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Sample records for comp-ang1 recovers hematopoiesis

  1. COMP-Ang1 Recovers Hematopoiesis after Gamma-ray Irradiation in Mice

    International Nuclear Information System (INIS)

    Lee, Hae-June; Lee, Yoon-Jin; Kwon, Hee-Choong; Lee, Su-Jae; Bae, Sang-Woo; Lee, Yun-Sil; Kim, Sung-Ho

    2006-01-01

    It has been reported that angiopoietin (Ang1) enhanced the ability of hematopoietic stem cells (HSCs) to become quiescent and induced adhesion to bone, resulting in protection of the HSC compartment from myleosuppressive stress. Ang1 activates Tie2 receptors expressed on the vascular endothelial cells and HSCs expressing the receptor tyrosine kinase Tie2 are quiescent and antiapoptotic, comprise a sidepopulation of HSCs. COMP-Ang1 is generated protein, is a soluble, stable, and potent Ang1 variant by replacing the N-terminal portion of Ang1 with short coiled-coil domain of cartilage oligomeric matrix protein (COMP). Radio- and chemotherapy induces considerable damage of bone marrow. Herein, by using COMP-Ang1, we investigated the effect of COMP-Ang1 on restoration of hematopoiesis in bone marrow against radiation-induced myelosuppression

  2. COMP-angiopoietin-1 recovers molecular biomarkers of neuropathy and improves vascularisation in sciatic nerve of ob/ob mice.

    Directory of Open Access Journals (Sweden)

    Joanna Kosacka

    Full Text Available BACKGROUND: Leptin-deficient ob/ob mice are a model of type 2 diabetes induced peripheral neuropathy. Ob/ob mice exhibit obesity, insulin resistance, hyperglycaemia, and alterations of peripheral nerve fibres and endoneural microvessels. Here we test the hypothesis that cartilage oligomeric matrix protein (COMP-Ang-1, a soluble and stabile form of Ang-1 which promotes angiogenesis and nerve growth, improves regeneration of nerve fibres and endoneural microvessels in ob/ob mice. METHODS AND FINDINGS: COMP-Ang-1 (100 ng/ml or NaCl were intraperitoneally (i.p. injected into male (N = 184, 3-month old, ob/ob or ob/+ mice for 7 and 21 days. We measured expression of Nf68, GAP43, Cx32, Cx26, Cx43, and TNFα in sciatic nerves using Western blot analysis. To investigate the inflammation in sciatic nerves, numbers of macrophages and T-cells were counted after immunofluorescence staining. In ultrathin section, number of myelinated/non-mylinated nerve fibers, g-ratio, the thickness of Schwann cell basal lamina and microvessel endothelium were investigated. Endoneural microvessels were reconstructed with intracardial FITC injection. Treatment with COMP-Ang-1 over 21 days significantly reduced fasting blood glucose and plasma cholesterol concentrations compared to saline treated ob/ob mice. In addition, COMP-Ang-1 treatment: 1 up-regulated expression of Nf68 and GAP43; 2 improved expression of gap junction proteins including connexin 32 and 26; 3 suppressed the expression of TNFα and Cx43 and 4 led to decreased macrophage and T-cell infiltration in sciatic nerve of ob/ob mice. The significant changes of sciatic nerve ultrastructure were not observed after 21-day long COMP-Ang-1 treatment. COMP-Ang-1 treated ob/ob mice displayed regeneration of small-diameter endoneural microvessels. Effects of COMP-Ang-1 corresponded to increased phosphorylation of Akt and p38 MAPK upon Tie-2 receptor. CONCLUSIONS: COMP-Ang-1 recovers molecular biomarkers of neuropathy

  3. COMP-angiopoietin 1 increases proliferation, differentiation, and migration of stem-like cells through Tie-2-mediated activation of p38 MAPK and PI3K/Akt signal transduction pathways

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    Kook, Sung-Ho [Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Lim, Shin-Saeng [School of Dentistry and Dental Research Institute, Seoul National University, Seoul (Korea, Republic of); Cho, Eui-Sic; Lee, Young-Hoon; Han, Seong-Kyu; Lee, Kyung-Yeol [Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Kwon, Jungkee [College of Veterinary Medicine, Chonbuk National University, Jeonju (Korea, Republic of); Hwang, Jae-Won; Bae, Cheol-Hyeon [Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Seo, Young-Kwon [Research Institute of Biotechnology, Dongguk University, Seoul (Korea, Republic of); Lee, Jeong-Chae, E-mail: leejc88@jbnu.ac.kr [Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of)

    2014-12-12

    Highlights: • COMP-Ang1 induces Tie-2 activation in BMMSCs, but not in primary osteoblasts. • Tie-2 knockdown inhibits COMP-Ang1-stimulated proliferation and osteoblastogenesis. • Tie-2 knockdown prevents COMP-Ang1-induced activation of PI3K/Akt and p38 MAPK. • COMP-Ang1 induces migration of cells via activation of PI3K/Akt and CXCR4 pathways. • COMP-Ang1 stimulates in vivo migration of PDLSCs into a calvarial defect site of rats. - Abstract: Recombinant COMP-Ang1, a chimera of angiopoietin-1 (Ang1) and a short coiled-coil domain of cartilage oligomeric matrix protein (COMP), is under consideration as a therapeutic agent capable of inducing the homing of cells with increased angiogenesis. However, the potentials of COMP-Ang1 to stimulate migration of mesenchymal stem cells (MSCs) and the associated mechanisms are not completely understood. We examined the potential of COMP-Ang1 on bone marrow (BM)-MSCs, human periodontal ligament stem cells (PDLSCs), and calvarial osteoblasts. COMP-Ang1 augmented Tie-2 induction at protein and mRNA levels and increased proliferation and expression of runt-related transcription factor 2 (Runx2), osterix, and CXCR4 in BMMSCs, but not in osteoblasts. The COMP-Ang1-mediated increases were inhibited by Tie-2 knockdown and by treating inhibitors of phosphoinositide 3-kinase (PI3K), LY294002, or p38 mitogen-activated protein kinase (MAPK), SB203580. Phosphorylation of p38 MAPK and Akt was prevented by siRNA-mediated silencing of Tie-2. COMP-Ang1 also induced in vitro migration of BMMSCs and PDLSCs. The induced migration was suppressed by Tie-2 knockdown and by CXCR4-specific peptide antagonist or LY294002, but not by SB203580. Furthermore, COMP-Ang1 stimulated the migration of PDLSCs into calvarial defect site of rats. Collectively, our results demonstrate that COMP-Ang1-stimulated proliferation, differentiation, and migration of progenitor cells may involve the Tie-2-mediated activation of p38 MAPK and PI3K/Akt pathways.

  4. COMP-angiopoietin 1 increases proliferation, differentiation, and migration of stem-like cells through Tie-2-mediated activation of p38 MAPK and PI3K/Akt signal transduction pathways

    International Nuclear Information System (INIS)

    Kook, Sung-Ho; Lim, Shin-Saeng; Cho, Eui-Sic; Lee, Young-Hoon; Han, Seong-Kyu; Lee, Kyung-Yeol; Kwon, Jungkee; Hwang, Jae-Won; Bae, Cheol-Hyeon; Seo, Young-Kwon; Lee, Jeong-Chae

    2014-01-01

    Highlights: • COMP-Ang1 induces Tie-2 activation in BMMSCs, but not in primary osteoblasts. • Tie-2 knockdown inhibits COMP-Ang1-stimulated proliferation and osteoblastogenesis. • Tie-2 knockdown prevents COMP-Ang1-induced activation of PI3K/Akt and p38 MAPK. • COMP-Ang1 induces migration of cells via activation of PI3K/Akt and CXCR4 pathways. • COMP-Ang1 stimulates in vivo migration of PDLSCs into a calvarial defect site of rats. - Abstract: Recombinant COMP-Ang1, a chimera of angiopoietin-1 (Ang1) and a short coiled-coil domain of cartilage oligomeric matrix protein (COMP), is under consideration as a therapeutic agent capable of inducing the homing of cells with increased angiogenesis. However, the potentials of COMP-Ang1 to stimulate migration of mesenchymal stem cells (MSCs) and the associated mechanisms are not completely understood. We examined the potential of COMP-Ang1 on bone marrow (BM)-MSCs, human periodontal ligament stem cells (PDLSCs), and calvarial osteoblasts. COMP-Ang1 augmented Tie-2 induction at protein and mRNA levels and increased proliferation and expression of runt-related transcription factor 2 (Runx2), osterix, and CXCR4 in BMMSCs, but not in osteoblasts. The COMP-Ang1-mediated increases were inhibited by Tie-2 knockdown and by treating inhibitors of phosphoinositide 3-kinase (PI3K), LY294002, or p38 mitogen-activated protein kinase (MAPK), SB203580. Phosphorylation of p38 MAPK and Akt was prevented by siRNA-mediated silencing of Tie-2. COMP-Ang1 also induced in vitro migration of BMMSCs and PDLSCs. The induced migration was suppressed by Tie-2 knockdown and by CXCR4-specific peptide antagonist or LY294002, but not by SB203580. Furthermore, COMP-Ang1 stimulated the migration of PDLSCs into calvarial defect site of rats. Collectively, our results demonstrate that COMP-Ang1-stimulated proliferation, differentiation, and migration of progenitor cells may involve the Tie-2-mediated activation of p38 MAPK and PI3K/Akt pathways

  5. Vascular Endothelial Growth Factor and Angiopoietin-1 Stimulate Postnatal Hematopoiesis by Recruitment of Vasculogenic and Hematopoietic Stem Cells

    Science.gov (United States)

    Hattori, Koichi; Dias, Sergio; Heissig, Beate; Hackett, Neil R.; Lyden, David; Tateno, Masatoshi; Hicklin, Daniel J.; Zhu, Zhenping; Witte, Larry; Crystal, Ronald G.; Moore, Malcolm A.S.; Rafii, Shahin

    2001-01-01

    Tyrosine kinase receptors for angiogenic factors vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) are expressed not only by endothelial cells but also by subsets of hematopoietic stem cells (HSCs). To further define their role in the regulation of postnatal hematopoiesis and vasculogenesis, VEGF and Ang-1 plasma levels were elevated by injecting recombinant protein or adenoviral vectors expressing soluble VEGF165, matrix-bound VEGF189, or Ang-1 into mice. VEGF165, but not VEGF189, induced a rapid mobilization of HSCs and VEGF receptor (VEGFR)2+ circulating endothelial precursor cells (CEPs). In contrast, Ang-1 induced delayed mobilization of CEPs and HSCs. Combined sustained elevation of Ang-1 and VEGF165 was associated with an induction of hematopoiesis and increased marrow cellularity followed by proliferation of capillaries and expansion of sinusoidal space. Concomitant to this vascular remodeling, there was a transient depletion of hematopoietic activity in the marrow, which was compensated by an increase in mobilization and recruitment of HSCs and CEPs to the spleen resulting in splenomegaly. Neutralizing monoclonal antibody to VEGFR2 completely inhibited VEGF165, but not Ang-1–induced mobilization and splenomegaly. These data suggest that temporal and regional activation of VEGF/VEGFR2 and Ang-1/Tie-2 signaling pathways are critical for mobilization and recruitment of HSCs and CEPs and may play a role in the physiology of postnatal angiogenesis and hematopoiesis. PMID:11342585

  6. Enhanced expression of Ang-(1-7 during pregnancy

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    Brosnihan K.B.

    2004-01-01

    Full Text Available Pregnancy is a physiological condition characterized by a progressive increase of the different components of the renin-angiotensin system (RAS. The physiological consequences of the stimulated RAS in normal pregnancy are incompletely understood, and even less understood is the question of how this system may be altered and contribute to the hypertensive disorders of pregnancy. Findings from our group have provided novel insights into how the RAS may contribute to the physiological condition of pregnancy by showing that pregnancy increases the expression of both the vasodilator heptapeptide of the RAS, angiotensin-(1-7 [Ang-(1-7], and of a newly cloned angiotensin converting enzyme (ACE homolog, ACE2, that shows high catalytic efficiency for Ang II metabolism to Ang-(1-7. The discovery of ACE2 adds a new dimension to the complexity of the RAS by providing a new arm that may counter-regulate the activity of the vasoconstrictor component, while amplifying the vasodilator component. The studies reviewed in this article demonstrate that Ang-(1-7 increases in plasma and urine of normal pregnant women. In preeclamptic subjects we showed that plasma Ang-(1-7 was suppressed as compared to the levels found in normal pregnancy. In addition, kidney and urinary levels of Ang-(1-7 were increased in pregnant rats coinciding with the enhanced detection and expression of ACE2. These findings support the concept that in normal pregnancy enhanced ACE2 may counteract the elevation in tissue and circulating Ang II by increasing the rate of conversion to Ang-(1-7. These findings provide a basis for the physiological role of Ang-(1-7 and ACE2 during pregnancy.

  7. Intracavernous Delivery of a Designed Angiopoietin-1 Variant Rescues Erectile Function by Enhancing Endothelial Regeneration in the Streptozotocin-Induced Diabetic Mouse

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    Jin, Hai-Rong; Kim, Woo Jean; Song, Jae Sook; Piao, Shuguang; Choi, Min Ji; Tumurbaatar, Munkhbayar; Shin, Sun Hwa; Yin, Guo Nan; Koh, Gou Young; Ryu, Ji-Kan; Suh, Jun-Kyu

    2011-01-01

    OBJECTIVE Patients with diabetic erectile dysfunction often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors. We examined the effectiveness of the potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, in promoting cavernous endothelial regeneration and restoring erectile function in diabetic animals. RESEARCH DESIGN AND METHODS Four groups of mice were used: controls; streptozotocin (STZ)-induced diabetic mice; STZ-induced diabetic mice treated with repeated intracavernous injections of PBS; and STZ-induced diabetic mice treated with COMP-Ang1 protein (days −3 and 0). Two and 4 weeks after treatment, we measured erectile function by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations, Western blot analysis, and cGMP quantification. We also performed a vascular permeability test. RESULTS Local delivery of the COMP-Ang1 protein significantly increased cavernous endothelial proliferation, endothelial nitric oxide (NO) synthase (NOS) phosphorylation, and cGMP expression compared with that in the untreated or PBS-treated STZ-induced diabetic group. The changes in the group that received COMP-Ang1 restored erectile function up to 4 weeks after treatment. Endothelial protective effects, such as marked decreases in the expression of p47phox and inducible NOS, in the generation of superoxide anion and nitrotyrosine, and in the number of apoptotic cells in the corpus cavernosum tissue, were noted in COMP-Ang1–treated STZ-induced diabetic mice. An intracavernous injection of COMP-Ang1 completely restored endothelial cell-cell junction proteins and decreased cavernous endothelial permeability. COMP-Ang1–induced promotion of cavernous angiogenesis and erectile function was abolished by the NOS inhibitor, N-nitro-L-arginine methyl ester, but not by the NADPH oxidase inhibitor, apocynin. CONCLUSIONS These findings support the concept of cavernous

  8. Ang-(1-7) exerts protective role in blood-brain barrier damage by the balance of TIMP-1/MMP-9.

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    Wu, Jitao; Zhao, Duo; Wu, Shuang; Wang, Dan

    2015-02-05

    Cerebrovascular disease (CVD) ranks as the top three health risks, specially cerebral ischemia characterized with the damage of blood-brain barrier (BBB). The angiotensin Ang-(1-7) was proven to have a protective effect on cerebrovascular diseases. However, its role on blood-brain barrier and the underlying molecular mechanism remains unclear. In this study, Ang-(1-7) significantly relieved damage of ischemia reperfusion injury on blood-brain barrier in cerebral ischemia reperfusion injury (IRI) rats. Furthermore, its treatment attenuated BBB permeability and brain edema. Similarly, Ang-(1-7) also decreased the barrier permeability of brain endothelial cell line RBE4. Further analysis showed that Ang-(1-7) could effectively restore tight junction protein (claudin-5 and zonula occludens ZO-1) expression levels both in IRI-rats and hypoxia-induced RBE4 cells. Furthermore, Ang-(1-7) stimulation down-regulated hypoxia-induced matrix metalloproteinase-9 (MMP-9) levels, whose silencing with (matrix metalloproteinase-9 hemopexin domain) MMP9-PEX inhibitor significantly increased the expression of claudin-5 and ZO-1. Further mechanism analysis demonstrated that Ang-(1-7) might junction protein levels by tissue inhibitor of metalloproteinase 1 (TIMP1)-MMP9 pathway, because Ang-(1-7) enhanced TIMP1 expression, whose silencing obviously attenuated the inhibitor effect of Ang-(1-7) on MMP-9 levels and decreased Ang-(1-7)-triggered increase in claudin-5 and ZO-1. Together, this study demonstrated a protective role of Ang-(1-7) in IRI-induced blood-brain barrier damage by TIMP1-MMP9-regulated tight junction protein expression. Accordingly, Ang-(1-7) may become a promising therapeutic agent against IRI and its complications. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Gut microbiota sustains hematopoiesis

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, Kim

    2017-01-01

    In this issue of Blood, Josefsdottir et al provide substantial evidence that commensal gut microbes regulate and sustain normal steady-state hematopoiesis.1......In this issue of Blood, Josefsdottir et al provide substantial evidence that commensal gut microbes regulate and sustain normal steady-state hematopoiesis.1...

  10. New Insights into the Pro-Inflammatory Activities of Ang1 on Neutrophils: Induction of MIP-1β Synthesis and Release.

    Directory of Open Access Journals (Sweden)

    Elizabeth Dumas

    Full Text Available We reported the expression of angiopoietin Tie2 receptor on human neutrophils and the capacity of angiopoietins (Ang1 and Ang2 to induce pro-inflammatory activities, such as platelet-activating factor synthesis, β2-integrin activation and neutrophil migration. Recently, we observed differential effects between both angiopoietins, namely, the capacity of Ang1, but not Ang2, to promote rapid interleukin-8 synthesis and release, as well as neutrophil viability. Herein, we addressed whether Ang1 and/or Ang2 could modulate the synthesis and release of macrophage inflammatory protein-1β (MIP-1β by neutrophils. Neutrophils were isolated from blood of healthy volunteers; intracellular and extracellular MIP-1β protein concentrations were assessed by ELISA. After 24 hours, the basal intracellular and extracellular MIP-1β protein concentrations were ≈500 and 100 pg/106 neutrophils, respectively. Treatment with Ang1 (10 nM increased neutrophil intracellular and extracellular MIP-1β concentrations by 310 and 388% respectively. Pretreatment with PI3K (LY294002, p38 MAPK (SB203580 and MEK (U0126 inhibitors completely inhibited Ang1-mediated increase of MIP-1β intracellular and extracellular protein levels. Pretreatment with NF-κB complex inhibitors, namely Bay11-7085 and IKK inhibitor VII or with a transcription inhibitor (actinomycin D and protein synthesis inhibitor (cycloheximide, did also abrogate Ang1-mediated increase of MIP-1β intracellular and extracellular protein levels. We validated by RT-qPCR analyses the effect of Ang1 on the induction of MIP-1β mRNA levels. Our study is the first one to report Ang1 capacity to induce MIP-1β gene expression, protein synthesis and release from neutrophils, and that these effects are mediated by PI3K, p38 MAPK and MEK activation and downstream NF-κB activation.

  11. Ang Rita 1

    OpenAIRE

    Loomis, Molly

    2012-01-01

    .wav and .mp3 versions of audio file Ang Rita describes in Sherpa difference aspects of his life as a yak herder and yak herding culture. Tape includes native names for yak, birth and death ceremonies; castration practices; differences between Sherpa and Tibetan customs regarding yaks; herding yaks as a child; herding calls; interactions with wolves; grazing practices; concerns about decline of yak herding and the environmental consequences; the future of yak herding; famous yak herders; t...

  12. COMP-1 promotes competitive advantage of nematode sperm.

    Science.gov (United States)

    Hansen, Jody M; Chavez, Daniela R; Stanfield, Gillian M

    2015-03-19

    Competition among sperm to fertilize oocytes is a ubiquitous feature of sexual reproduction as well as a profoundly important aspect of sexual selection. However, little is known about the cellular mechanisms sperm use to gain competitive advantage or how these mechanisms are regulated genetically. In this study, we utilize a forward genetic screen in Caenorhabditis elegans to identify a gene, comp-1, whose function is specifically required in competitive contexts. We show that comp-1 functions in sperm to modulate their migration through and localization within the reproductive tract, thereby promoting their access to oocytes. Contrary to previously described models, comp-1 mutant sperm show no defects in size or velocity, thereby defining a novel pathway for preferential usage. Our results indicate not only that sperm functional traits can influence the outcome of sperm competition, but also that these traits can be modulated in a context-dependent manner depending on the presence of competing sperm.

  13. COMP-1 promotes competitive advantage of nematode sperm

    Science.gov (United States)

    Hansen, Jody M; Chavez, Daniela R; Stanfield, Gillian M

    2015-01-01

    Competition among sperm to fertilize oocytes is a ubiquitous feature of sexual reproduction as well as a profoundly important aspect of sexual selection. However, little is known about the cellular mechanisms sperm use to gain competitive advantage or how these mechanisms are regulated genetically. In this study, we utilize a forward genetic screen in Caenorhabditis elegans to identify a gene, comp-1, whose function is specifically required in competitive contexts. We show that comp-1 functions in sperm to modulate their migration through and localization within the reproductive tract, thereby promoting their access to oocytes. Contrary to previously described models, comp-1 mutant sperm show no defects in size or velocity, thereby defining a novel pathway for preferential usage. Our results indicate not only that sperm functional traits can influence the outcome of sperm competition, but also that these traits can be modulated in a context-dependent manner depending on the presence of competing sperm. DOI: http://dx.doi.org/10.7554/eLife.05423.001 PMID:25789512

  14. Silencing MR-1 attenuates inflammatory damage in mice heart induced by AngII

    International Nuclear Information System (INIS)

    Dai, Wenjian; Chen, Haiyang; Jiang, Jiandong; Kong, Weijia; Wang, Yiguang

    2010-01-01

    Myofibrillogenesis regulator-1(MR-1) can aggravate cardiac hypertrophy induced by angiotensin(Ang) II in mice through activation of NF-κB signaling pathway, and nuclear transcription factor (NF)-κB and activator protein-1(AP-1) regulate inflammatory and immune responses by increasing the expression of specific inflammatory genes in various tissues including heart. Whether inhibition of MR-1 expression will attenuate AngII-induced inflammatory injury in mice heart has not been explored. Herein, we monitored the activation of NF-κB and AP-1, together with expression of pro-inflammatory of interleukin(IL)-6, tumor necrosis factor(TNF)-α, vascular-cell adhesion molecule (VCAM)-1, platelet endothelial cell adhesion molecule (PECAM), and inflammatory cell infiltration in heart of mice which are induced firstly by AngII (PBS),then received MR-1-siRNA or control-siRNA injecting. We found that the activation of NF-κB and AP-1 was inhibited significantly, together with the decreased expression of IL-6, TNF-α, VCAM-1, and PECAM in AngII-induced mice myocardium in MR-1-siRNA injection groups compared with control-siRNA injecting groups. However, the expression level of MR-1 was not an apparent change in PBS-infused groups than in unoperation groups, and MR-1-siRNA do not affect the expression of MR-1 in PBS-infused mice. Our findings suggest that silencing MR-1 protected mice myocardium against inflammatory injury induced by AngII by suppression of pro-inflammatory transcription factors NF-κB and AP-1 signaling pathway.

