from Pacific DSDP sites

Compressional (Vp) and shear (Vs) wave velocities have been measured to 10 kb in 32 cores of basalt from 14 Pacific sites of the Deep Sea Drilling Project. Both Vp and V s show wide ranges (3.70 to 6.38 km/sec for Vp and 1.77 to 3.40 km/sec for V s at 0.5 kb) which are linearly related to density and sea floor age, confirming earlier findings by Christensen and Salisbury of decreasing velocity with progressive submarine weathering based on studies of basalts from five sites in the Atlantic. Combined Pacific and Atlantic data give rates of decreasing velocity of -1.89 and -1.35 km/sec per 100 my for Vp and Vs respectively. New analyses of oceanic seismic refraction data indicate a decrease in layer 2 velocities with age similar to that observed in the laboratory, suggesting that weathering penetrates to several hundred meters in many regions and is largely responsible for the extreme range and variability of layer 2 refraction velocities.

Composite depth scale, tie points and magnetic susceptibilities of ODP Site 178-1098 sediments

Multiple holes were cored at Ocean Drilling Program Leg 178 Sites 1098 and 1099 in two subbasins of the Palmer Deep in order to recover complete and continuous records of sedimentation. By correlating measured properties of cores from different holes at a site, we have established a common depth scale, referred to as the meters composite depth scale (mcd), for all cores from Site 1098. For Site 1098, distinct similarities in the magnetic susceptibility records obtained from three holes provide tight constraints on between-hole correlation. Additional constraints come from lithologic features. Specific intervals from other data sets, particularly gamma-ray attenuation bulk density, magnetic intensity, and color reflectance, contain distinctive anomalies that correlate well when placed into the preferred composite depth scale, confirming that the scale is accurate. Coring in two holes at Site 1099 provides only a few meters of overlap. None of the data sets within this limited overlap region provide convincing correlations. Thus, the preferred composite depth scale for Site 1099 is the existing depth scale in meters below seafloor (mbsf).

Políticas y planes de lectura : El caso de Uruguay

Se aborda el tema de las políticas públicas de promoción de la lectura, enfatizando en la formulación de planes nacionales, como medio para implementar dichas políticas en el contexto socio-educativo de un país. Se hace una breve referencia a las acciones a favor de la lectura en Iberoamérica y se estudia particularmente la situación de Uruguay con especial referencia al Plan Nacional de Lectura. Se esbozan los conceptos de campaña de lectura, promoción de la lectura, animación a la lectura y políticas públicas de lectura. Se reflexiona sobre la importancia de la lectura en el nuevo contexto social pautado por la fuerte presencia de las tecnologías de la información y la comunicación. Se enfatiza en la importancia de la lectura textual y multimedial (recreativa, educativa, informativa) como herramienta fundamental para la formación de individuos críticos que puedan ser capaces de desarrollar competencias para la sociedad del siglo XXI