ABSTRACT
Measles is still a major cause of child morbidity and mortality. In recent years, it has become a global public health problem, attributed to low vaccination coverage observed in different countries. In order to control it, a highly effective live virus vaccine is available, which was used for the first time in Chile in 1964, covering practically the whole country in a short period of time. This was the first world experience, which was later imitated by other countries leading to a significant drop in mor bidity and mortality rates. Its effectiveness has been amply demonstrated, but it requires coverage maintenance higher than 95%. In Chile, minor endemic situation persisted until 1993. In recent years, there have been some reduced outbreaks and sporadic cases linked to contacts with imported cases, however, according to recent data, measles is now circulating in more than 160 countries at an unprecedented spread level, where infected travelers are the main vehicle of transmission. In Chile, the Ministry of Health has decided to strengthen and update the vaccination of susceptible groups, especially travelers. This update reviews historical aspects and current information on this re-emer ging disease, showing its high epidemiological impact on the pediatric and adult population globally.
Subject(s)
Disease Outbreaks/prevention & control , Measles Vaccine/administration & dosage , Measles/epidemiology , Adult , Child , Chile/epidemiology , Humans , Measles/prevention & control , Public Health , Vaccination/methodsABSTRACT
Resumen: El sarampión sigue siendo una causa importante de morbilidad y mortalidad en el niño. Durante estos últimos años, se ha convertido en un problema de salud pública mundial, que se atribuye a bajas coberturas de vacunación observadas en diferentes países. Para su control se dispone de una vacuna a virus vivo, altamente eficaz, que fue empleada por primera vez en Chile en 1964, logrando cobertura en prácticamente todo el país en un breve plazo. Esta fue la primera experiencia mundial, imitada lue go por otros países que resulto en una importante caída de las tasas de morbilidad y de mortalidad. Su eficacia ha sido ampliamente demostrada, pero requiere de la mantención de coberturas superiores a 95%. En Chile persistió una situación de endemia de menor magnitud hasta el año 1993. En años recientes, ha habido algunos brotes reducidos y casos esporádicos vinculados a contactos con casos importados, sin embargo, según datos recientes, el sarampión está circulando ahora en más de 160 países en un nivel de propagación sin precedentes, siendo los viajeros infectados el principal vehículo de transmisión. En Chile, el Ministerio de Salud ha decidido reforzar y poner al día la vacunación de grupos susceptibles, en especial viajeros. En esta actualización se revisan aspectos históricos y la información actual de esta enfermedad que ha resurgido mostrando su alto impacto epidemiológico en la población pediátrica y adulta a nivel global.
Abstract: Measles is still a major cause of child morbidity and mortality. In recent years, it has become a global public health problem, attributed to low vaccination coverage observed in different countries. In order to control it, a highly effective live virus vaccine is available, which was used for the first time in Chile in 1964, covering practically the whole country in a short period of time. This was the first world experience, which was later imitated by other countries leading to a significant drop in mor bidity and mortality rates. Its effectiveness has been amply demonstrated, but it requires coverage maintenance higher than 95%. In Chile, minor endemic situation persisted until 1993. In recent years, there have been some reduced outbreaks and sporadic cases linked to contacts with imported cases, however, according to recent data, measles is now circulating in more than 160 countries at an unprecedented spread level, where infected travelers are the main vehicle of transmission. In Chile, the Ministry of Health has decided to strengthen and update the vaccination of susceptible groups, especially travelers. This update reviews historical aspects and current information on this re-emer ging disease, showing its high epidemiological impact on the pediatric and adult population globally.
Subject(s)
Humans , Child , Adult , Measles Vaccine/administration & dosage , Disease Outbreaks/prevention & control , Measles/epidemiology , Chile/epidemiology , Public Health , Vaccination/methods , Measles/prevention & controlABSTRACT
We have recently shown that the adaptor protein p140Cap regulates tumor properties in terms of cell motility and growth. Here, by using the highly metastatic rat adenocarcinoma cell line MTLn3-epidermal growth factor receptor (EGFR), we assess the role of p140Cap in metastasis formation. Orthotopic transplantation of MTLn3-EGFR cells over-expressing p140Cap in Rag2(-/-)γ(c)(-/-) mice resulted in normal primary tumor growth compared with the controls. Strikingly, p140Cap over-expression causes an 80% inhibition in the number of lung metastases. p140Cap over-expressing cells display a 50% reduction in directional cell migration, an increased number and size of focal adhesions, and a strong impairment in the ability to invade in a 3D matrix. p140Cap over-expression affects EGFR signaling and tyrosine phosphorylation of cortactin in response to EGF stimulation. Intriguingly, p140Cap associates with cortactin via interaction with its second proline-rich domain to the cortactin SH3 domain. The phosphomimetic cortactin tyrosine 421 mutant rescues migration and invasive properties in p140Cap over-expressing cells. Taken together, these data demonstrate that p140Cap suppresses the invasive properties of highly metastatic breast carcinoma cells by inhibiting cortactin-dependent cell motility.