  15. IGF-1 prevents ANG II-induced skeletal muscle atrophy via Akt- and Foxo-dependent inhibition of the ubiquitin ligase atrogin-1 expression

    Science.gov (United States)

    Yoshida, Tadashi; Semprun-Prieto, Laura; Sukhanov, Sergiy

    2010-01-01

    Congestive heart failure is associated with activation of the renin-angiotensin system and skeletal muscle wasting. Angiotensin II (ANG II) has been shown to increase muscle proteolysis and decrease circulating and skeletal muscle IGF-1. We have shown previously that skeletal muscle-specific overexpression of IGF-1 prevents proteolysis and apoptosis induced by ANG II. These findings indicated that downregulation of IGF-1 signaling in skeletal muscle played an important role in the wasting effect of ANG II. However, the signaling pathways and mechanisms whereby IGF-1 prevents ANG II-induced skeletal muscle atrophy are unknown. Here we show ANG II-induced transcriptional regulation of two ubiquitin ligases atrogin-1 and muscle ring finger-1 (MuRF-1) that precedes the reduction of skeletal muscle IGF-1 expression, suggesting that activation of atrogin-1 and MuRF-1 is an initial mechanism leading to skeletal muscle atrophy in response to ANG II. IGF-1 overexpression in skeletal muscle prevented ANG II-induced skeletal muscle wasting and the expression of atrogin-1, but not MuRF-1. Dominant-negative Akt and constitutively active Foxo-1 blocked the ability of IGF-1 to prevent ANG II-mediated upregulation of atrogin-1 and skeletal muscle wasting. Our findings demonstrate that the ability of IGF-1 to prevent ANG II-induced skeletal muscle wasting is mediated via an Akt- and Foxo-1-dependent signaling pathway that results in inhibition of atrogin-1 but not MuRF-1 expression. These data suggest strongly that atrogin-1 plays a critical role in mechanisms of ANG II-induced wasting in vivo. PMID:20228261

  16. Isthmin 1 (ism1) is required for normal hematopoiesis in developing zebrafish.

    Science.gov (United States)

    Berrun, Arturo; Harris, Elena; Stachura, David L

    2018-01-01

    Hematopoiesis is an essential and highly regulated biological process that begins with hematopoietic stem cells (HSCs). In healthy organisms, HSCs are responsible for generating a multitude of mature blood cells every day, yet the molecular pathways that instruct HSCs to self-renew and differentiate into post-mitotic blood cells are not fully known. To understand these molecular pathways, we investigated novel genes expressed in hematopoietic-supportive cell lines from the zebrafish (Danio rerio), a model system increasingly utilized to uncover molecular pathways important in the development of other vertebrate species. We performed RNA sequencing of the transcriptome of three stromal cell lines derived from different stages of embryonic and adult zebrafish and identified hundreds of highly expressed transcripts. For our studies, we focused on isthmin 1 (ism1) due to its shared synteny with its human gene ortholog and because it is a secreted protein. To characterize ism1, we performed loss-of-function experiments to identify if mature blood cell production was disrupted. Myeloid and erythroid lineages were visualized and scored with transgenic zebrafish expressing lineage-specific markers. ism1 knockdown led to reduced numbers of neutrophils, macrophages, and erythrocytes. Analysis of clonal methylcellulose assays from ism1 morphants also showed a reduction in total hematopoietic stem and progenitor cells (HSPCs). Overall, we demonstrate that ism1 is required for normal generation of HSPCs and their downstream progeny during zebrafish hematopoiesis. Further investigation into ism1 and its importance in hematopoiesis may elucidate evolutionarily conserved processes in blood formation that can be further investigated for potential clinical utility.

  17. Isthmin 1 (ism1) is required for normal hematopoiesis in developing zebrafish

    Science.gov (United States)

    Berrun, Arturo; Harris, Elena

    2018-01-01

    Hematopoiesis is an essential and highly regulated biological process that begins with hematopoietic stem cells (HSCs). In healthy organisms, HSCs are responsible for generating a multitude of mature blood cells every day, yet the molecular pathways that instruct HSCs to self-renew and differentiate into post-mitotic blood cells are not fully known. To understand these molecular pathways, we investigated novel genes expressed in hematopoietic-supportive cell lines from the zebrafish (Danio rerio), a model system increasingly utilized to uncover molecular pathways important in the development of other vertebrate species. We performed RNA sequencing of the transcriptome of three stromal cell lines derived from different stages of embryonic and adult zebrafish and identified hundreds of highly expressed transcripts. For our studies, we focused on isthmin 1 (ism1) due to its shared synteny with its human gene ortholog and because it is a secreted protein. To characterize ism1, we performed loss-of-function experiments to identify if mature blood cell production was disrupted. Myeloid and erythroid lineages were visualized and scored with transgenic zebrafish expressing lineage-specific markers. ism1 knockdown led to reduced numbers of neutrophils, macrophages, and erythrocytes. Analysis of clonal methylcellulose assays from ism1 morphants also showed a reduction in total hematopoietic stem and progenitor cells (HSPCs). Overall, we demonstrate that ism1 is required for normal generation of HSPCs and their downstream progeny during zebrafish hematopoiesis. Further investigation into ism1 and its importance in hematopoiesis may elucidate evolutionarily conserved processes in blood formation that can be further investigated for potential clinical utility. PMID:29758043

  18. AVE0991, a nonpeptide analogue of Ang-(1-7), attenuates aging-related neuroinflammation.

    Science.gov (United States)

    Jiang, Teng; Xue, Liu-Jun; Yang, Yang; Wang, Qing-Guang; Xue, Xiao; Ou, Zhou; Gao, Qing; Shi, Jian-Quan; Wu, Liang; Zhang, Ying-Dong

    2018-04-17

    During the aging process, chronic neuroinflammation induced by microglia is detrimental for the brain and contributes to the etiology of several aging-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. As a newly identified axis of renin-angiotensin system, ACE2/Ang-(1-7)/MAS1 axis plays a crucial role in modulating inflammatory responses under various pathological conditions. However, its relationship with aging-related neuroinflammation is less studied so far. In this study, by using SAMP8 mice, an animal model of accelerated aging, we revealed that the neuroinflammation in the aged brain might be attributed to a decreased level of Ang-(1-7). More importantly, we provided evidence that AVE0991, a nonpeptide analogue of Ang-(1-7), attenuated the aging-related neuroinflammation via suppression of microglial-mediated inflammatory response through a MAS1 receptor-dependent manner. Meanwhile, this protective effect might be ascribed to the M2 activation of microglia induced by AVE0991. Taken together, these findings reveal the association of Ang-(1-7) with the inflammatory response in the aged brain and uncover the potential of its nonpeptide analogue AVE0991 in attenuation of aging-related neuroinflammation.

  19. Oral delivery of ACE2/Ang-(1-7) bioencapsulated in plant cells protects against experimental uveitis and autoimmune uveoretinitis.

    Science.gov (United States)

    Shil, Pollob K; Kwon, Kwang-Chul; Zhu, Ping; Verma, Amrisha; Daniell, Henry; Li, Qiuhong

    2014-12-01

    Hyperactivity of the renin-angiotensin system (RAS) resulting in elevated Angiotensin II (Ang II) contributes to all stages of inflammatory responses including ocular inflammation. The discovery of angiotensin-converting enzyme 2 (ACE2) has established a protective axis of RAS involving ACE2/Ang-(1-7)/Mas that counteracts the proinflammatory and hypertrophic effects of the deleterious ACE/AngII/AT1R axis. Here we investigated the hypothesis that enhancing the systemic and local activity of the protective axis of the RAS by oral delivery of ACE2 and Ang-(1-7) bioencapsulated in plant cells would confer protection against ocular inflammation. Both ACE2 and Ang-(1-7), fused with the non-toxic cholera toxin subunit B (CTB) were expressed in plant chloroplasts. Increased levels of ACE2 and Ang-(1-7) were observed in circulation and retina after oral administration of CTB-ACE2 and Ang-(1-7) expressing plant cells. Oral feeding of mice with bioencapsulated ACE2/Ang-(1-7) significantly reduced endotoxin-induced uveitis (EIU) in mice. Treatment with bioencapsulated ACE2/Ang-(1-7) also dramatically decreased cellular infiltration, retinal vasculitis, damage and folding in experimental autoimmune uveoretinitis (EAU). Thus, enhancing the protective axis of RAS by oral delivery of ACE2/Ang-(1-7) bioencapsulated in plant cells provide an innovative, highly efficient and cost-effective therapeutic strategy for ocular inflammatory diseases.

  20. Reduced Ang2 expression in aging endothelial cells.

    Science.gov (United States)

    Hohensinner, P J; Ebenbauer, B; Kaun, C; Maurer, G; Huber, K; Wojta, J

    2016-06-03

    Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic rats.

    Science.gov (United States)

    Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

    2017-08-01

    The local role of the renin angiotensin system (RAS) was documented recently beside its conventional systemic functions. Studies showed that the effector angiotensin II (AngII) alters bone health, while inhibition of the angiotensin converting enzyme (ACE-1) preserved these effects. The newly identified Ang1-7 exerts numerous beneficial effects opposing the AngII. Thus, the current study examines the role of Ang1-7 in mediating the osteo-preservative effects of ACEI (captopril) through the G-protein coupled Mas receptor using an ovariectomized (OVX) rat model of osteoporosis. 8 weeks after the surgical procedures, captopril was administered orally (40mgkg -1 d -1 ), while the specific Mas receptor blocker (A-779) was delivered at infusion rate of 400ngkg -1 min -1 for 6 weeks. Bone metabolic markers were measured in serum and urine. Minerals concentrations were quantified in serum, urine and femoral bones by inductive coupled plasma mass spectroscopy (ICP-MS). Trabecular and cortical morphometry was analyzed in the right distal femurs using micro-CT. Finally, the expressions of RAS peptides, enzymes and receptors along with the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) were determined femurs heads. OVX animals markedly showed altered bone metabolism and mineralization along with disturbed bone micro-structure. Captopril significantly restored the metabolic bone bio-markers and corrected Ca 2+ and P values in urine and bones of estrogen deficient rats. Moreover, the trabecular and cortical morphometric features were repaired by captopril in OVX groups. Captopril also improved the expressions of ACE-2, Ang1-7, Mas and OPG, while abolished OVX-induced up-regulation of ACE-1, AngII, Ang type 1 receptor (AT1R) and RANKL. Inhibition of Ang1-7 cascade by A-779 significantly eradicated captopril protective effects on bone metabolism, mineralization and micro-structure. A-779 also restored OVX effects on RANKL expression and ACE-1/AngII/AT1R

  2. GM-CSF ameliorates microvascular barrier integrity via pericyte-derived Ang-1 in wound healing.

    Science.gov (United States)

    Yan, Min; Hu, Yange; Yao, Min; Bao, Shisan; Fang, Yong

    2017-11-01

    Skin wound healing involves complex coordinated interactions of cells, tissues, and mediators. Maintaining microvascular barrier integrity is one of the key events for endothelial homeostasis during wound healing. Vasodilation is observed after vasoconstriction, which causes blood vessels to become porous, facilitates leukocyte infiltration and aids angiogenesis at the wound-area, postinjury. Eventually, vessel integrity has to be reestablished for vascular maturation. Numerous studies have found that granulocyte macrophage colony-stimulating factor (GM-CSF) accelerates wound healing by inducing recruitment of repair cells into the injury area and releases of cytokines. However, whether GM-CSF is involving in the maintaining of microvascular barrier integrity and the underlying mechanism remain still unclear. Aim of this study was to investigate the effects of GM-CSF on modulation of microvascular permeability in wound healing and underlying mechanisms. Wound closure and microvascular leakage was investigated using a full-thickness skin wound mouse model after GM-CSF intervention. The endothelial permeability was measured by Evans blue assay in vivo and in vitro endothelium/pericyte co-culture system using a FITC-Dextran permeability assay. To identify the source of angiopoietin-1 (Ang-1), double staining is used in vivo and ELISA and qPCR are used in vitro. To determine the specific effect of Ang-1 on GM-CSF maintaining microvascular stabilization, Ang-1 siRNA was applied to inhibit Ang-1 production in vivo and in vitro. Wound closure was significantly accelerated and microvascular leakage was ameliorated after GM-CSF treatment in mouse wound sites. GM-CSF decreased endothelial permeability through tightening endothelial junctions and increased Ang-1 protein level that was derived by perictye. Furthermore, applications of siRNAAng-1 inhibited GM-CSF mediated protection of microvascular barrier integrity both in vivo and in vitro. Our data indicate that GM

  3. Reduced Ang2 expression in aging endothelial cells

    International Nuclear Information System (INIS)

    Hohensinner, P.J.; Ebenbauer, B.; Kaun, C.; Maurer, G.; Huber, K.; Wojta, J.

    2016-01-01

    Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. -- Highlights: •Endothelial cells display signs of aging before reaching proliferative senescence. •Aging endothelial cells express more angiopoietin 1 and less angiopoietin 2 than young endothelial cells. •Migratory capacity is reduced in aging endothelial cells.

  4. Reduced Ang2 expression in aging endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Hohensinner, P.J., E-mail: philipp.hohensinner@meduniwien.ac.at [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ebenbauer, B. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); Kaun, C.; Maurer, G. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Huber, K. [Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); 3rd Medical Department, Wilhelminenhospital, Vienna (Austria); Sigmund Freud University, Medical Faculty, Vienna (Austria); Wojta, J. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); Core Facilities, Medical University of Vienna, Vienna (Austria)

    2016-06-03

    Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. -- Highlights: •Endothelial cells display signs of aging before reaching proliferative senescence. •Aging endothelial cells express more angiopoietin 1 and less angiopoietin 2 than young endothelial cells. •Migratory capacity is reduced in aging endothelial cells.

  5. Endothelial Jagged-1 Is Necessary for Homeostatic and Regenerative Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Michael G. Poulos

    2013-09-01

    Full Text Available The bone marrow (BM microenvironment is composed of multiple niche cells that, by producing paracrine factors, maintain and regenerate the hematopoietic stem cell (HSC pool (Morrison and Spradling, 2008. We have previously demonstrated that endothelial cells support the proper regeneration of the hematopoietic system following myeloablation (Butler et al., 2010; Hooper et al., 2009; Kobayashi et al., 2010. Here, we demonstrate that expression of the angiocrine factor Jagged-1, supplied by the BM vascular niche, regulates homeostatic and regenerative hematopoiesis through a Notch-dependent mechanism. Conditional deletion of Jagged-1 in endothelial cells (Jag1(ECKO mice results in a profound decrease in hematopoiesis and premature exhaustion of the adult HSC pool, whereas quantification and functional assays demonstrate that loss of Jagged-1 does not perturb vascular or mesenchymal compartments. Taken together, these data demonstrate that the instructive function of endothelial-specific Jagged-1 is required to support the self-renewal and regenerative capacity of HSCs in the adult BM vascular niche.

  6. The ACE-2/Ang1-7/Mas cascade enhances bone structure and metabolism following angiotensin-II type 1 receptor blockade.

    Science.gov (United States)

    Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

    2017-07-15

    The renin angiotensin system (RAS) regulates numerous systemic functions and is expressed locally in skeletal tissues. Angiotensin1-7 (Ang1-7) is a beneficial member of the RAS, and the therapeutic effects of a large number of angiotensin receptors blockers (ARBs) are mediated by an Ang1-7-dependent cascade. This study examines whether the reported osteo-preservative effects of losartan are mediated through the angiotensin converting enzyme2 (ACE-2)/Ang1-7/Mas pathway in ovariectomized (OVX) rats. Sham and OVX animals received losartan (10mg/kg/d p.o.) for 6 weeks. A specific Mas receptor blocker (A-779) was delivered via mini-osmotic pumps during the losartan treatment period. Serum and urine bone metabolism biomarker levels were measured. Bone trabecular and cortical morphometry were quantified in distal femurs, whereas mineral contents were estimated in ashed bones, serum and urine. Finally, the expression of RAS components, the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) was determined. Losartan significantly improved the elevated bone metabolism marker levels and altered trabecular and cortical structures in OVX animals, and restored normal urinary and skeletal mineral levels. Mas receptor inhibition significantly abolished all osteo-protective effects of losartan and enhanced the deleterious effects of OVX. Losartan enhanced OVX-induced up-regulation of ACE-1, AngII, angiotensin type 1 (AT 1 ) receptor and RANKL expression, and increased ACE-2, Ang1-7, Mas and OPG expression in OVX animals. However, A-779 significantly eradicated the effects of losartan on RAS components and RANKL/OPG expression. Thus, Ang1-7 are involved in the osteo-preservative effects of losartan via Mas receptor, which may add therapeutic value to this well-known antihypertensive agent. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. The Effect of the Thioether-Bridged, Stabilized Angiotensin-(1–7 Analogue Cyclic Ang-(1–7 on Cardiac Remodeling and Endothelial Function in Rats with Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Matej Durik

    2012-01-01

    Full Text Available Modulation of renin-angiotensin system (RAS by angiotensin-(1–7 (Ang-(1–7 is an attractive approach to combat the detrimental consequences of myocardial infarction (MI. However Ang-(1–7 has limited clinical potential due to its unfavorable pharmacokinetic profile. We investigated effects of a stabilized, thioether-bridged analogue of Ang-(1–7 called cyclic Ang-(1–7 in rat model of myocardial infarction. Rats underwent coronary ligation or sham surgery. Two weeks thereafter infusion with 0.24 or 2.4 μg/kg/h cAng-(1–7 or saline was started for 8 weeks. Thereafter, cardiac morphometric and hemodynamic variables as wells as aortic endothelial function were measured. The average infarct size was 13.8% and was not changed by cAng-(1–7 treatment. MI increased heart weight and myocyte size, which was restored by cAng-(1–7 to sham levels. In addition, cAng-(1–7 lowered left ventricular end-diastolic pressure and improved endothelial function. The results suggest that cAng-(1–7 is a promising new agent in treatment of myocardial infarction and warrant further research.

  8. Focal splenic masses of the extramedullary hematopoiesis

    International Nuclear Information System (INIS)

    Incedayi, M.; Sivrioglu, A.

    2012-01-01

    Full text: Extramedullary hematopoiesis arises from pleuripotential stem cells distributed throughout the body. It is most common in patients with congenital hemolytic anemia, such as thalassemia, sickle cell anemia and hereditary spherocytosis as a response to ineffective red blood cell formation. Although microscopic foci of Extramedullary hematopoiesis are commonly seen in the spleen and liver parenchyma, focal mass-like lesion of extramedullary hematopoiesis in the liver and spleen are rare. We report a case of intrasplenic focal extramedullary hematopoiesis lesions and the imaging features of extramedullary hematopoiesis on computed tomography and magnetic resonance imaging. Extramedullary hematopoiesis should always be considered as a diagnosis in a patient with a known hematological disorder

  9. Effects of LHRH and ANG II on prolactin stimulation are mediated by hypophysial AT1 receptor subtype.

    Science.gov (United States)

    Becú-Villalobos, D; Lacau-Mengido, I M; Thyssen, S M; Díaz-Torga, G S; Libertun, C

    1994-02-01

    We have used the nonpeptide angiotensin II (ANG II) receptor antagonists losartan (receptor subtype AT1) and PD-123319 (AT2) to determine the participation of ANG II receptor subtypes in luteinizing hormone-releasing hormone (LHRH)-induced prolactin release in a perifusion study using intact pituitaries in vitro. LHRH (1.85 x 10(-7) M) released prolactin consistently, whereas losartan (10(-5) M) abolished prolactin response without modifying basal prolactin or luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release. PD-123319 (10(-5) M) had no effect on basal or LHRH-induced prolactin, LH, or FSH release. We also determined that the effect of ANG II on prolactin release was mediated by the same receptor subtype. In adenohypophysial cells dispersed in vitro ANG II (10(-8) M) released prolactin. Losartan (10(-7) and 10(-6) M), but not PD-123319, inhibited this effect. We conclude that in intact hypophyses of 15-day-old female rats the effect of LHRH on prolactin release is readily demonstrated. LHRH-induced prolactin release appears to be mediated by ANG II acting in a paracrine manner on AT1 receptors located on lactotrophs.

  10. Mass-like extramedullary hematopoiesis: imaging features

    Energy Technology Data Exchange (ETDEWEB)

    Ginzel, Andrew W. [Synergy Radiology Associates, Houston, TX (United States); Kransdorf, Mark J.; Peterson, Jeffrey J.; Garner, Hillary W. [Mayo Clinic, Department of Radiology, Jacksonville, FL (United States); Murphey, Mark D. [American Institute for Radiologic Pathology, Silver Spring, MD (United States)

    2012-08-15

    To report the imaging appearances of mass-like extramedullary hematopoiesis (EMH), to identify those features that are sufficiently characteristic to allow a confident diagnosis, and to recognize the clinical conditions associated with EMH and the relative incidence of mass-like disease. We retrospectively identified 44 patients with EMH; 12 of which (27%) had focal mass-like lesions and formed the study group. The study group consisted of 6 male and 6 female subjects with a mean age of 58 years (range 13-80 years). All 12 patients underwent CT imaging and 3 of the 12 patients had undergone additional MR imaging. The imaging characteristics of the extramedullary hematopoiesis lesions in the study group were analyzed and recorded. The patient's clinical presentation, including any condition associated with extramedullary hematopoiesis, was also recorded. Ten of the 12 (83%) patients had one or more masses located along the axial skeleton. Of the 10 patients with axial masses, 9 (90%) had multiple masses and 7 (70%) demonstrated internal fat. Eight patients (80%) had paraspinal masses and 4 patients (40%) had presacral masses. Seven patients (70%) had splenomegaly. Eleven of the 12 patients had a clinical history available for review. A predisposing condition for extramedullary hematopoiesis was present in 10 patients and included various anemias (5 cases; 45%), myelofibrosis/myelodysplastic syndrome (4 cases; 36%), and marrow proliferative disorder (1 case; 9%). One patient had no known predisposing condition. Mass-like extramedullary hematopoiesis most commonly presents as multiple, fat-containing lesions localized to the axial skeleton. When these imaging features are identified, extramedullary hematopoiesis should be strongly considered, particularly when occurring in the setting of a predisposing medical condition. (orig.)

  11. Novel mechanism of cardiac protection by valsartan: synergetic roles of TGF-β1 and HIF-1α in Ang II-mediated fibrosis after myocardial infarction.

    Science.gov (United States)

    Sui, Xizhong; Wei, Hongchao; Wang, Dacheng

    2015-08-01

    Transforming growth factor (TGF)-β1 is a known factor in angiotensin II (Ang II)-mediated cardiac fibrosis after myocardial infarction (MI). Hypoxia inducible factor-1 (Hif-1α) was recently demonstrated to involve in the tissue fibrosis and influenced by Ang II. However, whether Hif-1α contributed to the Ang II-mediated cardiac fibrosis after MI, and whether interaction or synergetic roles between Hif-1α and TGF-β pathways existed in the process was unclear. In vitro, cardiac cells were incubated under hypoxia or Ang II to mimic ischaemia. In vivo, valsartan was intravenously injected into Sprague-Dawley rats with MI daily for 1 week; saline and hydralazine (another anti-hypertensive agent like valsartan) was used as control. The fibrosis-related proteins were detected by Western blotting. Cardiac structure and function were assessed with multimodality methods. We demonstrated in vitro that hypoxia would induce the up-regulation of Ang II, TGF-β/Smad and Hif-1α, which further induced collagen accumulation. By blocking with valsartan, a blocker of Ang II type I (AT1) receptor, we confirmed that the up-regulation of TGF-β/Smad and Hif-1α was through the Ang II-mediated pathway. By administering TGF-β or dimethyloxalylglycine, we determined that both TGF-β/Smad and Hif-1α contributed to Ang II-mediated collagen accumulation and a synergetic effect between them was observed. Consistent with in vitro results, valsartan significantly attenuated the expression of TGF-β/Smad, Hif-1α and fibrosis-related protein in rats after MI. Heart function, infarcted size, wall thickness as well as myocardial vascularization of ischaemic hearts were also significantly improved by valsartan compared with saline and hydralazine. Our study may provide novel insights into the mechanisms of Ang II-induced cardiac fibrosis as well as into the cardiac protection of valsartan. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and

  12. MRI features of epidural extramedullary hematopoiesis

    Energy Technology Data Exchange (ETDEWEB)

    Alorainy, Ibrahim A. E-mail: alorainy@ksu.edu.sa; Al-Asmi, Abdullah R.; Carpio, Raquel del

    2000-07-01

    A case of {beta}-thalassemia intermedia with spinal cord compression due to extramedullary hematopoiesis, which was successfully treated by blood transfusion, is presented. Emphasis was made on the MRI appearance of extramedullary hematopoiesis on different pulse sequences. The theories that aimed to explain the involvement of the epidural space by extramedullary hematopoiesis are discussed.

  13. MRI features of epidural extramedullary hematopoiesis

    International Nuclear Information System (INIS)

    Alorainy, Ibrahim A.; Al-Asmi, Abdullah R.; Carpio, Raquel del

    2000-01-01

    A case of β-thalassemia intermedia with spinal cord compression due to extramedullary hematopoiesis, which was successfully treated by blood transfusion, is presented. Emphasis was made on the MRI appearance of extramedullary hematopoiesis on different pulse sequences. The theories that aimed to explain the involvement of the epidural space by extramedullary hematopoiesis are discussed

  14. Standardization of radioimmunoassay for dosage of angiotensin II (ang-II) and its methodological evaluation; Padronizacao do radioimunoensaio para dosagem de angiotensina II (ang-II) e sua validacao metodologica

    Energy Technology Data Exchange (ETDEWEB)

    Mantovani, Milene; Mecawi, Andre S.; Elias, Lucila L.K.; Antunes-Rodrigues, Jose, E-mail: llelias@fmrp.usp.b, E-mail: antunes@fmrp.usp.b [Universidade de Sao Paulo (FMRP/USP), Ribeirao Preto, SP (Brazil). Faculdade de Medicina

    2011-10-26

    This paper standardizes the radioimmunoassay (RIA) for dosage of ANG-II of rats, after experimental conditions of saline hypertonic (2%), treating with losartan (antagonist of ANG-II), hydric privation, and acute hemorrhage (25%). After that, the plasmatic ANG-II was extracted for dosage of RIA, whose sensitiveness was of 1.95 pg/m L, with detection of 1.95 to 1000 pg/m L. The treatment with saline reduced the concentration of ANG-II, while the administration pf losartan, the hydric administration and the hemorrhage increase the values, related to the control group. Those results indicate variations in the plasmatic concentration of ANG-II according to the experimental protocols, validating the method for evaluation of activity renin-angiotensin

  15. Perturbed hematopoiesis in the Tc1 mouse model of Down syndrome

    OpenAIRE

    Alford, Kate A.; Slender, Amy; Vanes, Lesley; Li, Zhe; Fisher, Elizabeth M. C.; Nizetic, Dean; Orkin, Stuart H.; Roberts, Irene; Tybulewicz, Victor L. J.

