¿Es posible curar la infección por VIH? / Is it possible to cure HIV infection?

El tratamiento antirretroviral ha logrado normalizar las expectativas de vida de las personas infectadas por VIH, pero no logra la curación de la enfermedad. Se han identificado obstáculos que impiden la curación con solo tratamiento antirretroviral, que incluyen la existencia de un reservorio de células latentemente infectadas, la replicación vírica persistente en tejidos y los santuarios anatómicos. Se persigue como principal estrategia de curación la administración de fármacos que reactiven el virus latente para de este modo eliminar el reservorio celular. Los ensayos clínicos en marcha han mostrado la prueba de concepto, pero aún no se ha demostrado la eficacia de estos fármacos en disminuir el tamaño del reservorio (AU)

Antiretroviral therapy has significantly improved the life expectancy in HIV-infected people, but it cannot cure the disease by itself. Several barriers have been identified for the cure of HIV infection, including a reservoir of latently infected cells, persistent viral replication in tissues, and anatomical sanctuaries. The main strategy proposed for the cure of HIV consists on the administration of drugs that, through the reactivation of latent HIV, would eliminate the cell reservoir. Ongoing clinical trials have shown the proof of concept, but the efficacy of these drugs in decreasing the reservoir size has not been proved so far (AU)

Measuring human mast cell-mediated cytotoxicity against human tumour cells: three-colour flow cytometry using monoclonal antibody target staining with annexin V / propidium iodide co-labelling of death

Background: Chromium release assay is the standard method for evaluation of cell-mediated cytotoxicity, including that of mast cells. Although this is a reproducible method, it has more drawbacks than even radioactivity. In addition to the shortcoming of measuring only necrotic killing, some non-radioactive methods have not been widely used either. The numerous limitations of these methods led researchers to develop other techniques. This study describes a new flow cytometric approach that measures human mast cell-mediated cytotoxicity by marking target cells with monoclonal antibody alongside annexin V/ PI co-labelling. Methods: A colony forming unit - mast in vitro was developed from human bone marrow mononuclear cells in serum-free methylcellulose medium. Six-week-old human bone marrow-derived mast cells were used as effectors, and malignant B-lymphoblastoid cell lines like Daudi / Raji cells as targets. Effectors and targets were both co-incubated for short and long-term durations, and experiments were repeated several times. Cytotoxicity was calculated by flow cytometric mast cell-mediated cytotoxicity assay. Results: This method was able to clearly show mast cell-mediated cytotoxicity against human tumours. It is well-known that some lymphokine-activated killer-sensitive cells are resistant to mast cell-mediated cytotoxicity. However, a different type of lymphokine activated killer-sensitive cell in this study was found to be very sensitive to mast cell-mediated cytotoxicity. Moreover, this technique also allowed us to separate killing into different stages: early and late apoptosis. Conclusions: When compared to chromium release and non-radioactive methods, this method has the advantages of allowing evaluation of early apoptosis and short/long term mast cell-mediated cytotoxicity with specific target marking(AU)

Dynamics and kinetics of natural killer cell cytotoxicity in human malaria as evaluated by a novel stepwise cytotoxicity assay

Malaria causes important functional alterations of the immune system, but several of them are poorly defined. To evaluate thoroughly the natural killer cell cytotoxicity in patients with malaria, we developed a technique capable to assess both the dynamics and the kinetics of the process. For the kinetics assay, human peripheral blood mononuclear cells were previously incubated with K562 cells and kept in agarose medium, while for the dynamics assay both cells were maintained in suspension. NK activity from patients with vivax malaria presented a kinetics profile faster than those with falciparum malaria. NK cytotoxicity positively correlated with parasitemia in falciparum malaria. The dynamics of NK cytotoxicity of healthy individuals was elevated at the beginning of the process and then significantly decreased. In contrast, malaria patients presented successive peaks of NK activity. Our results confirmed the occurrence of alteration in NK cell function during malaria, and added new data about the NK cytotoxicity process.

A malária causa importantes alterações do sistema imunitário, muitas ainda mal definidas. Para permitir uma avaliação abrangente da atividade citotóxica das células natural killer em pacientes com malária, desenvolvemos um teste capaz de avaliar concomitantemente a dinâmica e a cinética do processo. Para a avaliação da cinética, células mononucleares do sangue periférico interagiram com células K562 e foram mantidas em agarose, enquanto para avaliar a dinâmica as células eram mantidas em suspensão. A cinética da atividade citotóxica das células NK foi mais rápida em pacientes com Plasmodium vivax, do que naqueles infectados com P. falciparum. Nestes, houve correlação positiva entre a atividade citotóxica das células NK e a parasitemia. O padrão da dinâmica da atividade citotóxica nos pacientes com malária foi bem diferente daquele apresentado pelos indivíduos sadios. Enquanto nestes, a atividade estava muito aumentada no início da incubação das células, sofrendo posteriormente uma redução, nos indivíduos infectados foram detectados sucessivos picos de atividade citotóxica. Nossos resultados confirmam a ocorrência de alteração funcional das células NK na malária humana e acrescentam novos dados sobre a dinâmica e a cinética da atividade citotóxica.