Subject(s)
Adaptor Proteins, Vesicular Transport/metabolism , Cortactin/metabolism , Mammary Neoplasms, Experimental/metabolism , Adaptor Proteins, Vesicular Transport/genetics , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Animals , Cell Line, Tumor , Cell Movement , Cortactin/genetics , Epidermal Growth Factor/pharmacology , ErbB Receptors/genetics , ErbB Receptors/metabolism , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , HEK293 Cells , Humans , Immunohistochemistry , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/secondary , Mammary Neoplasms, Experimental/genetics , Mammary Neoplasms, Experimental/pathology , Mice , Mice, Knockout , Microscopy, Fluorescence, Multiphoton , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Transplantation , Phosphorylation/drug effects , Protein Binding , RNA Interference , Rats , Transplantation, HeterologousABSTRACT
Lung cancer is the leading cause of cancer death worldwide. The epidermal growth factor receptor (EGFR) represents the main target for non-small cell lung cancer (NSCLC) therapy, as its overexpression or constitutive activation contributes to malignancy and correlates with poor prognosis. Our previous work demonstrated that in epithelial cells ß1 integrin is required for propagating EGFR signaling from the plasma membrane to the nucleus. In this study, we silenced ß1 integrin in human NSCLC A549 cells. The ß1 integrin-silenced cells show a defective activation of the EGFR signaling cascade, leading to decreased in vitro proliferation, enhanced sensitivity to cisplatin and Gefitinib, impaired migration and invasive behavior. Inhibitory effects on tumor growth and on the EGFR pathway were also observed in in vivo experiments. Moreover, ß1 integrin silencing increases the amount of EGFR on the cell surface, suggesting that ß1 integrin is required for efficient constitutive EGFR turnover at the cell membrane. Although the rate of EGF internalization and recycling is not affected in silenced cells, EGFR signaling is recovered only by expression of the Rab-coupling protein RCP, indicating that ß1 integrin sustains the endocytic machinery required for EGFR signaling. Overall, these results show that ß1 integrin is an essential regulator of EGFR signaling and tumorigenic properties of lung cancer cells, and that its silencing might represent an adjuvant approach to anti-EGFR therapy.
Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/metabolism , Integrin beta1/metabolism , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Adaptor Proteins, Signal Transducing/metabolism , Animals , Antibodies, Monoclonal , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cisplatin/pharmacology , Epidermal Growth Factor/metabolism , Gefitinib , Humans , Integrin beta1/genetics , Lung Neoplasms/drug therapy , Membrane Proteins/metabolism , Mice , Mice, SCID , Neoplasm Invasiveness , Neoplasm Transplantation , Quinazolines/pharmacology , RNA Interference , RNA, Small Interfering , Signal Transduction , Transplantation, HeterologousABSTRACT
Se revisa la epidemiología de la influenza en los últimos años y el brote en curso de influenza aviaria y sus riesgos para el hombre. En el siglo pasado hubo tres pandemias graves de influenza humana causadas por distintos subtipos de virus A que se extendieron por todo el mundo. Según las evidencias clínicas, de laboratorio y epidemiológicas disponibles, existe un riesgo real de una nueva pandemia que eventualmente afectaría al hombre derivada de la epidemia aviaria, A/H5N1, cuyo principal reservorio son aves migratorias. Se inició en Hong Kong en el año 2003 propagándose con gran rapidez a la población avícola en varios países de Asia, Rusia, Macedonia, Colombia y Turquía. Chile no ha sido afectado. La trasmisión ave-hombre está documentada en un número reducido de casos pero se teme que el virus, mediante recombinación genética con cepas humanas, adquiera la capacidad de infectar y trasmitirse al hombre dando curso a su diseminación explosiva. Se discute la estrategia, indicaciones y limitaciones de su prevención y tratamiento incluyendo vigilancia epidemiológica, empleo de fármacos antivirales e inmunización.
Subject(s)
Humans , Child , Adult , Influenza in Birds/epidemiology , Influenza in Birds/transmission , Influenza in Birds/virology , Disease Outbreaks/prevention & control , Disease Transmission, Infectious , Influenza, Human/epidemiology , Influenza, Human/etiology , Influenza A virus/pathogenicity , ZoonosesABSTRACT
We report an experimental approach to separate temperature dependent reversible and irreversible contributions to the perpendicular magnetic anisotropy of Fe films grown at low temperatures on Cu(001) substrates. The surface anisotropy K(S)(T) is found to decrease linearly with temperature, causing a thermally induced spin reorientation into the plane. The irreversible shift of the spin reorientation transition and the coercivity of the iron films are directly correlated to the increasing Fe island size during annealing. The increased coercivity is discussed in terms of domain wall energy inhomogeneities provided by the islands.
Subject(s)
Communicable Disease Control , Communicable Diseases/epidemiology , Vaccines , Chile , Cholera , Diphtheria , Typhoid Fever , Influenza, Human/prevention & control , Poliomyelitis/prevention & control , Rabies , Rubella , Measles , Rubella Syndrome, Congenital , Tuberculosis , Tetanus , ChickenpoxABSTRACT
El efecto inmediato más destacado del programa de vacunación es la notable caída de la tasa de morbilidad y la virtual eliminación de las muertes causadas por sarampión. Persiste, sin embargo, un remanente de casos y continúan ocurriendo brotes esporádicos de magnitud variable. Ha habido, además, como efecto tardío no esperado, un desplazamiento paulatino de las denuncias hacia edades mayores que vaticinan su importancia relativa creciente en el adulto. Los hechos señalados serían consecuencias de la persistencia de "susceptibles residuales" cuyos incrementos periódicos dan origen a brotes cada vez que alcanzan una cifra crítica