    2010-01-01

    Trisomy of human chromosome 21 (Hsa21) results in Down syndrome (DS), a disorder that affects many aspects of physiology, including hematopoiesis. DS children have greatly increased rates of acute lymphoblastic leukemia and acute megakaryoblastic leukemia (AMKL); DS newborns present with transient myeloproliferative disorder (TMD), a preleukemic form of AMKL. TMD and DS-AMKL almost always carry an acquired mutation in GATA1 resulting in exclusive synthesis of a truncated protein (GATA1s), sug...

  16. Application of determination of PRA, Ang II and IGF-1 levels in the study of typing of essential hypertension

    International Nuclear Information System (INIS)

    Lu Yongyi; Chen Qun; Yang Yongqing

    2010-01-01

    Objective: To study the clinical application of determination of plasma renin activity (PRA), Angiotensin II (Ang II ) and insulin-like growth factor-1 (IGF-1) levels in typing of essential hypertension (EH). Methods: Determined the levels of PRA and Aug II in 256 patients with EH and 70 healthy volunteers (as control group) by radioimmunoassay, and measured IGF-1 level by enzyme immunoassay. Research on the typing of EH and the difference between the groups. Results: The PRA and Ang II in control group was (0.432±0.236) μg·L -1 ·h -1 and (31.7±7.4) μg/L respectively. In 256 patients with EH, PRA was increased, normal and decreased in 18.0%, 71.8% and 10.2% respectively, while the level of Ang II was increased, normal and decreased in 12.9%, 76.2% and 10.9% respectively. The IGF-1 levels in 256 patients with EH were increased following the increase of blood pressure. Conclusion: Typing of EH patients with PRA and Ang II as well as the determination of IGF-1 were useful in treating and following up the patients with EH. (authors)

  17. Renal extramedullary hematopoiesis: interstitial and glomerular pathology.

    Science.gov (United States)

    Alexander, Mariam P; Nasr, Samih H; Kurtin, Paul J; Casey, Edward T; Hernandez, Loren P Herrera; Fidler, Mary E; Sethi, Sanjeev; Cornell, Lynn D

    2015-12-01

    Renal extramedullary hematopoiesis is rarely recognized in the antemortem setting. We identified 14 patients with renal extramedullary hematopoiesis on antemortem specimens from 1994 to 2015. The mean age was 68 years (range 47-87 years); males predominated (M:F=9:5). All presented with renal insufficiency, including five (36%) with acute kidney injury. The mean serum creatinine at biopsy was 2.9 mg/dl (range 1.2-7.3 mg/dl). All had proteinuria (mean 7.9 g/24 h; range 0.5-28; n=13), including 9 with ≥3 g/24 h. Renal extramedullary hematopoiesis appeared histologically as an interstitial infiltrate (n=12) and/or a perirenal infiltrate (n=3) or mass-like lesion (n=1). Five were misdiagnosed as interstitial nephritis. Concurrent glomerular disease was prevalent and included fibrillary-like glomerulonephritis (n=3), chronic thrombotic microangiopathy (n=5), focal segmental glomerulosclerosis (n=6), and diabetic glomerulosclerosis (n=2). All patients had an underlying hematologic malignancy: primary myelofibrosis in 9, myeloproliferative neoplasm not otherwise specified in 1, essential thrombocythemia in 1, polycythemia vera in 1, and plasma cell myeloma in 2. Clinical follow-up was available in 12 patients, mean of 29 months (range 4-120 months). In 10 patients for whom treatment history could be obtained, 9 were treated with chemotherapy, and 1 was treated with steroids. The mean creatinine at last follow-up was 2 mg/dl (range 1.2-3.9 mg/dl) (n=9). Ten patients died in the follow-up period from their underlying hematological disease and had persistent renal disease. The two remaining patients had persistent chronic kidney disease. Renal extramedullary hematopoiesis should be considered in the differential diagnosis of interstitial infiltrates, particularly in the presence of a glomerulopathy and a hematologic malignancy.

  18. Expression of Ang-2 and VEGF in the endometriosis

    Directory of Open Access Journals (Sweden)

    Xiao-Li Chen

    2016-01-01

    Full Text Available Objective: To detect the expression of Ang-2 and VEGF in the endometriosis (EMT, and to explore the correlation of Ang-2 and VEGF with the pathogenesis of EMT. Methods: A total of 60 patients with EMT who were confirmed by laparoscopy and admitted in our hospital from August, 2014 to August, 2015 were included in the study and served as the observation group; moreover, 60 women who came for laparoscopy at the same stage were served as the control group. A volume of 5mL morning fasting elbow venous blood in the two groups was extracted, standing in the room temperature for 1h, centrifuged at 3 500 r/min for 20 min. The supernatant was extracted and stored at -70 ℃ for inspection. During the laparoscopy, a volume of 5 mL peritoneal fluid was collected, standing in the room temperature for 1 h, centrifuged at 3 500 r/min for 20 min. The supernatant was extracted and stored at -70 ℃ for inspection. ELISA was used to detect the levels of Ang-2 and VEGF. Results: The levels of Ang-2 and VEGF in the serum and peritoneal fluid in the observation group were significantly higher than those in the control group (P<0.05. The serum Ang-2 level in the severe patients was significantly higher than that in the mild patients, while the comparison of VEGF was not statistically significant. The levels of Ang-2 and VEGF in the peritoneal fluid in the severe patients were significantly higher than those in the mild patients. Conclusions: Ang-2 and VEGF can promote the angiogenesis in EMT patients, and their high expressions in the serum and peritoneal fluid are correlated with the occurrence and development of EMT; therefore, detection of the levels of Ang-2 and VEGF is of great significance in estimating the progression of EMT in the clinic.

  19. Role of Mas Receptor Antagonist A799 in Renal Blood Flow Response to Ang 1-7 after Bradykinin Administration in Ovariectomized Estradiol-Treated Rats

    Directory of Open Access Journals (Sweden)

    Aghdas Dehghani

    2015-01-01

    Full Text Available Background. The accompanied role of Mas receptor (MasR, bradykinin (BK, and female sex hormone on renal blood flow (RBF response to angiotensin 1-7 is not well defined. We investigated the role of MasR antagonist (A779 and BK on RBF response to Ang 1-7 infusion in ovariectomized estradiol-treated rats. Methods. Ovariectomized Wistar rats received estradiol (OVE or vehicle (OV for two weeks. Catheterized animals were subjected to BK and A799 infusion and mean arterial pressure (MAP, RBF, and renal vascular resistance (RVR responses to Ang 1-7 (0, 100, and 300 ng kg−1 min−1 were determined. Results. Percentage change of RBF (%RBF in response to Ang1-7 infusion increased in a dose-dependent manner. In the presence of BK, when MasR was not blocked, %RBF response to Ang 1-7 in OVE group was greater than OV group significantly (P<0.05. Infusion of 300 ng kg−1 min−1 Ang 1-7 increased RBF by 6.9±1.9% in OVE group versus 0.9±1.8% in OV group. However when MasR was blocked, %RBF response to Ang 1-7 in OV group was greater than OVE group insignificantly. Conclusion. Coadministration of BK and A779 compared to BK alone increased RBF response to Ang 1-7 in vehicle treated rats. Such observation was not seen in estradiol treated rats.

  20. Zebrafish hoxd4a acts upstream of meis1.1 to direct vasculogenesis, angiogenesis and hematopoiesis.

    Directory of Open Access Journals (Sweden)

    Aseervatham Anusha Amali

    Full Text Available Mice lacking the 4th-group paralog Hoxd4 display malformations of the anterior vertebral column, but are viable and fertile. Here, we report that zebrafish embryos having decreased function of the orthologous hoxd4a gene manifest striking perturbations in vasculogenesis, angiogenesis and primitive and definitive hematopoiesis. These defects are preceded by reduced expression of the hemangioblast markers scl1, lmo2 and fli1 within the posterior lateral plate mesoderm (PLM at 13 hours post fertilization (hpf. Epistasis analysis revealed that hoxd4a acts upstream of meis1.1 but downstream of cdx4 as early as the shield stage in ventral-most mesoderm fated to give rise to hemangioblasts, leading us to propose that loss of hoxd4a function disrupts hemangioblast specification. These findings place hoxd4a high in a genetic hierarchy directing hemangioblast formation downstream of cdx1/cdx4 and upstream of meis1.1. An additional consequence of impaired hoxd4a and meis1.1 expression is the deregulation of multiple Hox genes implicated in vasculogenesis and hematopoiesis which may further contribute to the defects described here. Our results add to evidence implicating key roles for Hox genes in their initial phase of expression early in gastrulation.

  1. Activation pattern of ACE2/Ang-(1-7) and ACE/Ang II pathway in course of heart failure assessed by multiparametric MRI in vivo in Tgαq*44 mice.

    Science.gov (United States)

    Tyrankiewicz, Urszula; Olkowicz, Mariola; Skórka, Tomasz; Jablonska, Magdalena; Orzylowska, Anna; Bar, Anna; Gonet, Michal; Berkowicz, Piotr; Jasinski, Krzysztof; Zoladz, Jerzy A; Smolenski, Ryszard T; Chlopicki, Stefan

    2018-01-01

    Here, we analyzed systemic (plasma) and local (heart/aorta) changes in ACE/ACE-2 balance in Tgαq*44 mice in course of heart failure (HF). Tgαq*44 mice with cardiomyocyte-specific Gαq overexpression and late onset of HF were analyzed at different age for angiotensin pattern in plasma, heart, and aorta using liquid chromatography/mass spectrometry, for progression of HF by in vivo magnetic resonance imaging under isoflurane anesthesia, and for physical activity by voluntary wheel running. Six-month-old Tgαq*44 mice displayed decreased ventricle radial strains and impaired left atrial function. At 8-10 mo, Tgαq*44 mice showed impaired systolic performance and reduced voluntary wheel running but exhibited preserved inotropic reserve. At 12 mo, Tgαq*44 mice demonstrated a severe impairment of basal cardiac performance and modestly compromised inotropic reserve with reduced voluntary wheel running. Angiotensin analysis in plasma revealed an increase in concentration of angiotensin-(1-7) in 6- to 10-mo-old Tgαq*44 mice. However, in 12- to 14-mo-old Tgαq*44 mice, increased angiotensin II was noted with a concomitant increase in Ang III, Ang IV, angiotensin A, and angiotensin-(1-10). The pattern of changes in the heart and aorta was also compatible with activation of ACE2, followed by activation of the ACE pathway. In conclusion, mice with cardiomyocyte Gαq protein overexpression develop HF that is associated with activation of the systemic and the local ACE/Ang II pathway. However, it is counterbalanced by a prominent ACE2/Ang-(1-7) activation, possibly allowing to delay decompensation. NEW & NOTEWORTHY Changes in ACE/ACE-2 balance were analyzed based on measurements of a panel of nine angiotensins in plasma, heart, and aorta of Tgαq*44 mice in relation to progression of heart failure (HF) characterized by multiparametric MRI and exercise performance. The early stage of HF was associated with upregulation of the ACE2/angiotensin-(1-7) pathway, whereas the end

  2. Extramedullary hematopoiesis: A report of two cases.

    Science.gov (United States)

    Zhang, Huan-Zhu; Li, Ying; Liu, Xin; Chen, Bao-Rong; Yao, Guo-Hua; Peng, Yu-Na

    2016-12-01

    Extramedullary hematopoiesis (EMH) is defined as hematopoiesis occurring in organs outside of the bone marrow. The present report describes two cases of thalassemic patients with paraspinal medullary hematopoiesis and analyzes the clinical manifestations, imaging, pathology, diagnosis and treatment of EMH. In addition, a supplementary review of previously published cases is provided along with a review of the related literature. Computed tomography (CT) of the first case revealed multiple paraspinal masses, and the largest was 6.2×8.0 cm in diameter. Likewise, CT of the second patient revealed multiple paraspinal masses in the bottom of the left thoracic cavity, and the largest was measured 10.1×10.5 cm. The two cases underwent surgical biopsy and the findings were compatible with a diagnosis of EMH. In conclusion, EMH is a compatible and rare disease, and should be distinguished from other neoplasms. EMH must considered when masses with characteristic radiologic appearance are detected in patients with thalassemia intermedia.

  3. Ginger Stimulates Hematopoiesis via Bmp Pathway in Zebrafish

    Science.gov (United States)

    Ferri-Lagneau, Karine F.; Moshal, Karni S.; Grimes, Matthew; Zahora, Braden; Lv, Lishuang; Sang, Shengmin; Leung, TinChung

    2012-01-01

    Background Anemia is a hematologic disorder with decreased number of erythrocytes. Erythropoiesis, the process by which red blood cells differentiate, are conserved in humans, mice and zebrafish. The only known agents available to treat pathological anemia are erythropoietin and its biologic derivatives. However, erythropoietin therapy elicits unwanted side-effects, high cost and intravenous or subcutaneous injection, warranting the development of a more cost effective and non-peptide alternative. Ginger (Zingiber officinale) has been widely used in traditional medicine; however, to date there is no scientific research documenting the potential of ginger to stimulate hematopoiesis. Methodology/Principal Findings Here, we utilized gata1:dsRed transgenic zebrafish embryos to investigate the effect of ginger extract on hematopoiesis in vivo and we identified its bioactive component, 10-gingerol. We confirmed that ginger and 10-gingerol promote the expression of gata1 in erythroid cells and increase the expression of hematopoietic progenitor markers cmyb and scl. We also demonstrated that ginger and 10-gingerol can promote the hematopoietic recovery from acute hemolytic anemia in zebrafish, by quantifying the number of circulating erythroid cells in the dorsal aorta using video microscopy. We found that ginger and 10-gingerol treatment during gastrulation results in an increase of bmp2b and bmp7a expression, and their downstream effectors, gata2 and eve1. At later stages ginger and 10-gingerol can induce bmp2b/7a, cmyb, scl and lmo2 expression in the caudal hematopoietic tissue area. We further confirmed that Bmp/Smad pathway mediates this hematopoiesis promoting effect of ginger by using the Bmp-activated Bmp type I receptor kinase inhibitors dorsomorphin, LND193189 and DMH1. Conclusions/Significance Our study provides a strong foundation to further evaluate the molecular mechanism of ginger and its bioactive components during hematopoiesis and to investigate their

  4. VEGF and IHH rescue definitive hematopoiesis in Gata-4 and Gata-6-deficient murine embryoid bodies.

    Science.gov (United States)

    Pierre, Monique; Yoshimoto, Momoko; Huang, Lan; Richardson, Matthew; Yoder, Mervin C

    2009-09-01

    Murine embryonic stem cells can be differentiated into embryoid bodies (EBs), which serve as an in vitro model recapitulating many aspects of embryonic yolk sac hematopoiesis. Differentiation of embryonic stem cells deficient in either Gata-4 or Gata-6 results in EBs with disrupted visceral endoderm (VE). While lack of VE has detrimental effects on hematopoiesis in vivo, it is unclear whether lack of VE affects hematopoiesis in EBs. Therefore, we compared Gata-4 null (G4N) and Gata-6 null (G6N) EBs with wild-type EBs to assess their ability to commit to hematopoietic cells. EB VE formation was examined using cell-sorting techniques and analysis visceral endoderm gene expression. Hematopoietic progenitor potential of EBs cultured under various conditions was assessed using colony-forming assays. Definitive erythroid, granulocyte-macrophage, and mixed colonies were significantly reduced in G4N and G6N EBs compared to wild-type EBs. Vascular endothelial growth factor (VEGF) expression and secretion were also reduced in both G4N and G6N EBs, consistent with VE serving as a site of VEGF production. Addition of exogenous VEGF(165), to EB cultures completely rescued definitive colony-forming cells in G4N and G6N EBs. This rescue response could be blocked by addition of soluble Flk-1 Fc to EB cultures. Similarly, addition of exogenous Indian hedgehog to EB cultures also recovers the diminishment in definitive hematopoiesis in a reversible manner. These results suggest that the absence of VE in G4N and G6N EBs does not prevent emergence of definitive progenitors from EBs. However, the decreased level of VEGF and Indian hedgehog production in VE devoid G4N and G6N EBs attenuates definitive hematopoietic progenitor cell expansion.

  5. Standardization of radioimmunoassay for dosage of angiotensin II (ang-II) and its methodological evaluation

    International Nuclear Information System (INIS)

    Mantovani, Milene; Mecawi, Andre S.; Elias, Lucila L.K.; Antunes-Rodrigues, Jose

    2011-01-01

    This paper standardizes the radioimmunoassay (RIA) for dosage of ANG-II of rats, after experimental conditions of saline hypertonic (2%), treating with losartan (antagonist of ANG-II), hydric privation, and acute hemorrhage (25%). After that, the plasmatic ANG-II was extracted for dosage of RIA, whose sensitiveness was of 1.95 pg/m L, with detection of 1.95 to 1000 pg/m L. The treatment with saline reduced the concentration of ANG-II, while the administration pf losartan, the hydric administration and the hemorrhage increase the values, related to the control group. Those results indicate variations in the plasmatic concentration of ANG-II according to the experimental protocols, validating the method for evaluation of activity renin-angiotensin

  6. Surgical treatment of an unusual case of pelvic extramedullary hematopoiesis.

    Science.gov (United States)

    Khen-Dunlop, Naziha; Girot, Robert; Brunelle, Francis; Révillon, Yann; Nihoul-Fékété, Claire; Sarnacki, Sabine

    2006-07-01

    Extramedullary hematopoiesis affects about 15% of the patients treated for thalassemia intermedia. Usually seen in adulthood, the most common location is the paraspinal region. Diagnosis and treatment of extramedullary hematopoiesis located in the pelvis of a young 15-year-old girl is discussed. The young age of the patient and the uncommon site of the mass first lead to the diagnosis of an ovarian dermoid cyst. Because of the clinical history and the typical feature on computed tomography scan, extramedullary hematopoiesis was concluded. A specific treatment based on blood transfusion and hydroxyurea was first proposed but remained inefficient. Surgical excision was thus successfully performed. Whereas surgery is limited to spinal cord compression in paraspinal extramedullary hematopoiesis, this observation argues for surgical treatment in symptomatic intraabdominal extramedullary hematopoiesis when medical treatment fails.

  7. Functional evidence for alternative ANG II-forming pathways in hamster cardiovascular system

    NARCIS (Netherlands)

    Nishimura, H; Buikema, H; Baltatu, O; Ganten, D; Urata, H

    1998-01-01

    Like human chymase, hamster chymase is an ANG II-forming enzyme, but pathophysiological roles of chymase are still unknown. We determined the functional conversion of ANG I and [Pro(11), D-Ala(12)]ANG I, a chymase-selective substrate, to ANG II in the hamster cardiovascular system. ANG I and

  8. Four stages of hepatic hematopoiesis in human embryos and fetuses.

    Science.gov (United States)

    Fanni, D; Angotzi, F; Lai, F; Gerosa, C; Senes, G; Fanos, V; Faa, G

    2018-03-01

    The liver is a major hematopoietic organ during embryonic and fetal development in humans. Its hematopoietic activity starts during the first weeks of gestation and continues until birth. During this period the liver is colonized by undifferentiated hematopoietic stem cells (HSCs) that gradually differentiate and once mature, enter the circulatory system through the hepatic sinusoids, this process is called hepatic hematopoiesis. The morphology of hepatic hematopoiesis, has been studied in humans through the years, and led to a characterization of all the cell types that make up these phenomena. Studies on murine models also helped to describe the extent of hepatic hematopoiesis at different gestational ages. Using this knowledge, we attempted to describe how hepatic hematopoiesis morphologically evolves as gestation progresses, in human embryos and fetuses. Thus, we observed a total of 32 tissue specimens obtained from the livers of embryos and fetuses at different gestational ages. Basing our observations on the four stages of liver hematopoiesis identified by Sasaki and Sonoda in mice, we also described four consecutive stages of liver hematopoiesis in humans, which resulted to be highly similar to those described in murine models.

  9. Extramedullary Hematopoiesis: An Unusual Finding in Subdural Hematomas

    Directory of Open Access Journals (Sweden)

    Rong Li

    2011-01-01

    Full Text Available We present a case of a 59-year-old man who was found to have clusters of hyperchromatic, small, round nucleated cells within a subdural hematoma removed after a skull fracture. Immunohistochemistry study confirmed that the cells were hematopoietic components predominantly composed of normoblasts. In this paper, we describe the clinical and pathological findings. A brief review of published information on extramedullary hematopoiesis in subdural hematoma and the mechanisms of pathogenesis are also discussed. While extramedullary hematopoiesis is seen anecdotally by neuropathologists in chronic subdural hematomas, only a few cases are documented in the literature. Furthermore, extramedullary hematopoiesis in subdural hematoma can pose a diagnostic challenge for general pathologists who encounter subdural hematoma evacuations seldom in their surgical pathology practices.

  10. Chronic Treatment with Ang-(1-7 Reverses Abnormal Reactivity in the Corpus Cavernosum and Normalizes Diabetes-Induced Changes in the Protein Levels of ACE, ACE2, ROCK1, ROCK2 and Omega-Hydroxylase in a Rat Model of Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Mariam H. M. Yousif

    2014-01-01

    Full Text Available Angiotensin-(1-7 [Ang-(1-7] may have beneficial effects in diabetes mellitus-induced erectile dysfunction (DMIED but its molecular actions in the diabetic corpus cavernosum (CC are not known. We characterized the effects of diabetes and/or chronic in vivo administration of Ang-(1-7 on vascular reactivity in the rat corpus cavernosum (CC and on protein expression levels of potential downstream effectors of the renin-angiotensin-aldosterone system (RAAS such as angiotensin-converting enzyme (ACE, ACE2, Rho kinases 1 and 2 (ROCK1 and ROCK2, and omega-hydroxylase, the cytochrome-P450 enzyme that metabolizes arachidonic acid to form the vasoconstrictor, 20-hydroxyeicosatetraenoic acid. Streptozotocin-treated rats were chronicically administered Ang-(1-7 with or without A779, a Mas receptor antagonist, during weeks 4 to 6 of diabetes. Ang-(1-7 reversed diabetes-induced abnormal reactivity to vasoactive agents (endothelin-1, phenylepherine, and carbachol in the CC without correcting hyperglycemia. Six weeks of diabetes led to elevated ACE, ROCK1, ROCK 2, and omega-hydroxylase and a concomitant decrease in ACE2 protein expression levels that were normalized by Ang-(1-7 treatment but not upon coadministration of A779. These data are supportive of the notion that the beneficial effects of Ang-(1-7 in DMIED involve counterregulation of diabetes-induced changes in ACE, ACE2, Rho kinases, and omega-hydroxylase proteins in the diabetic CC via a Mas receptor-dependent mechanism.

  11. Kierkegaard, a Escola da Angústia e a Psicoterapia

    Directory of Open Access Journals (Sweden)

    Ana Maria Lopez Calvo de Feijoo

    Full Text Available Este artigo busca refletir sobre a relação estabelecida por Soren Kierkegaard, na voz do pseudônimo Vigilius Haufniensis, entre angústia e Psicologia. A Psicologia surge, nesse contexto, como a ciência cuja atmosfera é angústia. Primeiramente, são apresentadas as considerações de Haufniensis sobre a angústia como determinação existencial. Em seguida, exemplificam-se as formas particulares de expressão da angústia por meio de um conto de Grimm, intitulado João sem medo. Observa-se que é da tensão entre o universal e o particular que nasce, por um salto qualitativo, a possibilidade de uma existência singular. Ao considerar o tema angústia como centro de investigação, e tendo como intuito pensar uma proposta de psicoterapia, conclui-se que o pensamento da existência, tal como desenvolvido por Haufniensis, proporciona elementos para a elaboração de uma proposta de psicoterapia que não se ocupe nem em julgar nem em teorizar, mas que sustente a existência como espaço onde tudo aparece como possibilidade.

  12. microRNAs in hematopoiesis

    NARCIS (Netherlands)

    Lazare, Seka S.; Wojtowicz, Edyta E.; Bystrykh, Leonid V.; de Haan, Gerald

    2014-01-01

    miRNAs have been implicated in all stages of hematopoiesis including maintenance of self-renewal of hematopoietic stem cells (HSCs) and differentiation into mature blood cells. Regulation by miRNAs is markedly intertwined with transcription factors. In this review, we highlight miRNAs shown to be

  13. Intracranial extramedullary hematopoiesis: a rare cause of headaches.

    Science.gov (United States)

    Singer, Adam; Quencer, Robert

    2014-01-01

    Ectopic bone marrow production, known as extramedullary hematopoiesis, may result in symptoms due to compression on normal structures. We present the multimodality imaging findings and subsequent management of a rare case of symptomatic extramedullary hematopoiesis within the calvarium. Case report. A 54-year-old male with a history of myelofibrosis and no previous diagnosis of a headache disorder presented to the emergency department with worsening severe bilateral headaches. A nonenhanced CT of the brain was performed and diffuse extra-axial nodular hyperdensities were visualized. MRI of the brain demonstrated diffuse extra-axial avidly enhancing nodular masses, dural thickening and marked susceptibility. No paravertebral masses, typical for extramedullary hematopoiesis, were present in the chest or abdomen. Although the clinical team considered a biopsy to confirm the diagnosis, we suggested a noninvasive confirmatory test. The subsequent Tc99m sulfur colloid scan corroborated the diagnosis. The patient was then referred to radiation oncology for treatment. In summary, extramedullary hematopoiesis is a hematologic compensatory disorder that rarely occurs within the CNS and may cause neurological compromise due to compression on underlying structures. The diagnosis can be made with noninvasive imaging and treated with low dose radiation therapy. Copyright © 2013 by the American Society of Neuroimaging.

