Increased risk of venous thrombosis by AB alleles of the ABO blood group and Factor V Leiden in a Brazilian population

Most cases of a predisposition to venous thrombosis are caused by resistance to activated protein C, associated in 95% of cases with the Factor V Leiden allele (FVL or R506Q). Several recent studies report a further increased risk of thrombosis by an association between the AB alleles of the ABO blood group and Factor V Leiden. The present study investigated this association with deep vein thrombosis (DVT) in individuals treated at the Hemocentro de Pernambuco in northeastern Brazil. A case-control comparison showed a significant risk of thrombosis in the presence of Factor V Leiden (OR = 10.1), which was approximately doubled when the AB alleles of the ABO blood group were present as well (OR = 22.3). These results confirm that the increased risk of deep vein thrombosis in the combined presence of AB alleles and Factor V Leiden is also applicable to the Brazilian population suggesting that ABO blood group typing should be routinely added to FVL in studies involving thrombosis

Expression Of Hypoxia-inducible Factor 1α In Mononuclear Phagocytes Infected With Leishmania Amazonensis

Increasing evidence indicates that hypoxia-inducible factor 1α (HIF-1α) can be upregulated in different cell types by nonhypoxic stimuli such as growth factors, cytokines, nitric oxide, lipopolysaccharides and a range of infectious microorganisms. In this study, the ability of the following mononuclear phagocytes to express HIF-1α is reported: mouse macrophages (mMΦ), human macrophages (hMΦ) and human dendritic cells (DC), parasitized in vitro with Leishmania amazonensis; as assessed by immunofluorescence microscopy. A logical explanation for HIF-1α expression might be that the mononuclear phagocytes became hypoxic after L. amazonensis infection. Using the hypoxia marker pimonidazole, observation revealed that L. amazonensis-infected cells were not hypoxic. In addition, experiments using a HIF-1α inhibitor, CdCl2, to treat L. amazonensis-infected macrophage cultures showed reduced parasite survival. These studies indicated that HIF-1α could play a role in adaptative and immune responses of mononuclear phagocytes presenting infection by the parasite L. amazonensis. © 2007 Elsevier B.V. All rights reserved.1142119125Wang, G.L., Semenza, G.L., Purification and characterization of hypoxia-inducible factor 1 (1995) J Biol Chem, 270, pp. 1230-1237Semenza, G.L., Regulation of physiological responses to continuous and intermittent hypoxia by hypoxia-inducible factor 1 (2006) Exp Physiol, 1, pp. 803-806Salceda, S., Caro, J., Hypoxia-inducible factor 1α (HIF-1α) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-induced changes (1997) J Biol Chem, 272, pp. 22642-22647Grimaldi Jr., G., Tesh, R.B., Leishmaniases of the New World: current concepts and implications for future research (1993) Clin Microbiol Rev, 6, pp. 230-250Arrais-Silva, W.W., Paffaro Jr., V.A., Yamada, A.T., Giorgio, S., Expression of hypoxia-inducible factor-1alpha in the cutaneous lesions of BALB/c mice infected with Leishmania amazonensis (2005) Exp Mol Pathol, 78, pp. 49-54Talks, K.L., Turley, H., Gatter, K.C., Maxwell, P.H., Pugh, C.W., Ratcliffe, P.J., The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages (2000) Am J Pathol, 157, pp. 411-421Burke, B., Tang, N., Corke, K.P., Tazzyman, D., Ameri, K., Wells, M., Expression of HIF-1alpha by human macrophages: implications for the use of macrophages in hypoxia-regulated cancer gene therapy (2002) J Pathol, 196, pp. 204-212Burke, B., Giannoudis, A., Corke, K.P., Gill, D., Wells, M., Ziegler-Heitbrock, L., Hypoxia-induced