74 research outputs found

    RISCO DE DOENÇA TROMBOLÍTICAS APÓS O USO DE ALGESTONA ACETOFENIDA E ENANTATO DE ESTRADIOL

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    Muitos estudos tem demonstrado que há um risco acentuado de doenças trombolíticas, que podem ser agravadas com predisposições a obesidade, fatores genéticos, fumantes e entre outros. No entanto, estes riscos não são, normalmente citados antes do uso métodos contraceptivos hormonais. Sendo assim, muitas mulheres estão expostas a riscos graves a saúde durante o uso de contraceptivos hormonais. Logo, o intuito do nosso estudo foi avaliar uso prolongado da substância algestona acetofenida e enantato de estradiol sobre o ciclo menstrual de fêmeas cativas de Sapajus libidinosus (macaco-prego). Para tal, foram usadas 06 fêmeas adultas de macaco-prego mantidas no Centro de Primatologia da Universidade de Brasília CP/UnB. Para fins experimentais, as fêmeas receberam uma dose única de 0,10 ml do contraceptivo injetável, que foi administrado a cada 21 dias. Sendo assim, cada fêmea recebeu 05 administrações de contraceptivo consecutivas. Também foram realizadas 12 coletas de sanguíneas de cada fêmea, por meio deste material biológico foram analisados os fatores de coagulação sanguínea, por exemplos, número de plaquetas, fibrinogênio e tempos de protrombina (TP) e tromboplastina (TTPa). Os resultados obtidos permitiram identificar que houve alterações nos fatores de coagulação sanguínea, pois foi registrado um aumento no número de plaquetas (F1,61=450.92; p<0.05) e redução nos tempos de TP (F1,61=91.77; p<0.001) e TTPa (F1,61=42.94; p<0.001). Diante disso é possível mencionar que o contraceptivo administrado nas fêmeas de macaco-prego promoveu alterações nos parâmetros fisiológicos, que são relacionados nos fatores de coagulação. Neste sentido, as fêmeas de macaco-prego podem ser um modelo animal importante, para estudos sobre o tema na medida em que os resultados aqui obtidos demonstram que, fisiologicamente, elas apresentam alterações semelhantes àquelas, que também são encontradas nas mulheres usuárias de contraceptivo hormonal combinado

    Phylogenetic Analysis of the Neks Reveals Early Diversification of Ciliary-Cell Cycle Kinases

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    NIMA-related kinases (Neks) have been studied in diverse eukaryotes, including the fungus Aspergillus and the ciliate Tetrahymena. In the former, a single Nek plays an essential role in cell cycle regulation; in the latter, which has more than 30 Neks in its genome, multiple Neks regulate ciliary length. Mammalian genomes encode an intermediate number of Neks, several of which are reported to play roles in cell cycle regulation and/or localize to centrosomes. Previously, we reported that organisms with cilia typically have more Neks than organisms without cilia, but were unable to establish the evolutionary history of the gene family

    Initiation of human colon cancer cell proliferation by trypsin acting at protease-activated receptor-2

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    The protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved and activated by trypsin. We investigated the expression of PAR-2 and the role of trypsin in cell proliferation in human colon cancer cell lines. A total of 10 cell lines were tested for expression of PAR-2 mRNA by Northern blot and RT-PCR. PAR-2 protein was detected by immunofluorescence. Trypsin and the peptide agonist SLIGKV (AP2) were tested for their ability to induce calcium mobilization and to promote cell proliferation on serum-deprived cells. PAR-2 mRNA was detected by Northern blot analysis in 6 out of 10 cell lines [HT-29, Cl.19A, Caco-2, SW480, HCT-8 and T84]. Other cell lines expressed low levels of transcripts, which were detected only by RT-PCR. Further results were obtained with HT-29 cells: (1) PAR-2 protein is expressed at the cell surface; (2) an increase in intracellular calcium concentration was observed upon trypsin (1–100 nM) or AP2 (10–100 μM) challenges; (3) cells grown in serum-deprived media supplemented with trypsin (0.1–1 nM) or AP2 (1–300 μM) exhibited important mitogenic responses (3-fold increase of cell number). Proliferative effects of trypsin or AP2 were also observed in other cell lines expressing PAR-2. These data show that subnanomolar concentrations of trypsin, acting at PAR-2, promoted the proliferation of human colon cancer cells. The results of this study indicate that trypsin could be considered as a growth factor and unravel a new mechanism whereby serine proteases control colon tumours. © 2001 Cancer Research Campaign http://www.bjcancer.co