  14. Dissection of vertebrate hematopoiesis using zebrafish thrombopoietin

    Czech Academy of Sciences Publication Activity Database

    Svoboda, Ondřej; Stachura, D.L.; Machoňová, Olga; Pajer, Petr; Brynda, Jiří; Zon, L.I.; Traver, D.; Bartůněk, Petr

    2014-01-01

    Roč. 124, č. 2 (2014), s. 220-228 ISSN 0006-4971 R&D Projects: GA ČR GAP305/10/0953 Grant - others:NIH(US) K01-DK087814-01A1; NIH(US) R01-DK074482 Keywords : Zebrafish * hematopoiesis * progenitors * thrombopoietin * erythropoietin Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.452, year: 2014

  15. Differential regulation of ANG2 and VEGF-A in human granulosa lutein cells by choriogonadotropin.

    Science.gov (United States)

    Pietrowski, D; Keck, C

    2004-04-01

    The growth and development of the corpus luteum after rupture of the follicle is a highly regulated process characterised by a rapid vascularization of the follicle surrounding granulosa cells. Vascularization is regulated by a large number of growth factors and cytokines whereas members of the angiopoietin family and VEGF-A are reported to play a principal role. The gonadotropic hormones luteinizing hormone and choriogonadotropin are reported to be essential for corpus luteum formation. In this study we investigated by RT PCR if the growth factors PGF, PDGF-A, PDGF-B, VEGF-A, VEGF-B, VEGF-C, VEGF-D, ANG1, ANG2, ANG3 and ANG4 are expressed in granulosa cells. We show the expression of VEGF-A, VEGF-B, PDGF-A, ANG1 and ANG2 in granulosa cells. Using RT-PCR and Real-Time PCR we demonstrate that angiopoietin 2 is downregulated in human granulosa cells in vitro after choriogonadotropin treatment whereas the expression of angiopoietin 1 is not significantly altered. The expression of VEGF on the RNA- and on the protein level was determined. It was shown that in granulosa cells VEGF is upregulated after choriogonadotropin treatment on the RNA level and that increasing concentrations of choriogonadotropin from 0 to 10 U/ml leads to an increasing amount of VEGF in the cell culture supernatants. The amount of VEGF in the supernatants reaches a plateau at 0.5 U/ml and is increased only slightly and not significantly after treatment of the cells with 10 U/ml choriogonadotropin compared to 0.5 U/ml. In total these findings suggests that in granulosa cells the mRNA of various growth factors is detectable by RT-PCR and that VEGF-A and ANG2 is regulated by the gonadotropic hormone choriogonadotropin. These findings may add impact on the hypothesis of choriogonadotropin as a novel angiogenic factor.

  16. Comparison of angiotensin II (Ang II) effects in the internal anal sphincter (IAS) and lower esophageal sphincter smooth muscles.

    Science.gov (United States)

    Rattan, Satish; Fan, Ya-Ping; Puri, Rajinder N

    2002-03-22

    Studies were performed to compare the actions of Ang II in the internal anal sphincter (IAS) vs. lower esophageal sphincter (LES) smooth muscles in vitro, in opossum and rabbit. Studies also were carried out in isolated smooth muscle cells. In opossum, Ang II produced no discernible effects in the IAS, but did produce a concentration-dependent contraction in the LES. Conversely, in the rabbit, while Ang II caused a modest response in the LES, it caused a significant contraction in the IAS. The contractile responses of Ang II in the opossum LES were mostly resistant to different neurohumoral antagonists but were antagonized by AT1 antagonist losartan. AT2 antagonist PD 123,319, rather than inhibiting, prolonged the contractile action of Ang II. The contractile actions of Ang II in the opossum LES were not modified by the tyrosine kinase inhibitors (genistein and tyrphostin 1 x 10(-6) M) but were partially attenuated by the PKC inhibitor H-7 (1 x 10(-6) M), Ca2+ channel blocker nicardipine (1 x 10(-5) M), Rho kinase inhibitor HA-1077 (1 x 10(-7) M) or p(44/42) MAP kinase inhibitor PD 98059 (5 x 10(-5) M). The combination of HA-1077 and H-7 did not cause an additive attenuation of Ang II responses. Western blot analyses revealed the presence of both AT1 and AT2 receptors. We conclude that Ang lI-induced contraction of sphincteric smooth muscle occurs primarily by the activation of AT1 receptors at the smooth muscle cells and involves multiple pathways, influx of Ca2+, and PKC, Rho kinase and p(44/42) MAP kinase.

  17. Angiotensin-(1-7)/Mas axis integrity is required for the expression of object recognition memory.

    Science.gov (United States)

    Lazaroni, Thiago L N; Raslan, Ana Cláudia S; Fontes, Walkiria R P; de Oliveira, Marilene L; Bader, Michael; Alenina, Natalia; Moraes, Márcio F D; Dos Santos, Robson A; Pereira, Grace S

    2012-01-01

    It has been shown that the brain has its own intrinsic renin-angiotensin system (RAS) and angiotensin-(1-7) (Ang-(1-7)) is particularly interesting, because it appears to counterbalance most of the Ang II effects. Ang-(1-7) exerts its biological function through activation of the G-protein-coupled receptor Mas. Interestingly, hippocampus is one of the regions with higher expression of Mas. However, the role of Ang-(1-7)/Mas axis in hippocampus-dependent memories is still poorly understood. Here we demonstrated that Mas ablation, as well as the blockade of Mas in the CA1-hippocampus, impaired object recognition memory (ORM). We also demonstrated that the blockade of Ang II receptors AT1, but not AT2, recovers ORM impairment of Mas-deficient mice. Considering that high concentrations of Ang-(1-7) may activate AT1 receptors, nonspecifically, we evaluate the levels of Ang-(1-7) and its main precursors Ang I and Ang II in the hippocampus of Mas-deficient mice. The Ang I and Ang II levels are unaltered in the whole hipocampus of MasKo. However, Ang-(1-7) concentration is increased in the whole hippocampus of MasKo mice, as well as in the CA1 area. Taken together, our findings suggest that the functionality of the Ang-(1-7)/Mas axis is essential for normal ORM processing. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. ANG II type 1 receptor antagonist irbesartan inhibits coronary angiogenesis stimulated by chronic intermittent hypoxia in neonatal rats

    Czech Academy of Sciences Publication Activity Database

    Rakusan, K.; Chvojková, Zuzana; Oliviero, P.; Ošťádalová, Ivana; Kolář, František; Chassagne, C.; Samuel, J. L.; Ošťádal, Bohuslav

    2007-01-01

    Roč. 292, č. 3 (2007), H1237-H1244 ISSN 0363-6135 R&D Projects: GA MŠk 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : angiogenesis neonatal rat * ANG II type 1 receptor antagonist heart * ischemic tolerance Subject RIV: ED - Physiology Impact factor: 3.973, year: 2007

  19. Alors ? méthode de français fondée sur l'approche des compétences : niveau B1 : CD et DVD inclus

    CERN Document Server

    Di Giura, Marcella

    2008-01-01

    Une nouvelle méthode qui propose des stratégies spécifiques pour l'acquisition des compétences communicatives, linguistiques et culturelles. Alors ? respecte les échelles de compétences des niveaux A1, A2 et B1 du CECRL.

  20. SlaVaComp: Konvertierungstool (= SlaVaComp Fonts Converter

    Directory of Open Access Journals (Sweden)

    Simon Skilevic

    2013-12-01

    Full Text Available Der vorliegende Beitrag informiert über ein Tool, das im Rahmen eines Freiburger Projekts zur historischen Korpuslinguistik entwickelt wurde und dazu dient, kirchenslavische Texte, die ohne Einsatz von Unicode digitalisiert wurden, ohne Verlust von Information bzw. Formatierung ins Unicode-Format zu überführen. Das Tool heißt SlaVaComp-Konvertierer. Es eignet sich für die Konvertierung aller idiosynkratischen Fonts und kann somit nicht nur in der Paläoslavistik, sondern in allen historisch arbeitenden Philologien eingesetzt werden. ____________________ This paper presents a fonts converter that was developed as a part of the Freiburg project on historical corpus linguistics. The tool named SlaVaComp-Konvertierer converts Church Slavonic texts digitized with non-Unicode fonts into the Unicode format without any loss of information contained in the original file and without damage to the original formatting. It is suitable for the conversion of all idiosyncratic fonts—not only Church Slavonic—and therefore can be used not only in Palaeoslavistic, but also in all historical and philological studies.

  1. Emergence of clonal hematopoiesis in the majority of patients with acquired aplastic anemia.

    Science.gov (United States)

    Babushok, Daria V; Perdigones, Nieves; Perin, Juan C; Olson, Timothy S; Ye, Wenda; Roth, Jacquelyn J; Lind, Curt; Cattier, Carine; Li, Yimei; Hartung, Helge; Paessler, Michele E; Frank, Dale M; Xie, Hongbo M; Cross, Shanna; Cockroft, Joshua D; Podsakoff, Gregory M; Monos, Dimitrios; Biegel, Jaclyn A; Mason, Philip J; Bessler, Monica

    2015-04-01

    Acquired aplastic anemia (aAA) is a nonmalignant disease caused by autoimmune destruction of early hematopoietic cells. Clonal hematopoiesis is a late complication, seen in 20-25% of older patients. We hypothesized that clonal hematopoiesis in aAA is a more general phenomenon, which can arise early in disease, even in younger patients. To evaluate clonal hematopoiesis in aAA, we used comparative whole exome sequencing of paired bone marrow and skin samples in 22 patients. We found somatic mutations in 16 patients (72.7%) with a median disease duration of 1 year; of these, 12 (66.7%) were patients with pediatric-onset aAA. Fifty-eight mutations in 51 unique genes were found primarily in pathways of immunity and transcriptional regulation. Most frequently mutated was PIGA, with seven mutations. Only two mutations were in genes recurrently mutated in myelodysplastic syndrome. Two patients had oligoclonal loss of the HLA alleles, linking immune escape to clone emergence. Two patients had activating mutations in key signaling pathways (STAT5B (p.N642H) and CAMK2G (p.T306M)). Our results suggest that clonal hematopoiesis in aAA is common, with two mechanisms emerging-immune escape and increased proliferation. Our findings expand conceptual understanding of this nonneoplastic blood disorder. Future prospective studies of clonal hematopoiesis in aAA will be critical for understanding outcomes and for designing personalized treatment strategies. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. CompHEP: developments and applications

    Science.gov (United States)

    Boos, E. E.; Bunichev, V. E.; Dubinin, M. N.; Ilyin, V. A.; Savrin, V. I.; CompHEP Collaboration

    2017-11-01

    New developments of the CompHEP package and its applications to the top quark and the Higgs boson physics at the LHC collider are reviewed. These developments were motivated mainly by the needs of experimental searches of DO (Tevatron) and CMS (LHC) collaborations where identification of the top quark and the Higgs boson in the framework of the Standard Model (SM) or possible extensions of the SM played an important role. New useful features of the CompHEP Graphics User Interface (GUI) are described.

  3. Plasma Ang2 and ADAM17 levels are elevated during clinical malaria; Ang2 level correlates with severity and expression of EPCR-binding PfEMP1

    DEFF Research Database (Denmark)

    Petersen, Jens E V; Mkumbaye, Sixbert I; Vaaben, Anna V

    2016-01-01

    The pathogenesis of Plasmodium falciparum malaria involves a complex interplay between parasite adhesion and inflammatory response that includes release of cytokines and activation of the endothelium with accompanying release of Angiopoitin 2 (Ang2) to the plasma. A-disintegrin and metalloprotein...

  4. CompTIA Network+ Review Guide Exam N10-005

    CERN Document Server

    Ferguson, Bill

    2012-01-01

    Fast, focused review for the latest CompTIA Network+ Exam N10-005 CompTIA's Network+ certification is the leading non-vendor networking certification in the world and has become the standard certification for networking professionals. Make sure you're ready for CompTIA's new Network+ certification (exam N10-005) with this new edition of Sybex's CompTIA Network+ Review Guide. This concise guide is efficiently organized by exam objectives and covers all five exam domains. The book also includes 50 chapter review questions, as well as access to two online practice exams, and much more. It's the p

  5. CompTIA Network+ Study Guide Exam N10-005

    CERN Document Server

    Lammle, Todd

    2012-01-01

    Todd Lammle's latest CompTIA Network+ Study Guide, now updated for the new exam! CompTIA's Network+ certification tells the world you have the skills to install, configure, and troubleshoot today's basic networking hardware peripherals and protocols. But first, you have to pass the exam! This detailed CompTIA Authorized study guide by networking guru Todd Lammle has everything you need to prepare for the CompTIA's new Network+Exam N10-005. All exam objectives are covered. He thoroughly explains key topics, offers plenty of practical examples, and draws upon his own invaluable 25+ years of netw

  6. The Differentiation Balance of Bone Marrow Mesenchymal Stem Cells Is Crucial to Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Jiang Wu

    2018-01-01

    Full Text Available Bone marrow mesenchymal stem cells (BMSCs, the important component and regulator of bone marrow microenvironment, give rise to hematopoietic-supporting stromal cells and form hematopoietic niches for hematopoietic stem cells (HSCs. However, how BMSC differentiation affects hematopoiesis is poorly understood. In this review, we focus on the role of BMSC differentiation in hematopoiesis. We discussed the role of BMSCs and their progeny in hematopoiesis. We also examine the mechanisms that cause differentiation bias of BMSCs in stress conditions including aging, irradiation, and chemotherapy. Moreover, the differentiation balance of BMSCs is crucial to hematopoiesis. We highlight the negative effects of differentiation bias of BMSCs on hematopoietic recovery after bone marrow transplantation. Keeping the differentiation balance of BMSCs is critical for hematopoietic recovery. This review summarises current understanding about how BMSC differentiation affects hematopoiesis and its potential application in improving hematopoietic recovery after bone marrow transplantation.

  7. Extramedullary paraspinal hematopoiesis in thalassemia: CT and MRI evaluation

    International Nuclear Information System (INIS)

    Tsitouridis, J.; Stamos, S.; Hassapopoulou, E.; Tsitouridis, K.; Nikolopoulos, P.

    1999-01-01

    We present a comparative CT and MRI study of the paraspinal extramedullary hematopoiesis in 32 thalassemic patients. The patients were classified into four groups according to the MRI and CT imaging findings. Active recent extramedullary paraspinal hematopoietic masses show soft tissue behavior in both CT and MRI. Older inactive masses reveal iron deposition or fatty replacement. Combined imaging findings of paraspinal extramedullary hematopoiesis revealed the phase of its evolution and the correct diagnosis

  8. Extramedullary paraspinal hematopoiesis in thalassemia: CT and MRI evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Tsitouridis, J.; Stamos, S.; Hassapopoulou, E.; Tsitouridis, K.; Nikolopoulos, P

    1999-04-01

    We present a comparative CT and MRI study of the paraspinal extramedullary hematopoiesis in 32 thalassemic patients. The patients were classified into four groups according to the MRI and CT imaging findings. Active recent extramedullary paraspinal hematopoietic masses show soft tissue behavior in both CT and MRI. Older inactive masses reveal iron deposition or fatty replacement. Combined imaging findings of paraspinal extramedullary hematopoiesis revealed the phase of its evolution and the correct diagnosis.

  9. [A case of cutaneous extramedullary hematopoiesis associated with idiopathic myelofibrosis].

    Science.gov (United States)

    Corella, F; Barnadas, M A; Bordes, R; Curell, R; Espinosa, I; Vergara, C; Alomar, A

    2008-05-01

    Cutaneous extramedullary hematopoiesis is a rare manifestation of chronic myeloproliferative processes, mainly chronic idiopathic myelofibrosis. In adults, it manifests as macules, papules, nodules, and ulcers on the trunk. The lesions usually appear soon after diagnosis and the possibility of a relationship between splenectomy and the appearance of extramedullary foci of hematopoiesis is still debated. Diagnosis is based on histopathology showing an infiltrate with different combinations of myeloid and erythroid cell precursors and megakaryocytes. Symptomatic treatment is provided alongside treatment of the underlying disease. We report a new case associated with chronic idiopathic myelofibrosis in which foci of cutaneous extramedullary hematopoiesis were observed 9 years after initial diagnosis. The lesions were progressive and the patient went on to develop acute myeloid leukemia.

  10. Race, Slavery, and the Re-evaluation of the T'ang Canon

    OpenAIRE

    Rutledge, Gregory E.

    2014-01-01

    In his article "Race, Slavery, and the Revaluation of the T'ang Canon" Gregory E. Rutledge re-evaluates—from the purview of African Diaspora literary studies—historiography that considers the place of East African slave lore in T'ang Dynasty fiction. Julie Wilensky's "The Magical Kunlun and 'Devil Slaves': Chinese Perceptions of Dark-skinned People and Africa before 1500" (2002), a revision of Chang Hsing-lang's "The Importation of Negro Slaves to China Under the T'ang Dynasty (A.D. 618-907)"...

  11. Potensi bambu swat (gigantochloa verticillata sebagai material karbon aktif untuk adsorbed natural gas (ANG

    Directory of Open Access Journals (Sweden)

    Dewa Ngakan Ketut Putra Negara

    2017-03-01

    Full Text Available Abstrak: Bambu merupakan material biomassa yang banyak diteliti, diproduksi sebagai karbon aktif dan diaplikasikan di berbagaibidang kehidupan. Namun sangat sedikit bahkan hampir tidak ditemukan referensi yang membahas kegunaan karbonaktif dari bambusebagai adsorbent untuk Adsorbed Natural Gas (ANG. Penelitian ini difokuskan untukmengkarakterisasai dan menevaluasi potensi bambu swat (Gigantochloa verticillata sebagai material dasar karbon aktifuntuk aplikasi ANG. Pengujian yang dilakukan meliputi uji proximate, uji ultimate, uji komposisi kimia dan pengamatanstruktur mikro. Hasil penelitian menunjukkan bahwa bambuswat memiliki kandungan lignin 22,9920%, selulosa44,2247%, volatile 88’32%, carbon 43,42%,ash 1,83%, silica (1,8664% dan nitrogen 1,7065%. Bambu swat memilikiikatan pembuluh yang terdiri atas satu ikatan pembuluh (xilem dan floem dan dua ikatan serat yang terletak di sebelahdalam dan luar dari ikatan pembuluh.Secara umum dapat dikatakan bahwa bamboo jenis ini memiliki kandungansellulosa, volatile dan karbon yang cukup tinggi serta ash, silica, hydrogen dan nitrogen yang rendah sehinggabambuswat sangat berpotensi digunakan sebagai material sumber karbon aktif.Kata kunci: Karbon aktif, bambu swat, ANG, lignin, sellulosa, analisa ultimate dan proximates Abstract: Bamboo is a biomass material widely researched, produced as activated carbon and applied in various life fields.However, very little or almost no references were found with regard to utilization of bamboo activated carbon asadsorbent for Adsorbed Natural Gas (ANG. This study is concerned to characterize and evaluate potency of bambooswat (Gigantochloa verticillata as aprecursor of activated carbon for ANG application. Examinations conducted wereproximate, ultimate, chemical composisition tests and microstructure observation. The results showed that bambooswathave a lignin content 22.9920%, cellulose 44.2247%, volatile 88.32%, carbon 43.42%, ash 1.83%, silica 1.8664% andnitrogen

  12. High-NaCl intake impairs dynamic autoregulation of renal blood flow in ANG II-infused rats

    DEFF Research Database (Denmark)

    Saeed, Aso; Dibona, Gerald F; Marcussen, Niels

    2010-01-01

    The aim of this study was to investigate dynamic autoregulation of renal blood flow (RBF) in ANG II-infused rats and the influence of high-NaCl intake. Sprague-Dawley rats received ANG II (250 ng·kg(-1)·min(-1) sc) or saline vehicle (sham) for 14 days after which acute renal clearance experiments...

  13. Hematopoiesis

    International Nuclear Information System (INIS)

    Testa, N.G.; Gale, R.P.

    1988-01-01

    Hematopoiesis critically assesses the implications of therapeutic or accidental exposure to cytotoxic drugs or radiation by analyzing their mechanisms of myelosuppression, - possible mutagenic action...capacity to induce chromosome abnormalities, - and effects on the immune system and other tissues. In addition, this reference: considers clinical and experimental observations on hemopoietic damage in the context of modern cell biology; evaluates the effects of treatment, natural history of the malignancy, and induced proliferative stress on the hemopoietic system; examines hemopoiesis within a framework relating to immunology, cytogenetics, and leukemogenesis; presents the subject in a logically developed sequence-building on fundamental biology and continuing through experimental data, clinical data, and future research trends; focuses on new research approaches to the therapy of malignancies; indicating possible approaches to correct long-term damage by control of cell proliferation and differentiation

  14. Single cell analysis of normal and leukemic hematopoiesis.

    Science.gov (United States)

    Povinelli, Benjamin J; Rodriguez-Meira, Alba; Mead, Adam J

    2018-02-01

    The hematopoietic system is well established as a paradigm for the study of cellular hierarchies, their disruption in disease and therapeutic use in regenerative medicine. Traditional approaches to study hematopoiesis involve purification of cell populations based on a small number of surface markers. However, such population-based analysis obscures underlying heterogeneity contained within any phenotypically defined cell population. This heterogeneity can only be resolved through single cell analysis. Recent advances in single cell techniques allow analysis of the genome, transcriptome, epigenome and proteome in single cells at an unprecedented scale. The application of these new single cell methods to investigate the hematopoietic system has led to paradigm shifts in our understanding of cellular heterogeneity in hematopoiesis and how this is disrupted in disease. In this review, we summarize how single cell techniques have been applied to the analysis of hematopoietic stem/progenitor cells in normal and malignant hematopoiesis, with a particular focus on recent advances in single-cell genomics, including how these might be utilized for clinical application. Copyright © 2017. Published by Elsevier Ltd.

  15. CompTIA Network+ Lab Manual

    CERN Document Server

    Skandier, Toby

    2012-01-01

    Gain street-smart skills in network administration Think of the most common and challenging tasks that network administrators face, then read this book and find out how to perform those tasks, step by step. CompTIA Network + Lab Manual provides an inside look into the field of network administration as though you were actually on the job. You'll find a variety of scenarios and potential roadblocks, as well as clearly mapped sections to help you prepare for the CompTIA Network+ Exam N10-005. Learn how to design, implement, configure, maintain, secure, and troubleshoot a network with this street

  16. Pulmonary Extramedullary Hematopoiesis in a Patient with Chronic Asthma Resembling Lung Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Massood Hosseinzadeh

    2012-01-01

    Full Text Available Background. Extramedullary hematopoiesis is most often seen in reticuloendothelial organs specially spleen, liver, or lymph nodes, and it is rarely seen in lung parenchyma. Almost all reported cases of pulmonary extramedullary hematopoiesis occurred following myeloproliferative disorders specially myelofibrosis. Other less common underlying causes are thalassemia syndromes and other hemoglobinopathies. There was not any reported case of pulmonary extramedullary hematopoiesis in asthmatic patients in the medical literature. Case. Here we reported a 65-year-old lady who was a known case of bronchial asthma with recent developed right lower lobe lung mass. Chest X-ray and CT studies showed an infiltrating mass resembling malignancy. Fine needle aspiration cytology of mass revealed pulmonary extramedullary hematopoiesis. The patient followed for 10 months with serial physical examination and laboratory evaluations which were unremarkable. Conclusion. Extramedullary hematopoiesis of lung parenchyma can be mistaken for lung cancer radiologically. Although previous reported cases occurred with myelofibrosis or hemoglobinopathies, we are reporting the first case of asthma-associated extramedullary hematopoiesis.

  17. Thermoluminescence authentication of T'ang and Han Dynasty pottery

    International Nuclear Information System (INIS)

    Price, D.M.

    1997-01-01

    More than 80 pieces of T'ang Dynasty and 40 Han Dynasty style ceramic wares have been analysed to determine the amount of thermoluminescence (TL) accumulated since the initial firing of the object and the level of the radiation flux which has created the TL. This paper presents a summary of the thermoluminescence analysis results. Approximately 60% of Han ceramics and 45% of the T'ang pottery authenticated have been shown to belong to periods other than that stylistically suggested. Items which have been found not to be of the anticipated antiquity generally fall into distinct age groups. Of the T'ang wares the most commonly copied item is found to be the horse and for the Han pieces, human figures and ewers/pots/vases represent the most frequently reproduced wares

  18. Perinatal Na+ Overload Programs Raised Renal Proximal Na+ Transport and Enalapril-Sensitive Alterations of Ang II Signaling Pathways during Adulthood

    Science.gov (United States)

    Cabral, Edjair V.; Vieira-Filho, Leucio D.; Silva, Paulo A.; Nascimento, Williams S.; Aires, Regina S.; Oliveira, Fabiana S. T.; Luzardo, Ricardo; Vieyra, Adalberto; Paixão, Ana D. O.

