Expressão imuno-histoquímica do cd8, foxp3, Tgf β, tnf α e nf-кb em displasias epiteliais e Carcinomas epidermóides orais

The Oral Epithelial Dysplasia (OED) is the lesion that precedes or co-exists with the Oral Squamous Cell Carcinoma (OSCC), presenting molecular and/or histological similar alterations. The divergences about the malignization potential of OEDs and the role of inflammation in this process make hard the early diagnosis and evaluation of OSCCs aggressiveness. Thus, it became the goal of this study to evaluate the role of inflammation in oral carcinogenesis and tumoral aggressiveness. For this purpose a morphological study was performed in 20 OED cases and 40 OSCC cases to detect the malignization potential of OEDs and the histologic malignancy grading (HMG) of OSCCs, analyzing superficial masses for dismorphism evaluation and the invasive front for evaluation of tumoral growing; and immunohistochemical, using anti-CD8, anti-FOXP3, anti-TGFβ, anti-TNFα and anti-NF-кB antibodies, comparing their with the types lesion, histological degree and intensity of the inflammatory infiltrate. The results were statistically significant for the parameters: cell maturity (p=0,0001), masses presence (p=0,038) and dismorphism (p=0,037), when associated to HMG. To compare the expression of the markers with the types lesion, a significantly higher expression of CD8 (p=0,001) and NF-кB (p=0,002) in the OED, and also a smaller expression of the epithelial TGFβ in the severe OEDs (p=0,011), without significant expression between OSCC degrees. By relating the expression of the studied markers with the inflammatory infiltrate intensity, a positive relation was observed with: inflammatory TNFα(p=0,003), epithelial TNFα and NF-кB (p=0,051 and p=0,004), in OEDs; and with CD8 (p=0,021) and TNFα (p=0,015) in conjunctive OSCCs; and a negative relation with epithelial TNFα (p=0,034) in OSCCs. No significant relation was found between FOXP3 with any of the studied variables. These findings lead to the conclusion that, the study of the invasive front is as important as the study of superficial masses for the evaluation of tumoral aggressiveness; the intensity of the inflammatory infiltrate has no use as a parameter for prognostic evaluation of OSCC in routine exams, but, the molecular events detected in this study may be necessary to give basis for determining the malignant potential in OEDs and aggressiveness in OSCCs

Participação das citocinas Interleucina-12, Interferon-γ, Interleucina-4 e Interleucina-10 e investigação de polimorfismos nos genes do INF-γ (IFNG+874) e da IL-10 (IL10-1082) na malária causada por Plasmodium vivax

A resposta imune na malária é complexa, e os mecanismos de ativação e regulação de linfócitos T efetores e de memória ainda são pouco compreendidos. No presente estudo, determinamos a concentração das citocinas Interferon-γ (IFN-γ), Interleucina-10 (IL-10), Interleucina-4 (IL-4) e Interleucina-12 (IL-12) no soro de indivíduos infectados por Plasmodium vivax, investigamos os polimorfismos no gene do IFN-γ (IFNG+874) e da IL-10 (IL10-1082) e analisamos a associação destes polimorfismos com a concentração das citocinas e com a densidade parasitária. A concentração das citocinas foi determinada por ELISA, e a genotipagem dos polimorfismos IFNG+874 e IL10-1082 foi realizada pelas técnicas de ASO-PCR e PCR-RFLP, respectivamente. Os indivíduos infectados apresentaram níveis séricos de IFN-γ e IL-10 aumentados. A produção de IFN-γ foi maior nos indivíduos primoinfectados, porém não foi associada com a redução da parasitemia. A produção de IL-10 foi alta e associada com altas parasitemias. As citocinas IL-4 e IL-12 não foram detectadas. As freqüências dos genótipos homozigoto mutante AA, heterozigoto AT e selvagem TT do gene do IFN-γ foram 0,51, 0,39 e 0,10, respectivamente. As freqüências dos genótipos homozigoto mutante AA, heterozigoto AG e selvagem GG para IL10 foram 0,49, 0,43 e 0,08, respectivamente. Apenas o polimorfismo do IFN-γ foi associado com níveis reduzidos desta citocina. Na malária causada por P. vivax, houve produção de citocina que caracteriza o perfil Th1 (IFN-γ), com possível participação da IL-10 na imunorregulação.

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 1082 - Bericht über den Beginn der Drucklegung der Schopenhauer-Publikation im Verlag Rudolf Kuntze

u.a. Naturwissenschaft;

Pliocene-Pleistocene alkenone, nitrogen and opal record of ODP Site 175-1082

In this study we present combined high-resolution records of sea surface temperature (SST), phytoplankton productivity, and nutrient cycling in the Benguela Upwelling System (BUS) for the past 3.5 Ma. The SST record provided evidence that upwelling activity off Namibia mainly intensified ca. 2.4-2.0 Ma ago in response to the cooling of the Southern Ocean and the resultant strengthening of trade winds. As revealed by productivity-related proxies, BUS intensification led to a major transition in regional biological productivity when considering the termination of the Matuyama Diatom Maximum (a diatom high-production event). Major oceanic reorganization in the Benguela was accompanied by nutrient source changes, as indicated by a new nitrogen isotopic (delta15N) record that revealed a stepwise increase at ca. 2.4 and ca. 1.5 Ma ago. The change in source region likely resulted from significant changes in intermediate water formation tied to the reorganization of oceanic conditions in the Southern Ocean, which may have in turn mainly controlled the global ocean N cycle, and therefore the N isotopic composition of nutrients since 3.5 Ma ago.

(Table 2) Age interval and accumulation rates of organic and inorganic carbon from ODP Sites 175-1082, 175-1084, 175-1085 and 175-1087

The Ocean Drilling Program Leg 175 recovered a unique series of stratigraphically continuous sedimentary sections along the SW African margin, an area which is presently affected by active coastal upwelling. The accumulation rates of organic and inorganic carbon are a major component of this record. Four Leg 175 sites (1082, 1084, 1085, 1087) are chosen as part of a latitudinal transect from the present northern to southern boundaries of the Benguela Current upwelling system, to decipher the Pliocene-Pleistocene history of biogenic production and its relationship with global and local changes in oceanic circulation and climate. The pattern of CaCO3 and Corg mass accumulation rates (MARs) over 0.25-Myr intervals indicates that the evolution of carbon burial is highly variable between the northern and the southern Benguela regions, as well as between sites that have similar hydrological conditions. This, as well as the presence over most locations of high-amplitude, rapid changes of carbon burial, reflect the partitioning of biogenic production and patterns of sedimentation into local compartments over the Benguela margin. The combined mapping of CaCO3 and Corg MARs at the study locations suggests four distinct evolutionary periods, which are essentially linked with major steps in global climate change: the early Pliocene, the mid-Pliocene warm event, a late Pliocene intensification of northern hemisphere glaciation and the Pleistocene. The early Pliocene spatially heterogeneous patterns of carbon burial are thought to reflect the occurrence of mass-gravitational movements over the Benguela slope which resulted in disruption of the recorded biogenic production. This was followed (3.5-3 Ma) by an episode of peak carbonate accumulation over the whole margin and, subsequently, by the onset of Benguela provincialism into a northern and a southern sedimentary regime near 2 Ma. This mid and late Pliocene evolution is interpreted as a direct response to changes in the ventilation of bottom and intermediate waters, as well as to dynamics of the subtropical gyral circulation and associated wind stress.