gene expression in human macrophages: implications for ischemic tissues and hypoxia-regulated gene therapy (2003) Am J Pathol, 163, pp. 1233-1243Lewis, C., Murdoch, C., Macrophage responses to hypoxia: implications for tumor progression and anti-cancer therapies (2005) Am J Pathol, 167, pp. 627-635Wang, G.L., Semenza, G.L., Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction (1993) Blood, 82, pp. 3610-3615Albina, J.E., Mastrofrancesco, B., Vessella, J.A., Louis, C.A., Henry Jr., W.L., Reichner, J.S., HIF-1 expression in healing wounds: HIF-1alpha induction in primary inflammatory cells by TNF-alpha (2001) Am J Physiol Cell Physiol, 281, pp. C1971-C1977Bilton, R.L., Booker, G.W., The subtle side to hypoxia inducible factor (HIFalpha) regulation (2003) Eur J Biochem, 270, pp. 791-798Dery, M.A., Michaud, M.D., Richard, D.E., Hypoxia-inducible factor 1: regulation by hypoxic and non-hypoxic activators (2005) Int J Biochem Cell Biol, 37, pp. 535-540Cramer, T., Yamanishi, Y., Clausen, B.E., Forster, I., Pawlinski, R., Mackman, N., HIF-1alpha is essential for myeloid cell-mediated inflammation (2003) Cell, 112, pp. 645-657Wakisaka, N., Kondo, S., Yoshizaki, T., Murono, S., Furukawa, M., Pagano, J.S., Epstein-Barr virus latent membrane protein 1 induces synthesis of hypoxia-inducible factor 1 alpha (2004) Mol Cell Biol, 24, pp. 5223-5234Kempf, V.A., Lebiedziejewski, M., Alitalo, K., Walzlein, J.H., Ehehalt, U., Fiebig, J., Activation of hypoxia-inducible factor-1 in bacillary angiomatosis. Evidence for a role of hypoxia-inducible factor-1 in bacterial infections (2005) Circulation, 111, pp. 1054-1062Peyssonnaux, C., Datta, V., Cramer, T., Doedens, A., Theodorakis, E.A., Gallo, R.L., HIF-1alpha expression regulates the bactericidal capacity of phagocytes (2005) J Clin Invest, 115, pp. 1806-1815Spear, W., Chan, D., Coppens, I., Johnson, R.S., Giaccia, A., Blader, I.J., The host cell transcription factor hypoxia-inducible factor 1 is required for Toxoplasma gondii growth and survival at physiological oxygen levels (2006) Cell Microbiol, 8, pp. 339-352Rupp, J., Gieffers, J., Klinger, M., van Zandbergen, G., Wrase, R., Maass, M., Chlamydia pneumoniae directly interferes with HIF-1alpha stabilization in human host cells (2007) Cell Microbiol, 9, pp. 2181-2191Barbieri, C.L., Giorgio, S., Merjan, A.J., Figueiredo, E.N., Glycosphingolipid antigens of Leishmania (Leishmania) amazonensis amastigotes identified by use of a monoclonal antibody (1993) Infect Immun, 61, pp. 2131-2137Degrossoli, A., Colhone, M.C., Arrais-Silva, W.W., Giorgio, S., Hypoxia modulates expression of the 70-kD heat shock protein and reduces Leishmania infection in macrophages (2004) J Biomed Sci, 11, pp. 847-854Bosque, F., Saravia, N.G., Valderrama, L., Milon, G., Distinct innate and acquired immune responses to Leishmania in putative susceptible and resistant human populations endemically exposed to L. (Viannia) panamensis infection (2000) Scand J Immunol, 51, pp. 533-541Nair, S.K., Boczkowski, D., Morse, M., Cumming, R.I., Lyerly, H.K., Gilboa, E., Induction of primary carcinoembryonic antigen (CEA)-specific cytotoxic T lymphocytes in vitro using human dendritic cells transfected with RNA (1998) Nat Biotechnol, 16, pp. 364-369Bosetto, M.C., Giorgio, S., Leishmania amazonensis: multiple receptor-ligand interactions are involved in amastigote infection of human dendritic cells (2007) Exp Parasitol, 116, pp. 306-310Degrossoli, A., Giorgio, S., Functional alterations in macrophages after hypoxia selection (2007) Exp Biol Med (Maywood), 232, pp. 88-95Colhone, M.C., Arrais-Silva, W.W., Picoli, C., Giorgio, S., Effect of hypoxia on macrophage infection by Leishmania amazonensis (2004) J Parasitol, 90, pp. 510-515Chun, Y.S., Choi, E., Kim, G.T., Choi, H., Kim, C.H., Lee, M.J., Cadmium blocks hypoxia-inducible factor (HIF)-1-mediated response to hypoxia by stimulating the proteasome-dependent degradation of HIF-1alpha (2000) Eur J Biochem, 267, pp. 4198-4204Mikami, M., Sadahira, Y., Haga, A., Otsuki, T., Wada, H., Sugihara, T., Hypoxia-inducible factor-1 drives the motility of the erythroid progenitor cell line, UT-7/Epo, via autocrine motility factor (2005) Exp Hematol, 33, pp. 531-541Chapman, J.D., Franko, A.J., Sharplin, J., A marker for hypoxic cells in tumours with potential clinical applicability (1981) Br J Cancer, 43, pp. 546-550Raleigh, J.A., Chou, S.C., Arteel, G.E., Horsman, M.R., Comparisons among pimonidazole binding, oxygen electrode measurements, and radiation response in C3H mouse tumors (1999) Radiat Res, 151, pp. 580-589Doege, K., Heine, S., Jensen, I., Jelkmann, W., Metzen, E., Inhibition of mitochondrial respiration elevates oxygen concentration but leaves regulation of hypoxia-inducible factor (HIF) intact (2005) Blood, 106, pp. 2311-2317Tanaka, H., Yamamoto, M., Hashimoto, N., Miyakoshi, M., Tamakawa, S., Yoshie, M., Hypoxia-independent overexpression of hypoxia-inducible factor 1alpha as an early change in mouse hepatocarcinogenesis (2006) Cancer Res, 66, pp. 11263-11270Sandau, K.B., Fandrey, J., Brune, B., Accumulation of HIF-1alpha under the influence of nitric oxide (2001) Blood, 97, pp. 1009-1015Chavez, J.C., LaManna, J.C., Activation of hypoxia-inducible factor-1 in the rat cerebral cortex after transient global ischemia: potential role of insulin-like growth factor-1 (2002) J Neurosci, 22, pp. 8922-8931Mateo, J., Garcia-Lecea, M., Cadenas, S., Hernandez, C., Moncada, S., Regulation of hypoxia-inducible factor-1alpha by nitric oxide through mitochondria-dependent and -independent pathways (2003) Biochem J, 376, pp. 537-544Blouin, C.C., Page, E.L., Soucy, G.M., Richard, D.E., Hypoxic gene activation by lipopolysaccharide in macrophages: implication of hypoxia-inducible factor 1alpha (2004) Blood, 103, pp. 1124-1130Zarember, K.A., Malech, H.L., HIF-1alpha: a master regulator of innate host defenses? (2005) J Clin Invest, 115, pp. 1702-1704Handman, E., Cell biology of Leishmania (1999) Adv Parasitol, 44, pp. 1-39Chang, K.P., Reed, S.G., McGwire, B.S., Soong, L., Leishmania model for microbial virulence: the relevance of parasite multiplication and pathoantigenicity (2003) Acta Trop, 85, pp. 375-390Chang, K.P., Human cutaneous lieshmania in a mouse macrophage line: propagation and isolation of intracellular parasites (1980) Science, 209, pp. 1240-1242Knowles, H.J., Mole, D.R., Ratcliffe, P.J., Harris, A.L., Normoxic stabilization of hypoxia-inducible factor-1alpha by modulation of the labile iron pool in differentiating U937 macrophages: effect of natural resistance-associated macrophage protein 1 (2006) Cancer Res, 66, pp. 2600-2607Oda, T., Hirota, K., Nishi, K., Takabuchi, S., Oda, S., Yamada, H., Activation of hypoxia-inducible factor 1 during macrophage differentiation (2006) Am J Physiol Cell Physiol, 291, pp. C104-C113Risbud, M.V., Guttapalli, A., Stokes, D.G., Hawkins, D., Danielson, K.G., Schaer, T.P., Nucleus pulposus cells express HIF-1alpha under normoxic culture conditions: a metabolic adaptation to the intervertebral disc microenvironment (2006) J Cell Biochem, 98, pp. 152-159Scharte, M., Jurk, K., Kehrel, B., Zarbock, A., Van Aken, H., Singbartl, K., IL-4 enhances hypoxia induced HIF-1alpha protein levels in human transformed intestinal cells (2006) FEBS Lett, 580, pp. 6399-6404Rasey, J.S., Hofstrand, P.D., Chin, L.K., Tewson, T.J., Characterization of [18F]fluoroetanidazole, a new radiopharmaceutical for detecting tumor hypoxia (1999) J Nucl Med, 40, pp. 1072-1079Bassnett, S., McNulty, R., The effect of elevated intraocular oxygen on organelle degradation in the embryonic chicken lens (2003) J Exp Biol, 206, pp. 4353-4361Sobhanifar, S., Aquino-Parsons, C., Stanbridge, E.J., Olive, P., Reduced expression of hypoxia-inducible factor-1alpha in perinecrotic regions of solid tumors (2005) Cancer Res, 65, pp. 7259-7266Jiang, B.H., Semenza, G.L., Bauer, C., Marti, H.H., Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension (1996) Am J Physiol, 271, pp. C1172-C1180Gazzinelli, R.T., Denkers, E.Y., Sher, A., Host resistance to Toxoplasma gondii: model for studying the selective induction of cell-mediated immunity by intracellular parasites (1993) Infect Agents Dis, 2, pp. 139-149Chandel, N.S., McClintock, D.S., Feliciano, C.E., Wood, T.M., Melendez, J.A., Rodriguez, A.M., Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing (2000) J Biol Chem, 275, pp. 25130-25138Fandrey, J., Genius, J., Reactive oxygen species as regulators of oxygen dependent gene expression (2000) Adv Exp Med Biol, 475, pp. 153-159Buchmüller-Rouiller, Y., Mauël, J., Impairment of the oxidative metabolism of mouse peritoneal macrophages by intracellular Leishmania spp. (1987) Infect Immun, 55, pp. 587-593Kima, P.E., The amastigote forms of Leishmania are experts at exploiting host cell processes to establish infection and persist (2007) Int J Parasitol, 37, pp. 1087-1096Descoteaux, A., Matlashewski, G., c-fos and tumor necrosis factor gene expression in Leishmania donovani-infected macrophages (1989) Mol Cell Biol, 9, pp. 5223-5227Buates, S., Matlashewski, G., Identification of genes induced by a macrophage activator, S-28463, using gene expression array analysis (2001) Antimicrob Agents Chemother, 45, pp. 1137-114

Movimentos de mudança na formação em saúde: da medicina comunitária às diretrizes curriculares Changing movements in health higher education: from community medicine to the activators course

Este ensaio busca refletir as diversas iniciativas pró-mudança na formação superior em saúde implantadas no Brasil. Esta análise histórica faz-se necessária tendo em vista a importância da sistematização e difusão das experiências anteriores para o auxilio na construção das novas propostas pró-mudança. Estamos hoje refletindo sobre processos ativos de ensino-aprendizagem por termos vivenciado propostas como a da Medicina Comunitária, o Projeto de Integração Docente Assistencial, o Programa UNI, o movimento da Rede UNIDA, a Lei de Diretrizes Curriculares, Educação Permanente em Saúde e o Curso de Ativadores. Avançamos a partir da construção da tentativa anterior. Não é necessária a descoberta da roda a todo momento. Ela pode ser adaptada e voltar a girar. O olhar para as experiências do passado e para as necessidades do presente ajuda na construção do futuro almejado.<br>This paper aims to ponder over the various pro-change initiatives in health higher education in Brazil. A historical analysis is needed since prior experiences systematization and diffusion are important on attempting to build new pro-change proposals. Today we are pondering over active processes of teaching-learning because we have experienced proposals such as Community Medicine, the Professor Integrative Assistence Project, the PROUNI Program, the Rede UNIDA movement, the Curricular Guideline Law, Permanent Education in Health and the Activators' course. There is no need to discover the wheel all the time. It can be adapted and start to spin again. Taking a look into the past experiences and into the present needs helps in building a desirable future