    2012-01-01

    Background High Na+ intake is a reality in nowadays and is frequently accompanied by renal and cardiovascular alterations. In this study, renal mechanisms underlying perinatal Na+ overload-programmed alterations in Na+ transporters and the renin/angiotensin system (RAS) were investigated, together with effects of short-term treatment with enalapril in terms of reprogramming molecular alterations in kidney. Methodology/Principal Findings Male adult Wistar rats were obtained from dams maintained throughout pregnancy and lactation on a standard diet and drinking water (control) or 0.17 M NaCl (saline group). Enalapril (100 mg/l), an angiotensin converting enzyme inhibitor, was administered for three weeks after weaning. Ninety day old offspring from dams that drank saline presented with proximal tubules exhibiting increased (Na++K+)ATPase expression and activity. Ouabain-insensitive Na+-ATPase activity remained unchanged but its response to angiotensin II (Ang II) was lost. PKC, PKA, renal thiobarbituric acid reactive substances (TBARS), macrophage infiltration and collagen deposition markedly increased, and AT2 receptor expression decreased while AT1 expression was unaltered. Early treatment with enalapril reduced expression and activity of (Na++K+)ATPase, partially recovered the response of Na+-ATPase to Ang II, and reduced PKC and PKA activities independently of whether offspring were exposed to high perinatal Na+ or not. In addition, treatment with enalapril per se reduced AT2 receptor expression, and increased TBARS, macrophage infiltration and collagen deposition. The perinatally Na+-overloaded offspring presented high numbers of Ang II-positive cortical cells, and significantly lower circulating Ang I, indicating that programming/reprogramming impacted systemic and local RAS. Conclusions/Significance Maternal Na+ overload programmed alterations in renal Na+ transporters and in its regulation, as well as severe structural lesions in adult offspring. Enalapril

  19. In vitro receptor autoradiography reveals angiotensin IL (ANG II) binding associated with sensory and motor components of the vagus

    International Nuclear Information System (INIS)

    Diz, D.I.; Barnes, K.L.; Ferrario, C.M.

    1986-01-01

    Specific, high affinity Ang II binding in the dog's dorsal medulla is concentrated in the area postrema, nucleus tractus solitarii (nTS) and dorsal motor nucleus of the vagus (dmnX). More recently Ang II binding sites were observed where bundles of vagal afferent fibers enter the dorsal medulla 6 mm rostral to obex and in the nodose ganglia and peripheral vagal nerves. Since Ang II binding in the nTS and dmnX overlies the distribution of vagal afferent fibers and efferent neurons, the effects of nodose ganglionectomy and cervical vagotomy on Ang II binding in the dorsal medulla were studied in rats and dogs using autoradiography after incubation of 14 μm coronal sections with 0.4 nM 125 I-Ang II. Nonspecific binding was determined in the presence of 1 μm unlabeled Ang II. Two weeks after unilateral nodose ganglionectomy Ang II binding sites were absent ipsilaterally in the region where vagal afferent fibers enter the dorsal medulla. In the nTS and dmnX, binding near obex was reduced, while more rostrally these nuclei were almost completely devoid of Ang II binding on the denervated side. After cervical vagotomy, the loss of binding was restricted to the ipsilateral dmnX. These data are the first to reveal that Ang II binding in the dorsal medulla requires an intact vagal system

  20. Expression profile analysis of aorta-gonad-mesonephros region-derived stromal cells reveals genes that regulate hematopoiesis

    International Nuclear Information System (INIS)

    Nagao, Kenji; Ohta, Takayuki; Hinohara, Atsushi; Tahara, Tomoyuki; Hagiwara, Tetsuya; Maeda, Yoshitake; Yoneya, Takashi; Sohma, Yoshiaki; Heike, Toshio; Nakahata, Tatsutoshi; Inagaki, Yoshimasa; Nishikawa, Mitsuo

    2008-01-01

    The aorta-gonad-mesonephros (AGM) region is involved in the generation and maintenance of the first definitive hematopoietic stem cells (HSCs). A mouse AGM-derived cell line, AGM-S3, was shown to support the development of HSCs. To elucidate the molecular mechanisms regulating early hematopoiesis, we obtained subclones from AGM-S3, one of which was hematopoiesis supportive (S3-A9) and the other one of which was non-supportive (S3-A7), and we analyzed their gene expression profiles by gene chip analysis. In the present study, we found that Glypican-1 (GPC1) was highly expressed in the supportive subclone AGM-S3-A9. Over-expression of GPC1 in non-supportive cells led to the proliferation of progenitor cells in human cord blood when cocultured with the transfected-stromal cells. Thus, GPC1 may have an important role in the establishment of a microenvironment that supports early events in hematopoiesis

  1. MED and PSACH COMP mutations affect chondrogenesis in chicken limb bud micromass cultures.

    Science.gov (United States)

    Roman-Blas, J; Dion, A S; Seghatoleslami, M R; Giunta, K; Oca, P; Jimenez, S A; Williams, C J

    2010-09-01

    Mutations in cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). We studied the effects of over-expression of wild type and mutant COMP on early stages of chondrogenesis in chicken limb bud micromass cultures. Cells were transduced with RCAS virus harboring wild type or mutant (C328R, PSACH; T585R, MED) COMP cDNAs and cultured for 3, 4, and 5 days. The effect of COMP constructs on chondrogenesis was assessed by analyzing mRNA and protein expression of several COMP binding partners. Cell viability was assayed, and evaluation of apoptosis was performed by monitoring caspase 3 processing. Over-expression of COMP, and especially expression of COMP mutants, had a profound affect on the expression of syndecan 3 and tenascin C, early markers of chondrogenesis. Over-expression of COMP did not affect levels of type II collagen or matrilin-3; however, there were increases in type IX collagen expression and sulfated proteoglycan synthesis, particularly at day 5 of harvest. In contrast to cells over-expressing COMP, cells with mutant COMP showed reduction in type IX collagen expression and increased matrilin 3 expression. Finally, reduction in cell viability, and increased activity of caspase 3, at days 4 and 5, were observed in cultures expressing either wild type or mutant COMP. MED, and PSACH mutations, despite displaying phenotypic differences, demonstrated only subtle differences in their cellular viability and mRNA and protein expression of components of the extracellular matrix, including those that interact with COMP. These results suggest that COMP mutations, by disrupting normal interactions between COMP and its binding partners, significantly affect chondrogenesis. (c) 2010 Wiley-Liss, Inc.

  2. Treatment with hydroxyurea in thalassemia intermedia with paravertebral pseudotumors of extramedullary hematopoiesis.

    Science.gov (United States)

    Cario, H; Wegener, M; Debatin, K-M; Kohne, E

    2002-08-01

    Excessive ineffective erythropoiesis in thalassemia intermedia may cause paravertebral pseudotumors of extramedullary hematopoiesis. Due to the proximity to the spinal canal, these paravertebral masses carry the risk of severe neurological damage. Treatment strategies include hypertransfusion, radiotherapy, and laminectomy. Hydroxyurea, stimulating fetal hemoglobin synthesis, may represent an alternative therapeutic approach. We report on a 26-year-old patient suffering from thalassemia intermedia with progressive anemia symptoms and presenting multiple intrathoracic paravertebral pseudotumors of extramedullary hematopoiesis. Hypertransfusion therapy and splenectomy were followed by regular transfusion (baseline hemoglobin 10 g/dl) and chelation with desferrioxamine. With this treatment, clinical symptoms disappeared, paravertebral hematopoietic masses did not progress, but severe hemosiderosis developed within a few years. Hydroxyurea therapy was initiated to increase the efficacy of erythropoiesis, thereby reducing the required transfusion volume but suppressing concomitantly further expansion of extramedullary hematopoiesis, and finally leading to a reduction of transfusional iron load. Treatment was started with 4 mg/kg per day and stepwise increased to 12.5 mg/kg per day. The fetal hemoglobin concentration increased from 4.5 to 5.5 g/dl after 1 year and to 9.9 g/dl after 2 years of treatment. The yearly transfusion volume was halved during the 1st year of treatment. At present, after 26 months of treatment, the patient has been transfusion-independent for 10 months. Serum ferritin levels decreased from 2844 to 1335 ng/ml. Size and shape of paravertebral hematopoietic pseudotumors remained stable. No side effects of hydroxyurea have been observed. In thalassemia intermedia patients with extramedullary hematopoiesis, hydroxyurea may lead to independence from regular transfusion therapy without further expansion of ectopic hematopoietic tissue.

  3. Thalassemia, extramedullary hematopoiesis, and spinal cord compression: A case report

    OpenAIRE

    Bukhari, Syed Sarmad; Junaid, Muhammad; Rashid, Mamoon Ur

    2016-01-01

    Background: Extramedullary hematopoiesis (EMH) refers to hematopoiesis outside of the medulla of the bone. Chronic anemia states such as thalassemia can cause hematopoietic tissue to expand in certain locations. We report a case of spinal cord compression due to recurrent spinal epidural EMH, which was treated with a combination of surgery and radiotherapy. Pakistan has one of the highest incidence and prevalence of thalassemia in the world. We describe published literature on diagnosis and m...

  4. Compartmental architecture and dynamics of hematopoiesis.

    Directory of Open Access Journals (Sweden)

    David Dingli

    Full Text Available BACKGROUND: Blood cell formation is maintained by the replication of hematopoietic stem cells (HSC that continuously feed downstream "compartments" where amplification and differentiation of cells occurs, giving rise to all blood lineages. Whereas HSC replicate slowly, committed cells replicate faster as they become more differentiated. METHODOLOGY/SIGNIFICANT FINDING: We propose a multi-compartment model of hematopoiesis, designed on the principle of cell flow conservation under stationary conditions. Cells lost from one compartment due to differentiation are replaced by cells from the upstream compartment. We assume that there is a constant relationship between cell input and output in each compartment and fix the single parameter of the model using data available for granulocyte maturation. We predict that approximately 31 mitotic events separate the HSC from the mature cells observed in the circulation. Besides estimating the number of compartments, our model allows us to estimate the size of each compartment, the rate of cell replication within each compartment, the mean time a given cell type contributes to hematopoiesis, the amplification rate in each compartment, as well as the mean time separating stem-cell replication and mature blood-cell formation. CONCLUSIONS: Despite its simplicity, the model agrees with the limited in vivo data available and can make testable predictions. In particular, our prediction of the average lifetime of a PIG-A mutated clone agrees closely with the experimental results available for the PIG-A gene mutation in healthy adults. The present elucidation of the compartment structure and dynamics of hematopoiesis may prove insightful in further understanding a variety of hematopoietic disorders.

  5. Alamandine acts via MrgD to induce AMPK/NO activation against Ang II hypertrophy in cardiomyocytes.

    Science.gov (United States)

    de Jesus, Itamar Couto Guedes; Scalzo, Sergio; Alves, Fabiana; Marques, Kariny; Rocha-Resende, Cibele; Bader, Michael; Santos, Robson A Souza; Guatimosim, Silvia

    2018-02-14

    The renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of cardiovascular diseases. New members of this system have been characterized and shown to have biologically relevant actions. Alamandine and its receptor MrgD are recently identified components of RAS. In the cardiovascular system alamandine actions included vasodilation, antihypertensive and anti-fibrosis effects. Currently, the actions of alamandine on cardiomyocytes are unknown. Here our goal was twofold: (1) to unravel the signaling molecules activated by the alamandine/MrgD axis in cardiomyocytes; (2) to evaluate the ability of this axis to prevent against Angiotensin II (Ang II)-induced hypertrophy. In cardiomyocytes from C57BL/6 mice, alamandine treatment induced an increase in nitric oxide (NO) production, which was blocked by D-Pro 7 -Ang-(1-7), a MrgD antagonist. This NO rise correlated with increased phosphorylation of AMPK. Alamandine induced NO production was preserved in Mas -/- myocytes, and lost in MrgD -/- cells. Binding of fluorescent-labeled alamandine was observed in wild-type cells, but it was dramatically reduced in MrgD -/- myocytes. We also assessed the consequences of prolonged alamandine exposure to cultured neonatal rat cardiomyocytes (NRCMs) treated with Ang II. Treatment of NRCMs with alamandine prevented Ang II-induced hypertrophy. Moreover, antihypertrophic actions of alamandine were mediated via MrgD and NO, since they could be prevented by D-Pro 7 -Ang-(1-7) or inhibitors of NO synthase or AMPK. β-alanine, a MrgD agonist, recapitulated alamandine's cardioprotective effects in cardiomyocytes. Our data show that alamandine via MrgD induces AMPK/NO signaling to counterregulate Ang II induced hypertrophy. These findings highlight the therapeutic potential of the alamandine/MrgD axis in the heart.

  6. Therapeutic effects of Fuzhenghuayu decoction on nonalcoholic steatohepatic fibrosis rats by regulating ACE-Ang Ⅱ-AT1R axis

    Directory of Open Access Journals (Sweden)

    Miao-miao HUO

    2018-04-01

    Full Text Available Objective To evaluate the influence of Fuzhenghuayu decoction on fibrotic liver tissue and angiotensin- converting enzyme- angiotensin Ⅱ- angiotensin Ⅱ 1 receptor (ACE-Ang Ⅱ-AT1R axis using a nonalcoholic fatty liver fibrosis rat model system. Methods Forty male Sprague-Dawley (SD rats were randomly divided into the following groups: normal control group, liver fibrosis model group, and liver fibrosis model Fuzhenghuayu drug intervention at low-dose [0.75g/(kg.d] group and high-dose [1.5g/(kg.d] group. Except the normal control group, the other three groups were fed high-fat diet for 24 weeks to induce nonalcoholic hepatic fibrosis model. The drug intervention was administered via oral-gastric irrigation once daily for 6 times per week over a 6-week period. The rats were sacrificed at the end of 6 weeks for serum and liver tissue collection. The levels of serum total cholesterol (TC, triglycerides (TG, alanine aminotransferase (ALT, aspartate aminotransferase (AST were measured by standard biochemical assays. The Ang Ⅱ contents of plasma and liver tissue were surveyed and evaluated by the radioimmunoassay method. Liver pathology was detected using HE staining and Masson trichrome staining. The mRNA and protein expressions of ACE, AT1R, α-smooth muscle actin (α-SMA in the liver tissue were evaluated with real time-PCR, immunohistochemical staining, respectively. Results Compared with the model group, the levels of serum ALT and AST in the low-dose group and high-dose group decreased conspicuously, especially in the high-dose group, with a statistically significant difference (P0.05; While the level of liver tissue Ang Ⅱ decreased significantly in the low-dose group and high-dose group than that in model group (P<0.05. Compared with the model group, the extent of pathological changes in hepatic tissues ameliorated after Fuzhenghuayu intervention according to HE and Masson staining, especially in the high-dose group. According to real

  7. CompTIA security+ review guide exam SY0-401

    CERN Document Server

    Stewart , James M

    2014-01-01

    Focused review for the CompTIA Security+ certification exam The CompTIA Security+ certification offers tremendous opportunities for IT professionals. For those who want to take their careers to the next level, CompTIA Security+ Review Guide: Exam SY0-401 is here to serve as a great resource for certification preparation. This concise, focused guide is easy to use and is organized by each exam objective for quick review and reinforcement of key topics. You'll find information on network security, compliance and operational security, and threats and vulnerabilities. Additionally, this indispensa

  8. CASP CompTIA Advanced Security Practitioner Study Guide Exam CAS-001

    CERN Document Server

    Gregg, Michael

    2012-01-01

    Get Prepared for CompTIA Advanced Security Practitioner (CASP) Exam Targeting security professionals who either have their CompTIA Security+ certification or are looking to achieve a more advanced security certification, this CompTIA Authorized study guide is focused on the new CompTIA Advanced Security Practitioner (CASP) Exam CAS-001. Veteran IT security expert and author Michael Gregg details the technical knowledge and skills you need to conceptualize, design, and engineer secure solutions across complex enterprise environments. He prepares you for aspects of the certification test that as

  9. Detection of Herpesvirus anguillae (AngHV-1) in European eel Anguilla anguilla (L.) originating from northern Poland-assessment of suitability of selected diagnostic methods.

    Science.gov (United States)

    Nguyen, Tuan Thuc; Jin, Yeonhwa; Kiełpińska, Jolanta; Bergmann, Sven M; Lenk, Matthias; Panicz, Remigiusz

    2017-11-01

    The Community Action Plan requests EU member states to implement measures that ensure the recovery of the severely depleted European eel stocks. One of the main threats is posed by Anguillid herpesvirus 1 (AngHV-1) leading to increased mortality in both wild and farmed eels. Following recommendations of the OIE to minimize the risk of obtaining false-negative results, the main aim of the study was to optimize diagnostic methods for AngHV-1 detection using conventional PCR, nested PCR and in situ hybridization assay. While 53.3% of the individual organ samples were tested positive for AngHV-1 by PCR, the additional virus analysis via nested PCR revealed that the actual prevalence was 93.3%. In the cell cultivation passages, a cytopathic effect was hardly found in the first two rounds. In the third passage onto cell cultures, a lytic CPE was detected. The identification and confirmation of the viruses obtained from cell cultures as well as directly from the organ tissues were proceeded by PCR, nested PCR and sequencing of the PCR products. While no positive signal was detectable in the first round by PCR using samples from the third cell culture passages, the nested PCR provided weak but visible positive signals. © 2017 John Wiley & Sons Ltd.

  10. CompTIA A+ complete lab manual

    CERN Document Server

    Pyles, James

    2012-01-01

    Boost your understanding of CompTIA A+ exam principles with practical, real-world exercises Designed to complement CompTIA A+ Complete Study Guide, this hands-on companion book takes you step by step through the tasks a PC technician is likely to face on any given day. It supports the theory explained in the test-prep guide with additional practical application, increasing a new PC technician's confidence and marketability. Various scenarios incorporate roadblocks that may occur on the job and explain ways to successfully complete the task at hand. In addition, each task is mapped to a specif

  11. Endothelial Activation: The Ang/Tie Axis in Sepsis

    Directory of Open Access Journals (Sweden)

    Aleksandra Leligdowicz

    2018-04-01

    Full Text Available Sepsis, a dysregulated host response to infection that causes life-threatening organ dysfunction, is a highly heterogeneous syndrome with no specific treatment. Although sepsis can be caused by a wide variety of pathogenic organisms, endothelial dysfunction leading to vascular leak is a common mechanism of injury that contributes to the morbidity and mortality associated with the syndrome. Perturbations to the angiopoietin (Ang/Tie2 axis cause endothelial cell activation and contribute to the pathogenesis of sepsis. In this review, we summarize how the Ang/Tie2 pathway is implicated in sepsis and describe its prognostic as well as therapeutic utility in life-threatening infections.

  12. Stochasticity and determinism in models of hematopoiesis.

    Science.gov (United States)

    Kimmel, Marek

    2014-01-01

    This chapter represents a novel view of modeling in hematopoiesis, synthesizing both deterministic and stochastic approaches. Whereas the stochastic models work in situations where chance dominates, for example when the number of cells is small, or under random mutations, the deterministic models are more important for large-scale, normal hematopoiesis. New types of models are on the horizon. These models attempt to account for distributed environments such as hematopoietic niches and their impact on dynamics. Mixed effects of such structures and chance events are largely unknown and constitute both a challenge and promise for modeling. Our discussion is presented under the separate headings of deterministic and stochastic modeling; however, the connections between both are frequently mentioned. Four case studies are included to elucidate important examples. We also include a primer of deterministic and stochastic dynamics for the reader's use.

  13. Vascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Michael G. Poulos

    2015-11-01

    Full Text Available Hematopoietic stem cells (HSCs inhabit distinct microenvironments within the adult bone marrow (BM, which govern the delicate balance between HSC quiescence, self-renewal, and differentiation. Previous reports have proposed that HSCs localize to the vascular niche, comprised of endothelium and tightly associated perivascular cells. Herein, we examine the capacity of BM endothelial cells (BMECs to support ex vivo and in vivo hematopoiesis. We demonstrate that AKT1-activated BMECs (BMEC-Akt1 have a unique transcription factor/cytokine profile that supports functional HSCs in lieu of complex serum and cytokine supplementation. Additionally, transplantation of BMEC-Akt1 cells enhanced regenerative hematopoiesis following myeloablative irradiation. These data demonstrate that BMEC-Akt1 cultures can be used as a platform for the discovery of pro-HSC factors and justify the utility of BMECs as a cellular therapy. This technical advance may lead to the development of therapies designed to decrease pancytopenias associated with myeloablative regimens used to treat a wide array of disease states.

  14. Cloud essentials CompTIA authorized courseware for exam CLO-001

    CERN Document Server

    Hausman, Kirk; Sampaio, Telmo

    2013-01-01

    CompTIA-Authorized courseware for the Cloud Essentials Exam (CLO-001) What better way to get up to speed on cloud computing than with this new book in the popular Sybex Essentials series? Cloud Essentials covers the basics of cloud computing and its place in the modern enterprise. Explore public and private clouds; contrast the ""as a service"" models for PaaS, SaaS, IaaS, or XaaS platforms; plan security; and more. In addition, the book covers the exam objectives for the both the CompTIA Cloud Essentials (Exam CLO-001) exam and the EXIN Cloud Computing Foundation (EX0-1

  15. The role of adenosine receptor agonists in regulation of hematopoiesis

    Czech Academy of Sciences Publication Activity Database

    Hofer, Michal; Pospíšil, Milan; Weiterová, Lenka; Hoferová, Zuzana

    2011-01-01

    Roč. 16, č. 1 (2011), s. 675-685 ISSN 1420-3049 R&D Projects: GA MO OVBIOFYZ20101; GA ČR(CZ) GA305/08/0158 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : adenosine receptors * hematopoiesis * myelosuppression Subject RIV: BO - Biophysics Impact factor: 2.386, year: 2011

  16. Hematopoiesis in 5-Fluorouracil-Treated Adenosine A(3) Receptor Knock-Out Mice

    Czech Academy of Sciences Publication Activity Database

    Hofer, Michal; Pospíšil, Milan; Dušek, L.; Hoferová, Zuzana; Komůrková, Denisa

    2015-01-01

    Roč. 64, č. 2 (2015), s. 255-262 ISSN 0862-8408 Institutional support: RVO:68081707 Keywords : Adenosine A(3) receptor knock-out mice * Hematopoiesis * 5-fluorouracil-induced hematotoxicity Subject RIV: BO - Biophysics Impact factor: 1.643, year: 2015

  17. Ang II-AT2R increases mesenchymal stem cell migration by signaling through the FAK and RhoA/Cdc42 pathways in vitro.

    Science.gov (United States)

    Xu, Xiu-Ping; He, Hong-Li; Hu, Shu-Ling; Han, Ji-Bin; Huang, Li-Li; Xu, Jing-Yuan; Xie, Jian-Feng; Liu, Ai-Ran; Yang, Yi; Qiu, Hai-Bo

    2017-07-12

    Mesenchymal stem cells (MSCs) migrate via the bloodstream to sites of injury and are possibly attracted by inflammatory factors. As a proinflammatory mediator, angiotensin II (Ang II) reportedly enhances the migration of various cell types by signaling via the Ang II receptor in vitro. However, few studies have focused on the effects of Ang II on MSC migration and the underlying mechanisms. Human bone marrow MSCs migration was measured using wound healing and Boyden chamber migration assays after treatments with different concentrations of Ang II, an AT1R antagonist (Losartan), and/or an AT2R antagonist (PD-123319). To exclude the effect of proliferation on MSC migration, we measured MSC proliferation after stimulation with the same concentration of Ang II. Additionally, we employed the focal adhesion kinase (FAK) inhibitor PF-573228, RhoA inhibitor C3 transferase, Rac1 inhibitor NSC23766, or Cdc42 inhibitor ML141 to investigate the role of cell adhesion proteins and the Rho-GTPase protein family (RhoA, Rac1, and Cdc42) in Ang II-mediated MSC migration. Cell adhesion proteins (FAK, Talin, and Vinculin) were detected by western blot analysis. The Rho-GTPase family protein activities were assessed by G-LISA and F-actin levels, which reflect actin cytoskeletal organization, were detected by using immunofluorescence. Human bone marrow MSCs constitutively expressed AT1R and AT2R. Additionally, Ang II increased MSC migration in an AT2R-dependent manner. Notably, Ang II-enhanced migration was not mediated by Ang II-mediated cell proliferation. Interestingly, Ang II-enhanced migration was mediated by FAK activation, which was critical for the formation of focal contacts, as evidenced by increased Talin and Vinculin expression. Moreover, RhoA and Cdc42 were activated by FAK to increase cytoskeletal organization, thus promoting cell contraction. Furthermore, FAK, Talin, and Vinculin activation and F-actin reorganization in response to Ang II were prevented by PD-123319 but

  18. Role of oxygen free radicals in the proliferation of myofibroblasts induced by AngII

    Directory of Open Access Journals (Sweden)

    Liying Wang

    2013-02-01

    Full Text Available Previous studies have demonstrated the important role of angiotension II (AngII in promoting proliferation of myofibroblasts (myoFbs and myocardial fibrosis. However, the underlying mechanisms and the role of oxygen free radicals in the proliferation of myofibroblasts induced by AngII are unclear. The present study was designed to shed light on this issue through exploration of AngII signaling pathways via in vitro experiments. Primary cultures of neonatal rat myoFbs were divided into five groups which were treated with AngII (10−8 to 10−6 M, AngII with the antioxidant N-acetyl-L-cysteine (NAC, or normal culture medium. We observed the proliferation of myoFbs as induced by AngII at different concentrations with MTT. Reactive oxygen species (ROS levels in myoFbs were detected by monitoring the fluorescence of 2′,7′-dichlorofluorescein. The contents and levels of oxygen free radicals (OH· in the three groups were detected by spectrophotometer, immunocytochemical staining, and confocal fluorescence. Western blot and image analysis were used to measure membrane translocation and expression of phospho-protein kinase Cα. MyoFbs incubated with AngII (10−8 to 10−6 M for 24 h increased their rate of proliferation, the content of OH·, and expression of ROS (P<0.01 vs. control group, whereas these parameters decreased in the presence of NAC. Immunocytochemistry, confocal fluorescence staining and image analysis showed that AngII could promote the translocation and expression of p-PKCα in membrane, and the antioxidant NAC blocked this increase (P<0.01. Western blot results also showed that NAC could inhibit the expression of p-PKCα.

