Anomalia de cromo nas águas subterrâneas de urânia no noroeste do Estado de São Paulo

The existence of chromium in groundwater is a subject of great concern in the northwestera region of the State of São Paulo, where cities depend on groundwater resources for their only source of water. This paper attempts to characterize the areai extent of the chromium anomaly in groundwater in this region; to develop a geochemical study of water, sediments and rocks in the city of Urânia; and to define the relation between public health and the presence of chromium in groundwater for public consumption. Through the combination of data and the systematic study of chromium leveis in water, sediments and rocks, the following conclusions were drawn: the chromium anomaly is not only present in the city of Urânia, but also in other municipalities and districts in northwest São Paulo; the distribution of chromium concentrations is irregular, both in time and space; the source of the chromium is subject to discussion, despite strong evidence that it is natural. However, more in-depth studies are necessary; no relevant conclusions can be drawn about the problems caused by the chromium anomaly to the health of the population served by this water.A ocorrência de cromo nas águas subterrâneas da região noroeste do Estado de São Paulo tem-se configurado como uma grande preocupação, uma vez que as cidades possuem no recurso hídrico subterrâneo a única fonte de água para suprir suas necessidades. Esta pesquisa objetivou caracterizar a extensão da anomalia de cromo nas águas subterrâneas daquela região; desenvolver um estudo geoquímico das águas, sedimentos e rochas da cidade de Urânia; definir a relação saúde pública e a presença de cromo nas águas subterrâneas utilizadas para abastecimento público. Através das análises químicas de águas subterrâneas em localidades do noroeste paulista, feitas no período de 1977 a 1993, pela Companhia Estadual de Saneamento Básico (SABESP), sabe-se que esta anomalia estende-se a outros municípios da região noroeste do Estado. Estudos geoquímicos dos sedimentos da Formação Adamantina e rochas basálticas da Formação Serra Geral da cidade de Urânia mostraram que, enquanto as concentrações de cromo nos primeiros estão acima da média encontrada em sedimentos similares da crosta terrestre, nas rochas basálticas, as concentrações estão abaixo da média dos basaltos da crosta. Um levantamento sobre a saúde da população de Urânia, mostrou que não foi realizado nenhum estudo na região que comprovasse doenças causadas pela ingestão de água contendo cromo acima do limite de potabilidade. Através da integração dos dados e do estudo sistemático dos teores de cromo nas águas, sedimentos e rochas, chegou-se às seguintes conclusões: a anomalia de cromo estende-se além da cidade de Urânia, a outros municípios e distritos do noroeste paulista; a distribuição das concentrações de cromo é irregular, tanto temporal quanto espacialmente; a origem do cromo é discutível, apesar de fortes evidências de ser natural, são necessários estudos mais aprofundados; não se têm conclusões evidentes, se a anomalia de cromo causa problemas à saúde da população abastecida por estas águas

Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients

Elevated plasma lipopolysaccharide (LPS), an indicator of microbial translocation from the gut, is a likely cause of systemic immune activation in chronic HIV infection. LPS induces monocyte activation and trafficking into brain, which are key mechanisms in the pathogenesis of HIV-associated dementia (HAD). To determine whether high LPS levels are associated with increased monocyte activation and HAD, we obtained peripheral blood samples from AIDS patients and examined plasma LPS by Limulus amebocyte lysate (LAL) assay, peripheral blood monocytes by FACS, and soluble markers of monocyte activation by ELISA. Purified monocytes were isolated by FACS sorting, and HIV DNA and RNA levels were quantified by real time PCR. Circulating monocytes expressed high levels of the activation markers CD69 and HLA-DR, and harbored low levels of HIV compared to CD4+ T-cells. High plasma LPS levels were associated with increased plasma sCD14 and LPS-binding protein (LBP) levels, and low endotoxin core antibody levels. LPS levels were higher in HAD patients compared to control groups, and were associated with HAD independently of plasma viral load and CD4 counts. LPS levels were higher in AIDS patients using intravenous heroin and/or ethanol, or with Hepatitis C virus (HCV) co-infection, compared to control groups. These results suggest a role for elevated LPS levels in driving monocyte activation in AIDS, thereby contributing to the pathogenesis of HAD, and provide evidence that cofactors linked to substance abuse and HCV co-infection influence these processes

Modulation of TRAIL resistance in colon carcinoma cells: Different contributions of DR4 and DR5

<p>Abstract</p> <p>Background</p> <p>rhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5). Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether agonistic DR4 or DR5 antibodies could be used to circumvent rhTRAIL resistance, alone or in combination with various chemotherapies.</p> <p>Methods</p> <p>Our study was performed in an isogenic model comprised of the SW948 human colon carcinoma cell line and its rhTRAIL resistant sub-line SW948-TR. Effects of rhTRAIL and agonistic DR4/DR5 antibodies on cell viability were measured using MTT assays and identification of morphological changes characteristic of apoptosis, after acridine orange staining. Sensitivity to the different death receptor ligands was stimulated using pretreatment with the cytokine IFN-gamma and the proteasome inhibitor MG-132. To investigate the mechanisms underlying the changes in rhTRAIL sensitivity, alterations in expression levels of targets of interest were measured by Western blot analysis. Co-immunoprecipitation was used to determine the composition of the death-inducing signalling complex at the cell membrane.</p> <p>Results</p> <p>SW948 cells were sensitive to all three of the DR-targeting agents tested, although the agonistic DR5 antibody induced only weak caspase 8 cleavage and limited apoptosis. Surprisingly, agonistic DR4 and DR5 antibodies induced equivalent DISC formation and caspase 8 cleavage at the level of their individual receptors, suggesting impairment of further caspase 8 processing upon DR5 stimulation. SW948-TR cells were cross-resistant to all DR-targeting agents as a result of decreased caspase 8 expression levels. Caspase 8 protein expression was restored by MG-132 and IFN-gamma pretreatment, which also re-established sensitivity to rhTRAIL and agonistic DR4 antibody in SW948-TR. Surprisingly, MG-132 but not IFN-gamma could also increase DR5-mediated apoptosis in SW948-TR.</p> <p>Conclusions</p> <p>These results highlight a critical difference between DR4- and DR5-mediated apoptotic signaling modulation, with possible implications for future combinatorial regimens.</p

Cytokines as mediators of chemotherapy-associated cognitive changes: Current evidence, limitations and directions for future research

10.1371/journal.pone.0081234PLoS ONE812-POLN