Poria cocos, un hongo con propiedades antiinflamatorias e inmunoestimulantes / Poria cocos, a fungus with anti-inflammatory and immunoestimulant properties

El esclerocio de Poria cocos (Schw.) Wolf (Poliporáceas) denominado "fu-ling" (China) o "hoelen" (Japón) es una de las drogas más apreciadas en las medicinas tradicionales orientales por sus propiedades diuréticas, sedantes y tónicas. Se trata de un hongo saprofítico que crece sobre diferentes especies de Pinus, y cuyos principios activos más relevantes son los polisacáridos y los triterpenoides, los cuales han sido el principal objetivo de los estudios farmacológicos. De ellos, los triterpenos destacan por sus propiedades antiinflamatorias y los polisacáridos como inmunoestimulantes, mientras que en las propiedades citotóxicas están implicados ambos tipos de principios. Sin embargo, el número de ensayos clínicos realizados, para establecer su eficacia y seguridad, es limitado. En esta revisión se han recopilado todos los datos sobre química y farmacología de Poria cocos, con el fin de establecer su interés clínico para futuros empleos en patologías donde la inflamación y el sistema inmunológico estén implicados (AU)

The screrotium of Poria cocos (Schw.) Wolf (Polyporaceae), also called "fu-ling" (China) or "hoelen" (Japan), is a wellknown traditional Asian medicine used for its diuretic, sedative, and tonic effects. It is a saprophytic fungus growing in diverse species of Pinus. Polysaccharides and triterpenoids, the two relevant groups of phytochemicals present in Poria cocos, have been the principal subjects of pharmacological studies on this fungus. Whereas triterpenes exhibit marked anti-inflammatory activity, polysaccharides have immunostimulant effects, but both groups have been shown to possess anticancer properties. Unfortunately, the amount of published research on the clinical properties of Poria cocos is insufficient to establish its efficacy and safety from a scientific point of view. In this review we have compiled all the data on the plant’s chemistry and pharmacology in order to determine its clinical interest for future use in various pathologies in which inflammation and immunodepression are implicated (AU)

Os escleródios de Poria cocos (Schw.) Wolf (Polyporaceae) chamado "fu-ling" (China) ou "hoelen" (Japão) é uma das drogas mais populares na medicina oriental tradicional para a sua diurética, sedativa e tônica. É um fungo saprófita que cresce em várias espécies de Pinus, e cujos princípios são polissacarídeos e triterpenos, que têm sido o principal objetivo dos estudos farmacológicos. Destes, os triterpenos são conhecidos por suas propriedades antiinflamatórias e polissacarídeos como imunoestimulante, enquanto as propriedades citotóxicas envolvendo ambos os tipos de princípios activos. No entanto, o número de ensaios clínicos para determinar sua segurança e eficácia é limitada. Nesta revisão, reunimos todos os dados sobre a química e farmacologia de Poria cocos, a fim de estabelecer a sua relevância clínica para os trabalhos futuros em doenças onde a inflamação eo sistema imunológico estão envolvidos (AU)

Participación de la apoptosis en los procesos inmunológicos / Participation of apoptosis in immunologic processes

Apoptosis is a biological process that leads certain cells to die in a controlled fashion. Its biochemical manifestation is DNA fragmentation due to the action of an endonuclease and morphological consequences is the formation of apoptic bodies, seen with lught or electron microscopy. Apoptosis is universally important in embryogenesis and morphologenesis of all tissues. Lately, a fundamental role of apoptosis in the physiology and physiopathology of immunological events has been uncovered. This review details the role of apoptosis in the development of auto-tolerance, immunological memory and AIDS pathogenesis

Citolisis natural en sujetos infectados por VIH-I: alteración de la activación de las células natural killer / Natural cytolysis in HIV-1 infected individuals: alteration in the activation of the natural killer cells

Las células Natural Killer (cél NK), linfocitos efectores de actividad citolítica natural, son críticas en la defensa antiinfecciosa. En la infección por VIH-I se ha descrito una disminución de la actividad citolítica NK; sin embargo, se desconocen los mecanismos involucrados, por lo que el objetivo de este trabajo fue estudiar la ACNK y la acción in vitro de inmunomoduladores para intentar explicar esta deficiencia. Se analizaron 20 individuos infectados por VIH-I (10 asintomáticos y 10 con SIDA) y 30 individuos seronegativos como controles. La ACNK se determinó utilizando cél K-562 radiomarcadas con 51-Cr (cromato de sodio) como cél blanco y cél mononucleares periféricas como cél efectoras, expresándose los resultados como por ciento de Lisis específica. En cultivos in vitro, se analizó el efecto de inmunomoduladores sobre la ACNK: interleuquina-2 (IL-2, 25 U/mL), interferon-alfa (IFN-a, 500 U/mL) y la acción conjunta de ionófor de calcio A23187 (lo, 10.0 uM) más un éster de forbol (TPA, 250 ng/mL)(Io+TPA). El análisis fenotípico, CD 16+/56+ se efectuó por citometría de flujo con Ac monoclonales fluorescentes (Becton Dickinson)

El desarrollo inmunitario y su influencia sobre las particularidades de las infecciones en el niño / Development of antiinfectious defense and its influence on the characteristics of infections in the child

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