  19. Ar ir CO2 plazma modifikuota aktyvintoji anglis acetono ir cikloheksano adsorbcijai

    Directory of Open Access Journals (Sweden)

    Piotr PIETROWSKI

    2012-06-01

    Full Text Available Žemos temperatūros plazmos poveikis, leidžiantis valdyti daugelio rūšių medžiagų, pvz., polimerų, metalų, anglies, paviršiaus savybes, šiuo metu yra tiriamas daugelyje mokslo sričių. Aktyvintoji  anglis (AC dėl savo fizikinių ir cheminių savybių naudojama kaip struktūrinis elementas dujų filtruose, kurie adsorbuodami daugelį skirtingų garų iš užteršto oro apsaugo kvėpavimo takus. Gerai žinoma, kad įvairios AC paviršiaus funkcinės grupės lemia jų hidrofobinę / hidrofilinę elgseną. Šame straipsnyje pristatomi pirminiai tyrimai, susiję su žemos temperatūros plazmos poveikiu komercinei aktyvintajai angliai. Aktyvintoji anglis buvo granuliuojama ir dedama į žemos temperatūros plazmos  rotacinę bandymų kamerą. Kamera buvo užpildoma atitinkamomis reaktyviosiomis dujomis. Plazmos poveikis buvo tiriamas nustatant aktyvintosios anglies paviršiaus dviejų pasirinktų rūšių organinių garų adsorbcijos izotermas, taip pat stebint šių garų adsorbcijos dinamiką ant dujų filtro, pagaminto iš plazma aktyvintos anglies. Remiantis gautais rezultatais, galima daryti išvadą, kad žemos temperatūros plazmos technologija gali būti taikoma aktyvintosios anglies savybėms pagerinti užtikrinant geresnę žemos temperatūros organinių garų adsorbciją.DOI: http://dx.doi.org/10.5755/j01.ms.18.2.1919

  20. Fps/Fes and Fer protein-tyrosinekinases play redundant roles in regulating hematopoiesis.

    Science.gov (United States)

    Senis, Yotis A; Craig, Andrew W B; Greer, Peter A

    2003-08-01

    The highly related protein-tyrosine kinases Fps (also called Fes) and Fer are sole members of a subfamily of kinases. In this study, knock-in mice harboring kinase-inactivating mutations in both fps and fer alleles were used to assess functional redundancy between Fps and Fer kinases in regulating hematopoiesis. Mice harboring kinase-inactivating mutations in fps and fer alleles were generated previously. Compound homozygous mice were bred that lack both Fps and Fer kinase activities and progeny were analyzed for potential defects in viability and fertility. Potential differences in hematopoiesis were analyzed by lineage analysis of bone marrow cells, peripheral blood counts, and hematopoietic progenitor cell colony-forming assays. Mice devoid of both Fps and Fer kinase activities were viable and displayed reduced fertility. Circulating levels of neutrophils, erythrocytes, and platelets were elevated in compound mutant mice compared to wild-type controls, suggesting that hematopoiesis is deregulated in the absence of Fps and Fer kinases. Compound mutant mice also showed reduced overall bone marrow cellularity, and lineage analysis revealed elevated CD11b(hi)Ly-6G(lo) myeloid cells, which may reflect increased granulocyte progenitors. Although no differences in the overall number of granulocyte/monocyte colony-forming progenitors were observed, qualitative differences in myeloid colonies from compound mutant mice suggested a role for Fps and Fer kinases in regulating cell-cell adhesion or a skewing in cellularity of colonies. Mice lacking both Fps and Fer kinase activities develop normally, show reduced fertility, and display defects in hematopoiesis, thus providing evidence for functional redundancy between Fps and Fer kinases in regulating hematopoiesis.

  1. A angústia de viver na cidade

    Directory of Open Access Journals (Sweden)

    Ana Claudia Aymoré Martins

    2015-04-01

    Full Text Available No romance Angústia, de Graciliano Ramos, a gradual dissolução psíquica de Luís da Silva tem uma relação intrínseca com as condições da vida urbana na modernidade, sendo a cidade referida ou semantizada ora como Babel, o caos urbano original, ora como Babilônia, a urbs corrompida pelo vício. Além disso, a recorrência de metáforas como a dos ratos (significando a degradação da vida, a corrupção da sexualidade ou o caráter predatório do materialismo burguês e a ênfase no estado de angústia revelam as interlocuções com conceitos filosóficos/psicológicos da Angst, tais como expressos em Freud, Kierkegaard e Heidegger.

  2. CompTIA Security+ Deluxe Study Guide Exam SY0-301

    CERN Document Server

    Dulaney, Emmett

    2011-01-01

    Get a host of extras with this Deluxe version including a Security Administration Simulator!  Prepare for CompTIA's new Security+ exam SY0-301 with this Deluxe Edition of our popular CompTIA Security+ Study Guide, 5th Edition. In addition to the 100% coverage of all exam essentials and study tools you'll find in the regular study guide, the Deluxe Edition gives you over additional hands-on lab exercises and study tools, three additional practice exams, author videos, and the exclusive Security Administration simulator. This book is a CompTIA Recommended product. Provides 100% coverage of all e

  3. CompTox Chemistry Dashboard webinar

    Science.gov (United States)

    The CompTox Chemistry Dashboard is part of a suite of dashboards developed by EPA to help evaluate the safety of chemicals. The dashboard provides access to a variety of information on over 700,000 chemicals currently in use. Within the application, users

  4. RED BLOOD CELL AND WHOLE BLOOD GLUTATHIONE REDOX STATUS IN ENDURANCE-TRAINED MEN FOLLOWING A SKI MARATHON

    Directory of Open Access Journals (Sweden)

    Eve Unt

    2008-09-01

    Full Text Available The aim of the present study was to evaluate the changes in glutathione redox ratio (GSSG·GSH-1 in red blood cells (RBCs and whole blood in well-trained men following a ski marathon. 16 male subjects (27.0 ± 4.7 yrs, 1.81 ± 0.06 m, 77.6 ± 9.6 kg, VO2max 66.2 ± 5.7 ml·kg-1·min-1 were examined before the competition (pre- COMP, after the competition (post-COMP and during an 18-hour recovery period (RECOV. There was a slight decrease in reduced glutathione (GSH in blood and in RBCs in post-COMP. During RECOV, the GSH level in blood was reduced, the GSH level in RBCs was significantly elevated (a statistically significant difference as compared to the pre-COMP level. The post-COMP GSSG·GSH-1 in full blood did not increase significantly, but its increase was statistically significant during the 18-hour recovery period. During the post-COMP and RECOV, the GSSG·GSH-1 in RBCs slightly decreased in comparison with the pre-COMP. Vitamin C concentration in serum increased in post-COMP (49% vs. pre- COMP and decreased to the baseline level during RECOV. In conclusion, our data show that acute exercise slightly increases the GSSG·GSH-1 in whole blood, while GSSG·GSH-1 in RBCs significantly decreases. Thus, exercise-related changes in the non-enzymatic components of the glutathione system (GSSG and GSH in whole blood and RBCs are not identical

  5. Dual inhibition of Ang-2 and VEGF receptors normalizes tumor vasculature and prolongs survival in glioblastoma by altering macrophages

    Science.gov (United States)

    Peterson, Teresa E.; Kirkpatrick, Nathaniel D.; Huang, Yuhui; Farrar, Christian T.; Marijt, Koen A.; Kloepper, Jonas; Datta, Meenal; Amoozgar, Zohreh; Seano, Giorgio; Jung, Keehoon; Kamoun, Walid S.; Vardam, Trupti; Snuderl, Matija; Goveia, Jermaine; Chatterjee, Sampurna; Batista, Ana; Muzikansky, Alona; Leow, Ching Ching; Xu, Lei; Batchelor, Tracy T.; Duda, Dan G.; Fukumura, Dai; Jain, Rakesh K.

    2016-01-01

    Glioblastomas (GBMs) rapidly become refractory to anti-VEGF therapies. We previously demonstrated that ectopic overexpression of angiopoietin-2 (Ang-2) compromises the benefits of anti-VEGF receptor (VEGFR) treatment in murine GBM models and that circulating Ang-2 levels in GBM patients rebound after an initial decrease following cediranib (a pan-VEGFR tyrosine kinase inhibitor) administration. Here we tested whether dual inhibition of VEGFR/Ang-2 could improve survival in two orthotopic models of GBM, Gl261 and U87. Dual therapy using cediranib and MEDI3617 (an anti–Ang-2–neutralizing antibody) improved survival over each therapy alone by delaying Gl261 growth and increasing U87 necrosis, effectively reducing viable tumor burden. Consistent with their vascular-modulating function, the dual therapies enhanced morphological normalization of vessels. Dual therapy also led to changes in tumor-associated macrophages (TAMs). Inhibition of TAM recruitment using an anti–colony-stimulating factor-1 antibody compromised the survival benefit of dual therapy. Thus, dual inhibition of VEGFR/Ang-2 prolongs survival in preclinical GBM models by reducing tumor burden, improving normalization, and altering TAMs. This approach may represent a potential therapeutic strategy to overcome the limitations of anti-VEGFR monotherapy in GBM patients by integrating the complementary effects of anti-Ang2 treatment on vessels and immune cells. PMID:27044097

  6. Peritoneal carcinomatosis-like implants of extramedullary hematopoiesis. An insolite occurrence during splenectomy for myelofibrosis

    Directory of Open Access Journals (Sweden)

    Marco Casaccia

    Full Text Available Introduction: Primary myelofibrosis (MF is a myeloproliferative neoplasm that results in debilitating constitutional symptoms, splenomegaly, and cytopenias. In patients with symptomatic splenomegaly, splenectomy remains a viable treatment option for MF patients with medically refractory symptomatic splenomegaly that precludes the use of ruxolitinib. Case presentation: We present the clinical case of a patient who was admitted to our Department to perform a splenectomy in MF as a therapeutic step prior to an allogeneic stem cell transplantation (ASCT. A laparotomic splenectomy and excision of whitish wide-spread peritoneal and omental nodulations was performed. There were no operative complications and the surgery was completed with minimal blood loss. The histopathological exam revealed an extramedullary hematopoiesis in both spleen and peritoneal nodules. Conclusion: In primary myelofibrosis it must always be kept in mind the possible presence of peritoneal implants of extramedullary hematopoiesis and ascites of reactive genesis. We report a rare case of peritoneal carcinomatosis-like implants of extramedullary hematopoiesis found at splenectomy for MF. Keywords: Myelofibrosis, Splenomegaly, Splenectomy, Extramedullary hematopoiesis

  7. A phase I trial of ANG1/2-Tie2 inhibitor trebaninib (AMG386) and temsirolimus in advanced solid tumors (PJC008/NCI♯9041).

    Science.gov (United States)

    Chiu, Joanne W; Hotte, Sebastien J; Kollmannsberger, Christian K; Renouf, Daniel J; Cescon, David W; Hedley, David; Chow, Sue; Moscow, Jeffrey; Chen, Zhuo; Perry, Meghan; Diaz-Padilla, Ivan; Tan, David; Hirte, Hal; McWhirter, Elaine; Chen, Helen; Siu, Lillian L; Bedard, Philippe L

    2016-02-01

    There is crosstalk between the ANG-Tie2 and the PI3K/Akt/mTOR pathways. Combined ANG1/2 and mTOR blockade may have additive anti-cancer activity. The combination of trebananib, an inhibitor of ANG1/2-Tie2 interaction, with temsirolimus was evaluated in patients with advanced solid tumors to determine tolerability, maximum tolerated dose (MTD), and preliminary antitumor activity. Patients were enrolled using 3 + 3 design, and were given intravenous trebananib and temsirolimus on Day 1, 8, 15 and 22 of a 28-day cycle. Dose limiting toxicities (DLTs) were evaluated during cycle 1. Peripheral blood was collected for evaluation of Tie2-expressing monocytes (TEMs) and thymidine phosphorylase (TP). Sparse pharmacokinetic (PK) sampling for trebananib drug levels was performed on Day 1 and 8 of cycle 2. Twenty-one patients were enrolled, 6 at dose level (DL) 1, 7 at DL -1, and 8 at DL -2. No effect of temsirolimus on trebananib PK was observed. The most common treatment-related adverse events (AEs) were: fatigue (81 %), edema (62 %), anorexia (57 %), nausea (52 %), rash (43 %) and mucositis (43 %). The most common grade ≥ 3 AEs included lymphopenia (28 %) and fatigue (28 %). The MTD was exceeded at DL-2. Of 18 response evaluable patients, 1 partial response was observed (ER+/HER2-/PIK3CA mutant breast cancer) and 4 patients had prolonged SD ≥ 24 weeks. No correlation with clinical benefit was observed with change in number TEMs or TP expression in TEMs with treatment. The MTD was exceeded at trebananib 10 mg/kg weekly and temsirolimus 20 mg weekly, with frequent overlapping toxicities including fatigue, edema, and anorexia.

  8. L’OCDE évalue les compétences des adultes

    OpenAIRE

    Bardi, Anne-Marie

    2014-01-01

    Une dizaine d’années après les premiers résultats du Programme international de suivi des acquis des élèves (PISA), l’Organisation de coopération et de développement économiques (OCDE) livre une étude sur les compétences des adultes de 16 à 65 ans. Ce nouveau Programme pour l’évaluation internationale des compétences des adultes (PIIAC) est conçu en cycles, dont le premier s’achève en 2013. Il vise à informer sur la maîtrise des compétences jugées indispensables pour évoluer dans un monde hyp...

  9. Clonal hematopoiesis in acquired aplastic anemia

    OpenAIRE

    Ogawa, Seishi

    2016-01-01

    Clonal hematopoiesis (CH) in aplastic anemia (AA) has been closely linked to the evolution of late clonal disorders, including paroxysmal nocturnal hemoglobinuria and myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML), which are common complications after successful immunosuppressive therapy (IST). With the advent of high-throughput sequencing of recent years, the molecular aspect of CH in AA has been clarified by comprehensive detection of somatic mutations that drive clonal evolut...

  10. Extramedullary hematopoiesis: a rare occurrence in the sinonasal tract.

    Science.gov (United States)

    Bizzoni, Andrea; Lombardi, Davide; Maroldi, Roberto; Incardona, Paolo; Nicolai, Piero

    2010-04-01

    Extramedullary hematopoiesis (EMH) is a systemic reaction to inadequate hematopoiesis. We report two exceedingly rare cases of EMH involving the paranasal sinuses. The first patient, a 30-year-old man, presented with a maxillary sinus mass. The lesion was excised by endoscopic surgery: definitive histology identified foci of EMH within an inflammatory fibromyxoid pseudotumor. The second case occurred in a 29-year-old man affected by intermediate beta-thalassemia. He was hospitalized with a diagnosis of sphenoid sinus mucocele secondary to an ethmoid lesion. The patient underwent endoscopic excision of the mass and drainage of the sphenoid mucocele. At definitive histology, a diagnosis of EMH was established. Herein, the presenting modalities, imaging profile, and treatment options of this rare EMH localization are reviewed. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  11. The correlation of serum PDGF and Ang-2 contents with atherosclerotic plaque features in patients with coronary heart disease

    Directory of Open Access Journals (Sweden)

    Yan-Bing Xi

    2017-04-01

    Full Text Available Objective: To study the correlation of serum PDGF and Ang-2 contents with atherosclerotic plaque features in patients with coronary heart disease. Methods: A total of 80 patients with coronary heart disease who were treated in our hospital between January 2013 and April 2016 were collected as the observation group, and 50 healthy subjects who received medical examination in our hospital during the same period were selected as the normal control group. Serum PDGF and Ang-2 contents of two groups of patients were detected, and the observation group were further divided into the high PDGF group and low PDGF group (n = 40 as well as the high Ang-2 group and low Ang-2 group (n = 40 according to the median of PDGF and Ang-2 contents. Ultrasonic contrast technology was used to assess the atherosclerotic plaque characteristics in patients with coronary heart disease. Results: Serum PDGF and Ang-2 contents of observation group were significantly higher than those of control group; ultrasound parameters P and AUC levels of high PDGF group were higher than those of low PDGF group while Tp and MTT levels were lower than those of low PDGF group; ultrasound parameters P and AUC levels of high Ang-2 group were higher than those of low Ang-2 group while Tp and MTT levels were lower than those of low Ang-2 group. Conclusion: Serum PDGF and Ang-2 contents increase in patients with coronary heart disease and are negatively correlated with the atherosclerotic plaque stability.

  12. Role of pp60(c-src) and p(44/42) MAPK in ANG II-induced contraction of rat tonic gastrointestinal smooth muscles.

    Science.gov (United States)

    Puri, Rajinder N; Fan, Ya-Ping; Rattan, Satish

    2002-08-01

    We examined the role of mitogen-activated protein kinase (p(44/42) MAPK) in ANG II-induced contraction of lower esophageal sphincter (LES) and internal anal sphincter (IAS) smooth muscles. Studies were performed in the isolated smooth muscles and cells (SMC). ANG II-induced changes in the levels of phosphorylation of different signal transduction and effector proteins were determined before and after selective inhibitors. ANG II-induced contraction of the rat LES and IAS SMC was inhibited by genistein, PD-98059 [a specific inhibitor of MAPK kinases (MEK 1/2)], herbimycin A (a pp60(c-src) inhibitor), and antibodies to pp60(c-src) and p(120) ras GTPase-activating protein (p(120) rasGAP). ANG II-induced contraction of the tonic smooth muscles was accompanied by an increase in tyrosine phosphorylation of p(120) rasGAP. These were attenuated by genistein but not by PD-98059. ANG II-induced increase in phosphorylations of p(44/42) MAPKs and caldesmon was attenuated by both genistein and PD-98059. We conclude that pp60(c-src) and p(44/42) MAPKs play an important role in ANG II-induced contraction of LES and IAS smooth muscles.

  13. Tennessee Comptroller of the Treasury (TN COMP)

    Data.gov (United States)

    Social Security Administration — The Tennessee Comptroller of the Treasury (TN COMP) uses SSA's assistance in administering the Tennessee Property Tax Rebate Program. SSA provides assistance through...

  14. Beta1 integrin is not essential for hematopoiesis but is necessary for the T cell-dependent IgM antibody response

    DEFF Research Database (Denmark)

    Brakebusch, Cord; Fillatreau, Simon; Potocnik, Alexandre J

    2002-01-01

    Several experimental evidences suggested that beta1 integrin-mediated adhesion of hematopoietic stem cells (HSC) is important for their function in the bone marrow (BM). Using induced deletion of the beta1 integrin gene restricted to the hematopoietic system, we show that beta1 integrin...... is not essential for HSC retention in the BM, hematopoiesis, and trafficking of lymphocytes. However, immunization with a T cell-dependent antigen resulted in virtually no IgM production and an increased secretion of IgG in mutant mice, while the response to a T cell-independent type 2 antigen showed decreases...

  15. The CompHP Core Competencies Framework for Health Promotion in Europe

    Science.gov (United States)

    Barry, Margaret M.; Battel-Kirk, Barbara; Dempsey, Colette

    2012-01-01

    Background: The CompHP Project on Developing Competencies and Professional Standards for Health Promotion in Europe was developed in response to the need for new and changing health promotion competencies to address health challenges. This article presents the process of developing the CompHP Core Competencies Framework for Health Promotion across…

  16. Somatic Mutations and Clonal Hematopoiesis in Aplastic Anemia.

    Science.gov (United States)

    Yoshizato, Tetsuichi; Dumitriu, Bogdan; Hosokawa, Kohei; Makishima, Hideki; Yoshida, Kenichi; Townsley, Danielle; Sato-Otsubo, Aiko; Sato, Yusuke; Liu, Delong; Suzuki, Hiromichi; Wu, Colin O; Shiraishi, Yuichi; Clemente, Michael J; Kataoka, Keisuke; Shiozawa, Yusuke; Okuno, Yusuke; Chiba, Kenichi; Tanaka, Hiroko; Nagata, Yasunobu; Katagiri, Takamasa; Kon, Ayana; Sanada, Masashi; Scheinberg, Phillip; Miyano, Satoru; Maciejewski, Jaroslaw P; Nakao, Shinji; Young, Neal S; Ogawa, Seishi

    2015-07-02

    In patients with acquired aplastic anemia, destruction of hematopoietic cells by the immune system leads to pancytopenia. Patients have a response to immunosuppressive therapy, but myelodysplastic syndromes and acute myeloid leukemia develop in about 15% of the patients, usually many months to years after the diagnosis of aplastic anemia. We performed next-generation sequencing and array-based karyotyping using 668 blood samples obtained from 439 patients with aplastic anemia. We analyzed serial samples obtained from 82 patients. Somatic mutations in myeloid cancer candidate genes were present in one third of the patients, in a limited number of genes and at low initial variant allele frequency. Clonal hematopoiesis was detected in 47% of the patients, most frequently as acquired mutations. The prevalence of the mutations increased with age, and mutations had an age-related signature. DNMT3A-mutated and ASXL1-mutated clones tended to increase in size over time; the size of BCOR- and BCORL1-mutated and PIGA-mutated clones decreased or remained stable. Mutations in PIGA and BCOR and BCORL1 correlated with a better response to immunosuppressive therapy and longer and a higher rate of overall and progression-free survival; mutations in a subgroup of genes that included DNMT3A and ASXL1 were associated with worse outcomes. However, clonal dynamics were highly variable and might not necessarily have predicted the response to therapy and long-term survival among individual patients. Clonal hematopoiesis was prevalent in aplastic anemia. Some mutations were related to clinical outcomes. A highly biased set of mutations is evidence of Darwinian selection in the failed bone marrow environment. The pattern of somatic clones in individual patients over time was variable and frequently unpredictable. (Funded by Grant-in-Aid for Scientific Research and others.).

  17. Apprentissage mobile et acquisition de la compétence pluriculturelle

    Directory of Open Access Journals (Sweden)

    LI Yue

    2016-11-01

    Full Text Available À mesure de l’évolution accélérée des technologies modernes, de nouveaux moyens d’apprentissage sont apparus dans le domaine de l’éducation, ce qui nous amène à nous demander comment en profiter en vue de favoriser l’enseignement/apprentissage du FLE. Dans cet article, nous prêtons une attention particulière à l’application de l’apprentissage mobile dans l’acquisition de la compétence pluriculturelle. Après une analyse de la compétence pluriculturelle, de l’apprentissage mobile, et de sa potentialité de développement en Chine, nous présentons les applications potentielles de l’apprentissage mobile dans l’acquisition de la compétence pluriculturelle des apprenants chinois de français.

  18. Development of nonfibrotic left ventricular hypertrophy in an ANG II-induced chronic ovine hypertension model

    DEFF Research Database (Denmark)

    Klatt, Niklas; Scherschel, Katharina; Schad, Claudia

    2016-01-01

    setting. Therefore, the aim of this study was to establish a minimally invasive ovine hypertension model using chronic angiotensin II (ANG II) treatment and to characterize its effects on cardiac remodeling after 8 weeks. Sheep were implanted with osmotic minipumps filled with either vehicle control (n...... = 7) or ANG II (n = 9) for 8 weeks. Mean arterial blood pressure in the ANG II-treated group increased from 87.4 ± 5.3 to 111.8 ± 6.9 mmHg (P = 0.00013). Cardiovascular magnetic resonance imaging showed an increase in left ventricular mass from 112 ± 12.6 g to 131 ± 18.7 g after 7 weeks (P = 0...... any differences in epicardial conduction velocity and heterogeneity. These data demonstrate that chronic ANG II treatment using osmotic minipumps presents a reliable, minimally invasive approach to establish hypertension and nonfibrotic LVH in sheep....