    Integrative approach for differentially overexpressed genes in gastric cancer by combining large-scale gene expression profiling and network analysis

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    Gene expression profiling is a valuable tool for identifying differentially expressed genes in studies of disease subtype and patient outcome for various cancers. However, it remains difficult to assign biological significance to the vast number of genes. There is an increasing awareness of gene expression profile as an important part of the contextual molecular network at play in complex biological processes such as cancer initiation and progression. This study analysed the transcriptional profiles commonly activated at different stages of gastric cancers using an integrated approach combining gene expression profiling of 222 human tissues and gene regulatory dynamic mapping. We focused on an inferred core network with CDKN1A (p21WAF1/CIP1) as the hub, and extracted seven candidates for gastric carcinogenesis (MMP7, SPARC, SOD2, INHBA, IGFBP7, NEK6, LUM). They were classified into two groups based on the correlation between expression level and stage. The seven genes were commonly activated and their expression levels tended to increase as disease progressed. NEK6 and INHBA are particularly promising candidate genes overexpressed at the protein level, as confirmed by immunohistochemistry and western blotting. This integrated approach could help to identify candidate players in gastric carcinogenesis and progression. These genes are potential markers of gastric cancer regardless of stage

    Protease Activated Receptor Signaling Is Required for African Trypanosome Traversal of Human Brain Microvascular Endothelial Cells

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    Human African trypanosomiasis, or sleeping sickness, occurs when single-cell trypanosome protozoan parasites spread from the blood to brain over the blood-brain barrier (BBB). This barrier is composed of brain microvascular endothelial cells (BMECs) especially designed to keep pathogens out. Safe drugs for treating sleeping sickness are lacking and alternative treatments are urgently required. Using our human BMEC BBB model, we previously found that a parasite protease, brucipain, induced calcium activation signals that allowed this barrier to open up to parasite crossing. Because human BMECs express protease-activated receptors (PARs) that trigger calcium signals in BMECs, we hypothesized a functional link between parasite brucipain and BMEC PARs. Utilizing RNA interference to block the production of one type of PAR called PAR-2, we hindered the ability of trypanosomes to both open up and cross human BMECs. Using gene-profiling methods to interrogate candidate BMEC pathways specifically triggered by brucipain, several pathways that potentially link brain inflammatory processes were identified, a finding congruent with the known role of PAR-2 as a mediator of inflammation. Overall, our data support a role for brucipain and BMEC PARs in trypanosome BBB transmigration, and as potential triggers for brain inflammation associated with the disease

    Structure, function, and evolution of plant NIMA-related kinases: implication for phosphorylation-dependent microtubule regulation

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    Negative Facial Expressions – But Not Visual Scenes – Enhance Human Working Memory in Younger and Older Participants

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    Many studies have investigated the influence of emotion on memory processes across the human lifespan. Some results have shown older adults (OA) performing better with positive stimuli, some with negative items, whereas some found no impact of emotional valence. Here we tested, in two independent studies, how younger adults (YA) and OA would perform in a visuospatial working memory (VSWM) task with positive, negative, and neutral images. The task consisted of identifying the new location of a stimulus in a crescent set of identical stimuli presented in different locations in a touch-screen monitor. In other words, participants should memorize the locations previously occupied to identify the new location. For each trial, the number of occupied locations increased until 8 or until a mistake was made. In study 1, 56 YA and 38 OA completed the task using images from the International Affective Picture System (IAPS). Results showed that, although YA outperformed OA, no effects of emotion were found. In study 2, 26 YA and 25 OA were tested using facial expressions as stimuli. Data from this study showed that negative faces facilitated performance and this effect did not differ between age groups. No differences were found between men and women. Taken together, our findings suggest that YA and OA’s VSWM can be influenced by the emotional valence of the information, though this effect was present only for facial stimuli. Presumably, this may have happened due to the social and biological importance of such stimuli, which are more effective in transmitting emotions than IAPS images. Critically, our results also indicate that the mixed findings in the literature about the influence of aging on the interactions between memory and emotion may be caused by the use of different stimuli and methods. This possibility should be kept in mind in future studies about memory and emotion across the lifespan
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