  19. AnGeLi: A Tool for the Analysis of Gene Lists from Fission Yeast

    Directory of Open Access Journals (Sweden)

    Danny A Bitton

    2015-11-01

    Full Text Available Genome-wide assays and screens typically result in large lists of genes or proteins. Enrichments of functional or other biological properties within such lists can provide valuable insights and testable hypotheses. To systematically detect these enrichments can be challenging and time-consuming, because relevant data to compare against query gene lists are spread over many different sources. We have developed AnGeLi (Analysis of Gene Lists, an intuitive, integrated web-tool for comprehensive and customized interrogation of gene lists from the fission yeast, Schizosaccharomyces pombe. AnGeLi searches for significant enrichments among multiple qualitative and quantitative information sources, including gene and phenotype ontologies, genetic and protein interactions, numerous features of genes, transcripts, translation, and proteins such as copy numbers, chromosomal positions, genetic diversity, RNA polymerase II and ribosome occupancy, localization, conservation, half-lives, domains and molecular weight among others, as well as diverse sets of genes that are co-regulated or lead to the same phenotypes when mutated. AnGeLi uses robust statistics which can be tailored to specific needs. It also provides the option to upload user-defined gene sets to compare against the query list. Through an integrated data submission form, AnGeLi encourages the community to contribute additional curated gene lists to further increase the usefulness of this resource and to get the most from the ever increasing large-scale experiments. AnGeLi offers a rigorous yet flexible statistical analysis platform for rich insights into functional enrichments and biological context for query gene lists, thus providing a powerful exploratory tool through which S. pombe researchers can uncover fresh perspectives and unexpected connections from genomic data. AnGeLi is freely available at: www.bahlerlab.info/AnGeLi

  20. Activation of adenosine receptors and inhibition of cyclooxygenases: two recent pharmacological approaches to modulation of radiation suppressed hematopoiesis

    International Nuclear Information System (INIS)

    Hofer, M.; Pospisil, M.; Vacek, A.; Hola, J.; Weiterova, L.; Streitova, D.; Znojil, V.

    2008-01-01

    Searching for drugs conforming to requirements for protection and/or treatment of radiation-induced damage belongs to the most important tasks of current radiobiology. In the Laboratory of Experimental Hematology, Institute of Biophysics, v.v.i., Academy of Sciences of the Czech Republic, Brno, Czech Republic, two original approaches for stimulation of radiation-suppressed hematopoiesis have been tested in recent years, namely activation of adenosine receptors and inhibition of cyclooxygenases. Non-selective activation of adenosine receptors, induced by combined administration of dipyridamole, a drug preventing adenosine uptake and supporting thus its extracellular receptor-mediated action, and adenosine monophosphate, an adenosine prodrug, has been found to stimulate hematopoiesis when the drugs were given either pre- or post-irradiation. When synthetic adenosine receptor agonists selective for individual adenosine receptor subtypes were tested, stimulatory effects in myelosuppressed mice have been found after administration of IB-MECA, a selective adenosine A3 receptor agonist. Non-selective cyclooxygenase inhibitors, inhibiting both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), indomethacin, diclofenac, or flurbiprofen, have been observed to act positively on radiation-perturbed hematopoiesis in sublethally irradiated mice. However, their undesirable gastrointestinal side effects have been found to negatively influence survival of lethally irradiated animals. Recently tested selective COX-2 inhibitor meloxicam, preserving protective action of COX-1-synthesized prostaglandins in the gastrointestinal tissues, has been observed to retain the hematopoiesis-stimulating effects of non-selective cyclooxygenase inhibitors and to improve the survival of animals exposed to lethal radiation doses. These findings bear evidence for the possibility to use selective adenosine A3 receptor agonists and selective COX-2 inhibitors in human practice for treatment of

  1. Extramedullary plasmacytoma involving perirenal space accompanied by extramedullary hematopoiesis and amyloid deposition.

    Science.gov (United States)

    Mimura, Rie; Kamishima, Tamotsu; Kubota, Kanako C; Nakano, Fumihito; Yabe, Ichiro; Sasaki, Hidenao; Maruyama, Satoru; Shinohara, Nobuo; Harris, Ardene A; Haga, Hironori; Shirato, Hiroki; Terae, Satoshi

    2010-05-01

    A 62-year-old man was referred to us after unsuccessful treatment of bilateral weakness in his upper and lower extremities with paresthesia in both lower extremities. Computed tomography (CT) revealed soft tissue masses in the left kidney along the capsule and paraaortic region that were of relatively low attenuation with accompanying granular calcifications. Pathological diagnosis of the biopsy specimen was extramedullary plasmacytoma accompanied by extramedullary hematopoiesis and amyloid deposition. Although the CT findings correlated well with the pathological results, the case was extremely atypical for extramedullary plasmacytoma in respect to location and the accompaniment with extramedullary hematopoiesis.

  2. CompTIA A+ complete study guide exams 220-801 and 220-802

    CERN Document Server

    Docter, Quentin; Skandier, Toby

    2012-01-01

    CompTIA Authorized, fully updated Study Guide for the leading IT certification: CompTIA A+ CompTIA A+ is the de facto certification for IT technicians. Some vendors even require employees to achieve certification as part of their job training. This book prepares you for both required exams: 220-801 and 220-802. Totally updated to cover the 2012 exams, this popular prep guide covers all the exam objectives. Readers will also have access to additional study tools, including the Sybex Test Engine with bonus practice exams, electronic flashcards, and a glossary of important terms in searchable PD

  3. Apatinib Inhibits Angiogenesis Via Suppressing Akt/GSK3β/ANG Signaling Pathway in Anaplastic Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Zhijian Jin

    2017-12-01

    Full Text Available Background/Aims: Anaplastic thyroid carcinoma (ATC is one of the most lethal human malignancies, and there is no efficient method to slow its process. Apatinib, a novel tyrosine kinase inhibitor (TKI, has been confirmed for its efficacy and safety in the treatment of advanced gastric carcinoma patients. However, the effects of Apatinib in ATC are still unknown. Methods: In this study, we explored the effects and mechanisms of Apatinib on tumor growth and angiogenesis in vitro and in vitro in ATC cells. Angiogenesis antibodies array was utilized to detect the expression of angiogenesis-related genes after Apatinib treatment in ATC cells. In addition, we used Akt activator, Akt inhibitor and GSK3β inhibitor to further study the mechanism for how Apatinib suppressed angiogenesis. Results: Apatinib treatment could suppress the growth of ATC cells in a dose- and time-dependent manner via inducing apoptosis and blocking cell cycle progression at G0/G1 phase. Moreover, Apatinib treatment decreased the expression of angiogenin (ANG and inhibited angiogenesis of ATC cells in vitro and in vitro. We further confirmed that recombinant human ANG (rhANG significantly abrogated Apatinib-mediated anti-angiogenic ability in ATC cells. Additionally, Apatinib treatment decreased the level of p-Akt and p-GSK3β. Moreover, the Apatinib-mediated decrease of ANG and anti-angiogenic ability were partly reversed when an Akt activator, SC79, was administered. Furthermore, the anti-angiogenic ability of Apatinib can be enhanced in the presence of Akt inhibitor, and the inhibition of GSK3β attenuated the anti-angiogenic ability of Apatinib. Conclusion: Our results demonstrated that Apatinib treatment inhibited tumor growth, and Apatinib-induced suppression of Akt/GSK3β/ANG signaling pathway may play an important role in the inhibition of angiogenesis in ATC, supporting a potential therapeutic approach for using Apatinib in the treatment of ATC.

  4. 27-Hydroxycholesterol induces hematopoietic stem cell mobilization and extramedullary hematopoiesis during pregnancy.

    Science.gov (United States)

    Oguro, Hideyuki; McDonald, Jeffrey G; Zhao, Zhiyu; Umetani, Michihisa; Shaul, Philip W; Morrison, Sean J

    2017-09-01

    Extramedullary hematopoiesis (EMH) is induced during pregnancy to support rapid expansion of maternal blood volume. EMH activation requires hematopoietic stem cell (HSC) proliferation and mobilization, processes that depend upon estrogen receptor α (ERα) in HSCs. Here we show that treating mice with estradiol to model estradiol increases during pregnancy induced HSC proliferation in the bone marrow but not HSC mobilization. Treatment with the alternative ERα ligand 27-hydroxycholesterol (27HC) induced ERα-dependent HSC mobilization and EMH but not HSC division in the bone marrow. During pregnancy, 27HC levels increased in hematopoietic stem/progenitor cells as a result of CYP27A1, a cholesterol hydroxylase. Cyp27a1-deficient mice had significantly reduced 27HC levels, HSC mobilization, and EMH during pregnancy but normal bone marrow hematopoiesis and EMH in response to bleeding or G-CSF treatment. Distinct hematopoietic stresses thus induce EMH through different mechanisms. Two different ERα ligands, estradiol and 27HC, work together to promote EMH during pregnancy, revealing a collaboration of hormonal and metabolic mechanisms as well as a physiological function for 27HC in normal mice.

  5. MetaComp: comprehensive analysis software for comparative meta-omics including comparative metagenomics.

    Science.gov (United States)

    Zhai, Peng; Yang, Longshu; Guo, Xiao; Wang, Zhe; Guo, Jiangtao; Wang, Xiaoqi; Zhu, Huaiqiu

    2017-10-02

    During the past decade, the development of high throughput nucleic sequencing and mass spectrometry analysis techniques have enabled the characterization of microbial communities through metagenomics, metatranscriptomics, metaproteomics and metabolomics data. To reveal the diversity of microbial communities and interactions between living conditions and microbes, it is necessary to introduce comparative analysis based upon integration of all four types of data mentioned above. Comparative meta-omics, especially comparative metageomics, has been established as a routine process to highlight the significant differences in taxon composition and functional gene abundance among microbiota samples. Meanwhile, biologists are increasingly concerning about the correlations between meta-omics features and environmental factors, which may further decipher the adaptation strategy of a microbial community. We developed a graphical comprehensive analysis software named MetaComp comprising a series of statistical analysis approaches with visualized results for metagenomics and other meta-omics data comparison. This software is capable to read files generated by a variety of upstream programs. After data loading, analyses such as multivariate statistics, hypothesis testing of two-sample, multi-sample as well as two-group sample and a novel function-regression analysis of environmental factors are offered. Here, regression analysis regards meta-omic features as independent variable and environmental factors as dependent variables. Moreover, MetaComp is capable to automatically choose an appropriate two-group sample test based upon the traits of input abundance profiles. We further evaluate the performance of its choice, and exhibit applications for metagenomics, metaproteomics and metabolomics samples. MetaComp, an integrative software capable for applying to all meta-omics data, originally distills the influence of living environment on microbial community by regression analysis

  6. Inhibitory effects of homeodomain-interacting protein kinase 2 on the aorta-gonad-mapharsen hematopoiesis

    International Nuclear Information System (INIS)

    Ohtsu, Naoki; Nobuhisa, Ikuo; Mochita, Miyuki; Taga, Tetsuya

    2007-01-01

    Definitive hematopoiesis starts in the aorta-gonad-mesonephros (AGM) region of the mouse embryo. Our previous studies revealed that STAT3, a gp130 downstream transcription factor, is required for AGM hematopoiesis and that homeodomain-interacting protein kinase 2 (HIPK2) phosphorylates serine-727 of STAT3. HIPK2 is a serine/threonine kinase known to be involved in transcriptional repression and apoptosis. In the present study, we examined the role of HIPK2 in hematopoiesis in mouse embryo. HIPK2 transcripts were found in fetal hematopoietic tissues such as the mouse AGM region and fetal liver. In cultured AGM cells, HIPK2 protein was detected in adherent cells. Functional analyses of HIPK2 were carried out by introducing wild-type and mutant HIPK2 constructs into AGM cultures. Production of CD45 + hematopoietic cells was suppressed by forced expression of HIPK2 in AGM cultures. This suppression required the kinase domain and nuclear localization signals of HIPK2, but the kinase activity was dispensable. HIPK2-overexpressing AGM-derived nonadherent cells did not form cobblestone-like colonies in cultures with stromal cells. Furthermore, overexpression of HIPK2 in AGM cultures impeded the expansion of CD45 low c-Kit + cells, which exhibit the immature hematopoietic progenitor phenotype. These data indicate that HIPK2 plays a negative regulatory role in AGM hematopoiesis in the mouse embryo

  7. Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals.

    Science.gov (United States)

    Sawai, Catherine M; Babovic, Sonja; Upadhaya, Samik; Knapp, David J H F; Lavin, Yonit; Lau, Colleen M; Goloborodko, Anton; Feng, Jue; Fujisaki, Joji; Ding, Lei; Mirny, Leonid A; Merad, Miriam; Eaves, Connie J; Reizis, Boris

    2016-09-20

    Hematopoietic stem cells (HSCs) sustain long-term reconstitution of hematopoiesis in transplantation recipients, yet their role in the endogenous steady-state hematopoiesis remains unclear. In particular, recent studies suggested that HSCs provide a relatively minor contribution to immune cell development in adults. We directed transgene expression in a fraction of HSCs that maintained reconstituting activity during serial transplantations. Inducible genetic labeling showed that transgene-expressing HSCs gave rise to other phenotypic HSCs, confirming their top position in the differentiation hierarchy. The labeled HSCs rapidly contributed to committed progenitors of all lineages and to mature myeloid cells and lymphocytes, but not to B-1a cells or tissue macrophages. Importantly, labeled HSCs gave rise to more than two-thirds of all myeloid cells and platelets in adult mice, and this contribution could be accelerated by an induced interferon response. Thus, classically defined HSCs maintain immune cell development in the steady state and during systemic cytokine responses. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Autosomal dominant precocious osteoarthropathy due to a mutation of the cartilage oligomeric matrix protein (COMP) gene: further expansion of the phenotypic variations of COMP defects

    Energy Technology Data Exchange (ETDEWEB)

    Kawaji, Hiroyuki [Department of Orthopaedic Surgery, Sanyudo Hospital, 6-1-219 Chuou, Yonezawa, Yamagata 992-0045 (Japan); Nishimura, Gen [Department of Radiology, Nasu Chuou Hospital, Tochigi (Japan); Watanabe, Sobei; Sasaki, Akira; Sano, Tokuhisa [Department of Orthopaedic Surgery, Tohoku Kohsei-Nenkin Hospital, Miyagi (Japan); Mabuchi, Akihiko; Ikeda, Toshiyuki; Ikegawa, Shiro [Laboratory for Bone and Joint Diseases, SNP Research Center, Tokyo (Japan); Ohashi, Hirofumi [Division of Medical Genetics, Saitama Children' s Medical Center, Saitama (Japan)

    2002-12-01

    We report on a Japanese family of four generations with an autosomal dominant precocious osteoarthropathy. The cardinal clinical manifestations of affected individuals were painful weight-bearing large joints, which started in late childhood or adolescence. The radiological hallmarks included coxa plana, mild epiphyseal dysplasia of the knee, and round talar domes with tibiotalar slant in childhood, which evolved into degenerative joint diseases in adulthood. The disease phenotype was cosegregated with a mutation of the cartilage oligomeric matrix protein (COMP) gene in the family members, who underwent molecular evaluation. COMP mutations have been reported in a mild form of multiple epiphyseal dysplasia (MED), Ribbing type, as well as allied disorders with more severe manifestations, such as MED Fairbank type and pseudoachondroplasia. Unlike previously reported cases with the Ribbing type, the present patients did not have short stature or brachydactyly. This report expands further the phenotypic variations of COMP defects. (orig.)

  9. Compétences pour les PME de l'Amérique centrale dans l'économie ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... compétences nécessaires; b) des recherches pour comprendre les modèles sociaux ... Il existe un lien bien documenté entre les compétences nécessaires pour ... Bien que ces compétences ne soient pas nécessairement axées sur les TIC, ...

  10. Intracranial Extramedullary Hematopoiesis in Beta-Thalassemia

    Energy Technology Data Exchange (ETDEWEB)

    Karki, Bivek; Xu, Yi Kai; Wu, Yuan Kui [Nan fang Hospital, Southern Medical University, Guangzhou (China); Tamrakar, Karuna [Zhujiang Hospital, Southern Medical University, Guangzhou (China)

    2012-03-15

    Extramedullary hematopoiesis (EMH) represents tumor-like proliferation of hemopoietic tissue which complicates chronic hemoglobinopathy. Intracranial EMH is an extremely rare occurrence. Magnetic resonance imaging (MRI) offers a precise diagnosis. It is essential to distinguish EMH from other extradural central nervous system tumors, because treatment and prognosis are totally different. Herein, we report the imaging findings of beta-thalassemia in a 13-year-old boy complaining of weakness of left side of the body and gait disturbance; CT and MRI revealed an extradural mass in the right temporoparietal region.

  11. Intracranial extramedullary hematopoiesis in beta-thalassemia.

    Science.gov (United States)

    Karki, Bivek; Xu, Yi-Kai; Tamrakar, Karuna; Wu, Yuan-Kui

    2012-01-01

    Extramedullary hematopoiesis (EMH) represents tumor-like proliferation of hemopoietic tissue which complicates chronic hemoglobinopathy. Intracranial EMH is an extremely rare occurrence. Magnetic resonance imaging (MRI) offers a precise diagnosis. It is essential to distinguish EMH from other extradural central nervous system tumors, because treatment and prognosis are totally different. Herein, we report the imaging findings of beta-thalassemia in a 13-year-old boy complaining of weakness of left side of the body and gait disturbance; CT and MRI revealed an extradural mass in the right temporoparietal region.

  12. Intracranial Extramedullary Hematopoiesis in Beta-Thalassemia

    International Nuclear Information System (INIS)

    Karki, Bivek; Xu, Yi Kai; Wu, Yuan Kui; Tamrakar, Karuna

    2012-01-01

    Extramedullary hematopoiesis (EMH) represents tumor-like proliferation of hemopoietic tissue which complicates chronic hemoglobinopathy. Intracranial EMH is an extremely rare occurrence. Magnetic resonance imaging (MRI) offers a precise diagnosis. It is essential to distinguish EMH from other extradural central nervous system tumors, because treatment and prognosis are totally different. Herein, we report the imaging findings of beta-thalassemia in a 13-year-old boy complaining of weakness of left side of the body and gait disturbance; CT and MRI revealed an extradural mass in the right temporoparietal region.

  13. Renal Bleeding Due to Extramedullary Hematopoiesis in a Patient With Chronic Myelogenous Leukemia

    Directory of Open Access Journals (Sweden)

    Stephanie Zettner

    2014-11-01

    Full Text Available Chronic myelogenous leukemia (CML is a myeloproliferative disorder that normally presents in middle-aged adults. Renal infiltration and extramedullary hematopoiesis in renal tissue has been rarely reported. This case report presents a patient with CML and renal insufficiency who developed gross hematuria. Efforts at controlling the hematuria led to a cascade of events propelled by the underlying disorder that ultimately led to a radical nephrectomy, multiorgan failure, and prolonged hospitalization. We suggest that management of gross hematuria in clinically stable patients with CML, suspected of having extramedullary hematopoiesis, should prioritize treatment of the myeloproliferative disorder over efforts to control bleeding.

  14. Renal Bleeding Due to Extramedullary Hematopoiesis in a Patient With Chronic Myelogenous Leukemia.

    Science.gov (United States)

    Zettner, Stephanie; Mistry, Sandeep G

    2014-11-01

    Chronic myelogenous leukemia (CML) is a myeloproliferative disorder that normally presents in middle-aged adults. Renal infiltration and extramedullary hematopoiesis in renal tissue has been rarely reported. This case report presents a patient with CML and renal insufficiency who developed gross hematuria. Efforts at controlling the hematuria led to a cascade of events propelled by the underlying disorder that ultimately led to a radical nephrectomy, multiorgan failure, and prolonged hospitalization. We suggest that management of gross hematuria in clinically stable patients with CML, suspected of having extramedullary hematopoiesis, should prioritize treatment of the myeloproliferative disorder over efforts to control bleeding.

  15. Les compétences évaluatives des formateurs d'enseignants

    OpenAIRE

    Jorro , Anne

    2005-01-01

    Dans cette communication, je présenterai une recherche exploratoire conduite auprès de formateurs d'enseignants dont les missions d'accompagnement des professeurs - stagiaires supposent des compétences évaluatives. Or, les formateurs d'enseignants entrevoient quasi naturellement la nécessité de gagner des compétences analytiques sur l'activité observée. Ces professionnels recourent plus volontiers à des moments d'analyse de pratiques et déclarent éprouver des difficultés à investir l'évaluati...

  16. CompTIA Security+ Review Guide Exam SY0-301

    CERN Document Server

    Stewart, James M

    2011-01-01

    Reinforce your preparation for CompTIA's new Security+ exam with this focused review tool Before you take CompTIA's new Security+ exam SY0-301, reinforce your learning with a thorough review and lots of practice. The new edition of this concise guide helps you do just that. It covers all six domains of exam SY0-301, all exam objectives, and includes a helpful "Exam Essentials" section after each domain to help you zero in on what you need to know for the exam. A companion CD offers additional study tools, including two complete practice exams, over a hundred electronic flashcards, and more.Rev

  17. Watching Dallas again 3 : Reassessing Ien Ang's Watching Dallas

    NARCIS (Netherlands)

    Heesakkers, Toon; van Hoof, Ward; Jager, Anne; Gilroy, Amanda

    2014-01-01

    This audience reception project performs an audience study of the first season of the new Dallas (2012–14). It draws on Ien Ang's Watching Dallas ([1982] 1985) to analyze the production of irony and nostalgia. We observe that the blend of ironic viewing and nostalgia results in a more ironic,

  18. Oposição e conflito na metapsicologia da angústia

    Directory of Open Access Journals (Sweden)

    Paulo de Carvalho Ribeiro

    Full Text Available Partindo da existência de diferentes graus e efeitos da angústia, busca-se estabelecer uma associação da angústia psicótica com a prevalência de uma oposição não conflitiva entre as forças pulsionais disruptivas e os elementos de ligação, transformados em exigências de um supereu tirânico e aberrante. Algumas idéias de Jean Laplanche sobre a exclusividade das forças de desligamento no inconsciente são criticadas, levando, assim, à discussão sobre o recalcamento, bem como a questões relacionadas com a presença do conflito nas neuroses e sua ausência nas psicoses.

  19. Each cell counts: Hematopoiesis and immunity research in the era of single cell genomics.

    Science.gov (United States)

    Jaitin, Diego Adhemar; Keren-Shaul, Hadas; Elefant, Naama; Amit, Ido

    2015-02-01

    Hematopoiesis and immunity are mediated through complex interactions between multiple cell types and states. This complexity is currently addressed following a reductionist approach of characterizing cell types by a small number of cell surface molecular features and gross functions. While the introduction of global transcriptional profiling technologies enabled a more comprehensive view, heterogeneity within sampled populations remained unaddressed, obscuring the true picture of hematopoiesis and immune system function. A critical mass of technological advances in molecular biology and genomics has enabled genome-wide measurements of single cells - the fundamental unit of immunity. These new advances are expected to boost detection of less frequent cell types and fuzzy intermediate cell states, greatly expanding the resolution of current available classifications. This new era of single-cell genomics in immunology research holds great promise for further understanding of the mechanisms and circuits regulating hematopoiesis and immunity in both health and disease. In the near future, the accuracy of single-cell genomics will ultimately enable precise diagnostics and treatment of multiple hematopoietic and immune related diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Peritoneal carcinomatosis-like implants of extramedullary hematopoiesis. An insolite occurrence during splenectomy for myelofibrosis.

    Science.gov (United States)

    Casaccia, Marco; Fornaro, Rosario; Frascio, Marco; Palombo, Denise; Stabilini, Cesare; Firpo, Emma; Gianetta, Ezio

    2017-01-01

    Primary myelofibrosis (MF) is a myeloproliferative neoplasm that results in debilitating constitutional symptoms, splenomegaly, and cytopenias. In patients with symptomatic splenomegaly, splenectomy remains a viable treatment option for MF patients with medically refractory symptomatic splenomegaly that precludes the use of ruxolitinib. We present the clinical case of a patient who was admitted to our Department to perform a splenectomy in MF as a therapeutic step prior to an allogeneic stem cell transplantation (ASCT). A laparotomic splenectomy and excision of whitish wide-spread peritoneal and omental nodulations was performed. There were no operative complications and the surgery was completed with minimal blood loss. The histopathological exam revealed an extramedullary hematopoiesis in both spleen and peritoneal nodules. In primary myelofibrosis it must always be kept in mind the possible presence of peritoneal implants of extramedullary hematopoiesis and ascites of reactive genesis. We report a rare case of peritoneal carcinomatosis-like implants of extramedullary hematopoiesis found at splenectomy for MF. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Impregnação de filmes do compósito de policarbonato (PC e sílica-gel (Si com corante fotocrômico em fluido supercrítico - DOI: 10.4025/actascitechnol.v32i1.1999

    Directory of Open Access Journals (Sweden)

    Fernanda de Almeida Fin de Lima

    2009-12-01

    Full Text Available O objetivo deste trabalho foi estudar a impregnação do corante fotocromático Reversacol Graphit® em filmes do compósito de policarbonato (PC e sílica-gel (Si, com a finalidade de obter aplicações em lentes fotocrômicas. Filmes de PC puros também foram impregnados nas mesmas condições, para verificar o efeito da adição de sílica-gel. Os filmes do compósito foram produzidos em proporções de Si:PC de 1:40 e 1:80 (m m-1, pelo método casting. Para a impregnação do corante Reversacol Graphit® nos filmes obtidos foi utilizado o processo supercrítico, pela sua eficiência e benefícios. A impregnação foi feita nos tempos de 15, 30, 45, 60, 90, 120, 150 e 180 min. A temperatura e a pressão adotadas foram de 60ºC e 120 bar. A quantidade de pigmento impregnado nos filmes de Si:PC – 1:40 e 1:80 (m m-1 foi de 29 e 23% de massa de corante por massa de compósito, respectivamente, e para o filme de PC puro foi de apenas 2,2% massa de corante por massa de compósito. Pelas análises térmicas, verificou-se que os filmes do compósito apresentaram maior estabilidade térmica. Pela técnica de microscopia eletrônica, observou-se que os filmes de PC puro e dos compósitos Si:PC – 1:40 e 1:80 (m m-1 apresentaram uma superfície lisa e homogênea.

  2. Ekvivalences pamata kategorijas , tulkojot specializētos tekstus ar angļu-latviešu un latviešu-angļu tulkojumu piemēriem

    OpenAIRE

    Saveļjevs, Jurijs

    2014-01-01

    Maģistra darbs ar nosaukumu „Ekvivalences pamata kategorijas, tulkojot specializētos tekstus, ar angļu-latviešu un latviešu-angļu tulkojumu piemēriem” ir veltīts dabiskās un virzītās, kā arī formālās un dinamiskās ekvivalences jēdzienu pētījumam. Darba teorētiskajā daļā tiek iztirzāta leksiski-sintaktisko valodas elementu ekvivalences jēdziena izcelsme un attīstība, tā pašreizējais stāvoklis un dažādu pētnieku tā redzējums. tāpat tiek izvērtētas ekvivalences jēdziena pamata kategorijas – dabi...

  3. Many layers of embryonic hematopoiesis: new insights into B-cell ontogeny and the origin of hematopoietic stem cells.

    Science.gov (United States)

    Hadland, Brandon; Yoshimoto, Momoko

    2018-04-01

    In adult hematopoiesis, the hematopoietic stem cell (HSC) sits at the top of a hierarchy of hematopoietic progenitors responsible for generating the diverse repertoire of blood and immune cells. During embryonic development, however, the initial waves of hematopoiesis provide the first functioning blood cells of the developing embryo, such as primitive erythrocytes arising in the yolk sac, independently of HSCs. In the field of developmental immunology, it has been recognized that some components of the immune system, such as B-1a lymphocytes, are uniquely produced during the embryonic and neonatal period, suggesting a "layered" development of immunity. Several recent studies have shed new light on the developmental origin of the layered immune system, suggesting complex and sometimes multiple contributions to unique populations of innate-like immune cells from both fetal HSCs and earlier HSC-independent progenitors. In this review, we will attempt to synthesize these studies to provide an integrated model of developmental hematopoiesis and layered immunity that may offer new insights into the origin of HSCs. Copyright © 2018 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  4. A new Brief computerized cognitive screening battery (CompCogs for early diagnosis of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Helenice Charchat Fichman

    Full Text Available Abstract Screening tests for early diagnosis of dementia are of great clinical relevance. The ideal test set must be brief and reliable, and should probe cognitive components impaired in Alzheimer's disease (AD. Objectives: To develop a new Computerized Cognitive Screening test (CompCogs, and to investigate its validity for the early diagnosis of AD, and evaluate its heuristic value in understanding the processing of information in AD. Methods: The computerized neuropsychological performance battery, originally including six tests, was applied in forty seven patients with probable mild AD and 97 controls matched for age and education. This computerized neuropsychological test battery, developed with MEL Professional, allows control of timing and order of stimuli presentation, as well as recording of response type and latency. A brief-screening version, CompCogs, was selected using the most discriminative neuropsychological test variables derived from logistic regression analysis. Full battery administration lasted about 40 minutes, while the CompCogs took only 15 minutes. Results: CompCogs included the Face test (correct response and Word and Forms with Short term memory tests (reaction time. CompCogs presented 91.8% sensitivity and 93.6% specificity for the diagnosis of AD using ROC analyses of AD diagnosis probability derived by logistic regression. Conclusions: CompCogs showed high validity for AD early diagnosis and, therefore, may be a useful alternative screening instrument.

  5. Deimanto tipo anglies nanokompozicinių (SiOx turinčių deimanto tipo anglies plėvelių struktūros, cheminės sudėties, savybių ir taikymo sričių apžvalga

    Directory of Open Access Journals (Sweden)

    Šarūnas MEŠKINIS

    2011-11-01

    Full Text Available Straipsnyje apžvelgiama dabartinė būklė nanokompozicinių deimanto tipo anglies plėvelių (SiOx turinčių deimanto tipo anglies dangų tyrimų srityje. Aptariami įvairūs šių dangų formavimo metodai bei sintezei naudojamos medžiagos. Įvairiais būdais ir įvairiomis sąlygomis užaugintų deimanto tipo anglies nanokompozicinių plėvelių cheminė sudėtis nagrinėta atsižvelgiant į tyrimų duomenis, gautus taikant skirtingus analizės metodus (rentgeno spindulių fotoelektronų spektroskopiją, infraraudonųjų spindulių spektroskopiją. Taip pat aprašyti skirtingų autorių siūlomi nanokompozicinių deimanto tipo anglies plėvelių struktūros modeliai. Apžvelgtos SiOx turinčių DTA plėvelių, suformuotų įvairiais būdais, mechaninės, optinės, elektrinės savybės bei plėvelių paviršiaus energija. Straipsnio pabaigoje aprašomos nanokompozicinių deimanto tipo anglies plėvelių dabartinės naudojimo sritys ir ateities perspektyvos.http://dx.doi.org/10.5755/j01.ms.17.4.770

  6. [Clinical features and COMP gene mutation in a family with a pseudoachondroplasia child].

    Science.gov (United States)

    Lu, Chun-Ting; Guo, Li; Zahng, Zhan-Hui; Lin, Wei-Xia; Song, Yuan-Zong; Feng, Lie

    2013-11-01

    This study aimed to report the clinical characteristics and COMP gene mutation of a family with pseudoachondroplasia (PSACH), a relatively rare spinal and epiphyseal dysplasia that is inherited as an autosomal dominant trait. Clinical information on a 5-year-2-month-old PSACH child and his parents was collected and analyzed. Diagnosis was confirmed by PCR amplification and direct sequencing of all the 19 exons and their flanking sequences of COMP gene, and the mutation was further ascertained by cloning analysis of exon 10. The child presented with short and stubby fingers, bow leg, short limb dwarfism and metaphysic broadening in long bone as well as lumbar lordosis. A mutation c.1048_1116del (p.Asn350_Asp372del) in exon 10, inherited from his father who did not demonstrate any phenotypic feature of PSACH, was detected in the child. PSACH was diagnosed definitively by means of COMP mutation analysis, on the basis of the child's clinical and imaging features. The non-penetrance phenomenon of COMP mutation was described for the first time in PSACH.

  7. Resistência de união de compósitos do tipo Bulk Fill: análise in vitro

    Directory of Open Access Journals (Sweden)

    Caroline de Farias CHARAMBA

    2017-03-01

    Full Text Available Resumo Introdução A classe dos compósitos Bulk-Fill tem obtido popularidade com a promessa de ser fotopolimerizado efetivamente em camadas de até quatro milímetros, fato que contrasta com os dois milímetros requisitados para os compósitos convencionais para manutenção da adesividade da restauração. Objetivo O objetivo deste estudo foi analisar a resistência de união à dentina de restaurações confeccionadas com compósitos do tipo Bulk-Fill. Material e método Foram utilizados 15 terceiros molares humanos, cuja superfície oclusal foi cortada e a dentina foi exposta. Esses elementos dentários foram divididos em três grupos conforme o material restaurador utilizado. O sistema adesivo usado foi o mesmo para todos os grupos. Posteriormente, os dentes restaurados foram cortados para originar palitos de aproximadamente 1 mm de largura, 1 mm de profundidade e 8 mm de altura, que foram fixados às garras do dispositivo de microtração. Foram utilizados dez palitos de cada dente, totalizando 50 palitos por grupo. Os dados de resistência de união à microtração foram expressos em megapascal (MPa. As fraturas foram analisadas em microscópio óptico. Os dados foram analisados através dos testes ANOVA e Tukey (p<0,05. Resultado Os três compósitos estudados diferiram estatisticamente entre si (p<0,000. Os compósitos Bulk-Fill apresentaram resistências de união semelhantes e superiores ao convencional (p<0,000. A fratura mais encontrada foi a mista, em todos os grupos. Conclusão Os compósitos Bulk-Fill apresentaram maiores valores de resistência de união com a técnica restauradora utilizada.

  8. Effects of deuteration on hematopoiesis in the mouse

    International Nuclear Information System (INIS)

    Adams, W.H.; Adams, D.G.

    1988-01-01

    Mice ingesting 30 to 50% D 2 O (heavy water, deuterium oxide) developed a dose-dependent depression of formed peripheral blood elements in 4 to 9 days. The principal mechanism of anemia and thrombocytopenia is impaired hematopoiesis. Despite pancytopenia in the peripheral blood, bone marrow cellularity and morphology remained normal. Upon replacement of D 2 O with tap water, platelet and neutrophil concentrations returned to normal within 48 to 72 hr. In contrast, blood lymphocyte concentrations remained low for several weeks. B-lymphocytes may be more affected by deuteration than other lymphocyte subsets. In vivo reticuloendothelial cell function, as assessed by 51 Cr-labeled sheep erythrocyte clearance, was unaffected by D 2 O. Although a dose-dependent decrease in fluid intake occurred during deuteration, hematocytopenia was not a consequence of dehydration. In view of the known kinetics of D 2 O in biological systems, the rapid response of myeloid elements to deuteration must be due primarily to the solvent (nonmetabolic) isotope effect. Prolonged deuteration has proven toxic when included in regimens for treatment of neoplasia, including leukemia, in animal models. The present study shows that modulation of hematopoiesis by D 2 O is possible without invoking the toxicities associated with prolonged deuteration

  9. Immediate loading versus immediate provisionalization of maxillary single-tooth replacements: a prospective randomized study with BioComp implants

    NARCIS (Netherlands)

    Lindeboom, Jerome A.; Frenken, Joost W.; Dubois, Leander; Frank, Michael; Abbink, Ingmar; Kroon, Frans H.

    2006-01-01

    PURPOSE: The aim of this prospective randomized study was to evaluate the clinical outcome of immediately loaded solid plasma sprayed (TPS) BioComp (BioComp Industries BV, Vught, The Netherlands) implants versus immediate provisionalized but non-loaded BioComp implants in the anterior and premolar

  10. Engraftment and reconstitution of hematopoiesis is dependent on VEGFR2 mediated regeneration of sinusoidal endothelial cells

    Science.gov (United States)

    Hooper, Andrea T.; Butler, Jason M.; Nolan, Daniel J; Kranz, Andrea; Iida, Kaoruko; Kobayashi, Mariko; Kopp, Hans-Georg; Shido, Koji; Petit, Isabelle; Yanger, Kilangsungla; James, Daylon; Witte, Larry; Zhu, Zhenping; Wu, Yan; Pytowski, Bronislaw; Rosenwaks, Zev; Mittal, Vivek; Sato, Thomas N.; Rafii, Shahin

    2011-01-01

    SUMMARY The phenotypic attributes and molecular determinants for the regeneration of bone marrow (BM) sinusoidal endothelial cells (SECs) and their contribution to hematopoiesis are unknown. We show that after myelosuppression VEGFR2 activation promotes reassembly of regressed SECs, reconstituting hematopoietic stem and progenitor cells (HSPCs). VEGFR2 and VEGFR3 expression are restricted to BM vasculature, demarcating a continuous network of VEGFR2+VEGFR3+Sca1− SECs and VEGFR2+VEGFR3−Sca1+ arterioles. While chemotherapy (5FU) and sublethal irradiation (650 rad) induce minor SEC regression, lethal irradiation (950 rad) induces severe regression of SECs requiring BM transplantation (BMT) for regeneration. Conditional deletion of VEGFR2 in adult mice blocks regeneration of SECs in sublethally irradiated animals, preventing hematopoietic reconstitution. Inhibition of VEGFR2 signaling in lethally irradiated wild type mice rescued with BMT severely impairs SEC reconstruction, preventing engraftment and reconstitution of HSPCs. Therefore, activation of VEGFR2 is critical for regeneration of VEGFR3+Sca1− SECs that are essential for engraftment and restoration of HSPCs and hematopoiesis. PMID:19265665

  11. Ingénierie des compétences et scénarisation pédagogique

    Directory of Open Access Journals (Sweden)

    Josianne Basque

    2007-01-01

    Full Text Available Cet article décrit un processus d’ingénierie éducative orienté compétences d’une activité d’autoévaluation et son intégration à un scénario pédagogique de cours à distance. Cette description est documentée par deux cas d’application dans un contexte de formation universitaire à distance. Le travail d’ingénierie utilise une approche en autogestion des compétences pour concevoir l’activité d’autoévaluation et l’instrumentaliser avec l’outil logiciel web d’autodiagnostic des compétences, appelé Compétences+. Cet acte d’ingénierie pédagogique porte l’attention de l’enseignant-concepteur sur une démarche centrée sur l’apprentissage dans une perspective d’autogestion des connaissances et de sa validation dans un usage en contexte isomorphe à une situation professionnelle réelle.

  12. The Acquisition of Quantity Contrasts in Guina-ang Bontok

    Science.gov (United States)

    Aoyama, Katsura; Reid, Lawrence A.

    2016-01-01

    This study reports on the acquisition of quantity contrasts in Guina-ang Bontok, an indigenous language spoken in the Philippines. Four-year-old and 5-year-old children's perception and production of quantity contrasts were examined using a pair of names that contrast in the quantity of the medial nasal. Frequencies of the quantity contrast were…

  13. 26 CFR 1.1336-1 - Basis of recovered property.

    Science.gov (United States)

    2010-04-01

    ... benefits by reason of the basis determined under subparagraph (1) of this paragraph, that it would be... recovered it has an unadjusted basis of $100. After $70 depreciation has been allowed on A, an allocation is sought which would give A an unadjusted basis of $60. Since this is less than the depreciation which is...

  14. Altered hematopoiesis in trisomy 21 as revealed through in vitro differentiation of isogenic human pluripotent cells

    Science.gov (United States)

    MacLean, Glenn A.; Menne, Tobias F.; Guo, Guoji; Sanchez, Danielle J.; Park, In-Hyun; Daley, George Q.; Orkin, Stuart H.

    2012-01-01

    Trisomy 21 is associated with hematopoietic abnormalities in the fetal liver, a preleukemic condition termed transient myeloproliferative disorder, and increased incidence of acute megakaryoblastic leukemia. Human trisomy 21 pluripotent cells of various origins, human embryionic stem (hES), and induced pluripotent stem (iPS) cells, were differentiated in vitro as a model to recapitulate the effects of trisomy on hematopoiesis. To mitigate clonal variation, we isolated disomic and trisomic subclones from the same parental iPS line, thereby generating subclones isogenic except for chromosome 21. Under differentiation conditions favoring development of fetal liver-like, γ-globin expressing, definitive hematopoiesis, we found that trisomic cells of hES, iPS, or isogenic origins exhibited a two- to fivefold increase in a population of CD43+(Leukosialin)/CD235+(Glycophorin A) hematopoietic cells, accompanied by increased multilineage colony-forming potential in colony-forming assays. These findings establish an intrinsic disturbance of multilineage myeloid hematopoiesis in trisomy 21 at the fetal liver stage. PMID:23045682

  15. Premature epiphyseal fusion and extramedullary hematopoiesis in thalassemia

    International Nuclear Information System (INIS)

    Colavita, N.; Orazi, C.; Danza, S.M.; Falappa, P.G.; Fabbri, R.

    1987-01-01

    The main skeletal abnormalities in β-thalassemia are widening of medullary spaces, rarefaction of bone trabeculae, thinning of cortical bone, and perpendicular periosteal spiculation. Premature epiphyseal fusion (PEF) and extramedullary hematopoiesis (EH) are found, though more rarely. The incidence of PEF and EH in 64 patients affected by β-thalassemia is reported. The different incidence of such complications in thalassemia major and intermedia is reported, and a possible correlation with transfusion regimen is also considered. (orig.)

  16. SlaVaComp Fonts Converter

    Directory of Open Access Journals (Sweden)

    Simon Skilevic

    2013-12-01

    Full Text Available This paper presents a fonts converter that was developed as a part of the Freiburg project on historical corpus linguistics. The tool named SlaVaComp-Konvertierer converts Church Slavonic texts digitized with non-Unicode fonts into the Unicode format without any loss of information contained in the original file and without damage to the original formatting. It is suitable for the conversion of all idiosyncratic fonts—not only Church Slavonic—and therefore can be used not only in Palaeoslavistic, but also in all historical and philological studies.

  17. ANG coal gasification project management control system report. [Great Plains project

    Energy Technology Data Exchange (ETDEWEB)

    1981-01-01

    Much time, money and effort has been spent in the forefront of this project for project controls. The work breakdown structure for the systems has been custom designed. The systems, both manual and computerized, have been well scrutinized and chosen by ANG to represent the most cost effective and efficient way of controlling a project the magnitude of $1.5 billion. These systems have been developed in a manner so that information can be gathered as detailed or as summarized as necessary, and in the most timely and expeditious ways.

  18. SyGuS-Comp 2016: Results and Analysis

    Directory of Open Access Journals (Sweden)

    Rajeev Alur

    2016-11-01

    Full Text Available Syntax-Guided Synthesis (SyGuS is the computational problem of finding an implementation f that meets both a semantic constraint given by a logical formula φ in a background theory T, and a syntactic constraint given by a grammar G, which specifies the allowed set of candidate implementations. Such a synthesis problem can be formally defined in SyGuS-IF, a language that is built on top of SMT-LIB. The Syntax-Guided Synthesis Competition (SyGuS-Comp is an effort to facilitate, bring together and accelerate research and development of efficient solvers for SyGuS by providing a platform for evaluating different synthesis techniques on a comprehensive set of benchmarks. In this year's competition we added a new track devoted to programming by examples. This track consisted of two categories, one using the theory of bit-vectors and one using the theory of strings. This paper presents and analyses the results of SyGuS-Comp'16.

  19. Hydroxychloroquine induces inhibition of collagen type II and oligomeric matrix protein COMP expression in chondrocytes

    Directory of Open Access Journals (Sweden)

    Tao Li

    2016-06-01

    Full Text Available The aim of this study was to investigate the effect of hydroxychloroquine on the level of collagen type II and oligomeric matrix protein COMP expression in chondrocytes of knee osteoarthritis. The rate of growth in cartilage cells was analyzed using MTT assay whereas the Col-2 and COMP expression levels were detected by RT-PCR and Western blotting analyses. For the determination of MMP-13 expression, ELISA test was used. The results revealed no significant change in the rate of cartilage cell proliferation in hydroxychloroquine-treated compared to untreated cells. Hydroxychloro-quine treatment exhibited concentration- and time-dependent effect on the inhibition of collagen type II and COMP expression in chondrocytes. However, its treatment caused a significant enhancement in the expression levels of MMP-13 compared to the untreated cells. Therefore, hydroxychloro-quine promotes expression of MMP-13 and reduces collagen type II and COMP expression levels in chondrocytes without any significant change in the growth of cells.

  20. Informatisation de la gestion des compétences : évaluation de la démarche dans une collectivité territoriale

    OpenAIRE

    Bachelet, Catherine; Galey, Béatrice

    2013-01-01

    Notion répandue mais difficile à cerner, la gestion des compétences peut être définie comme une instrumentation sur laquelle les acteurs professionnels de la GRH se fondent pour instruire leurs décisions de gestion (Gilbert, 2003). Constituée d'un « ensemble de pratiques visant à acquérir, stimuler et réguler les compétences des salariés » (Defélix et Retour, 2003), elle permet d'améliorer l'adéquation entre les compétences nécessaires et les compétences disponibles, pour optimiser la compéti...

  1. miRNAs in Normal and Malignant Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Ryutaro Kotaki

    2017-07-01

    Full Text Available Lineage specification is primarily regulated at the transcriptional level and lineage-specific transcription factors determine cell fates. MicroRNAs (miRNAs are 18–24 nucleotide-long non-coding RNAs that post-transcriptionally decrease the translation of target mRNAs and are essential for many cellular functions. miRNAs also regulate lineage specification during hematopoiesis. This review highlights the roles of miRNAs in B-cell development and malignancies, and discusses how miRNA expression profiles correlate with disease prognoses and phenotypes. We also discuss the potential for miRNAs as therapeutic targets and diagnostic tools for B-cell malignancies.

  2. Ex vivo tools for the clonal analysis of zebrafish hematopoiesis

    Czech Academy of Sciences Publication Activity Database

    Svoboda, Ondřej; Stachura, D.L.; Machoňová, Olga; Zon, L.I.; Traver, D.; Bartůněk, Petr

    2016-01-01

    Roč. 11, č. 5 (2016), s. 1007-1020 ISSN 1754-2189 R&D Projects: GA MŠk LO1419; GA ČR GA16-21024S Institutional support: RVO:68378050 Keywords : stem-cells * in-vitro * vertebrate hematopoiesis * transgenic zebrafish * progenitor cells * danio-rerio * fish * thrombopoietin * identification * specification Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.032, year: 2016

  3. Efeito do tratamento alcalino de fibras de Curauá sobre as propriedades de compósitos de matriz biodegradável

    Directory of Open Access Journals (Sweden)

    Lílian Vanessa Rossa Beltrami

    2014-06-01

    Full Text Available Neste trabalho avaliou-se a influência do tratamento alcalino das fibras de curauá, nas concentrações de 1, 5 e 10%(m/v de NaOH, nas propriedades dos compósitos com matriz de PHBV e 20% m/m de fibras de curauá. Os compósitos foram moldados por extrusão e injeção e avaliadas suas as propriedades morfológicas, térmicas e mecânicas. Os resultados de FTIR mostraram que o tratamento alcalino promoveu modificações na estrutura das fibras de curauá, comprovadas pela remoção da hemicelulose e da lignina, evidenciadas pela ausência das bandas típicas destes compostos. Nos compósitos com fibras de curauá tratadas com solução de NaOH na concentração de 5% apresentaram um aumento de 30% na resistência à flexão e 12% na resistência ao impacto, quando comparados aos compósitos com fibras sem tratamento. Estes resultados indicam que o tratamento alcalino promoveu uma melhoria na adesão das fibras na matriz, o que melhorou significativamente as propriedades mecânicas dos compósitos.

  4. Suppression of hepatic hematopoiesis with radioactive gold (198Au)

    International Nuclear Information System (INIS)

    Turner, A.R.; Gummerman, L.W.; Boggs, D.R.

    1985-01-01

    A patient with idiopathic myelofibrosis of some 20 yr duration developed esophageal varices and ascites. No explanation for increased portal pressure other than hepatic hematopoiesis was found. Consequently, a trial of cobalt irradiation to the liver was undertaken with definite but transient decrease in ascites. Subsequently, two courses of radioactive colloidal gold were given, again with definite but transient beneficial effects on the degree of ascites. This latter benefit occurred without suppression of marrow function

  5. Influence on radiogenic alterations in hematopoiesis - Situation and possibilities

    International Nuclear Information System (INIS)

    Kehrberg, G.; Rose, H.; Saul, G.; Riessbeck, K.H.

    1985-01-01

    Radiogenic alterations of hematopoiesis are a main topic in radiobiological investigations. By further elucidation of the regulatory mechanisms possibly follow new starting points to accelerate the regeneration of stem cells, still capable of proliferating, or differentiation of most endangered and nearly irretrievable cell populations by drugs. The present state is discussed concerning the application of anabolics, endotoxins, thymic extracts, cyanoethylurea, and lithium carbonate as well as parenteral nutrition and competition of stem cells. (author)

  6. Influence on radiogenic alterations in hematopoiesis - Situation and possibilities

    Energy Technology Data Exchange (ETDEWEB)

    Kehrberg, G; Rose, H; Saul, G; Riessbeck, K H [Humboldt-Universitaet, Berlin (German Democratic Republic). Bereich Medizin (Charite)

    1985-01-01

    Radiogenic alterations of hematopoiesis are a main topic in radiobiological investigations. By further elucidation of the regulatory mechanisms possibly follow new starting points to accelerate the regeneration of stem cells, still capable of proliferating, or differentiation of most endangered and nearly irretrievable cell populations by drugs. The present state is discussed concerning the application of anabolics, endotoxins, thymic extracts, cyanoethylurea, and lithium carbonate as well as parenteral nutrition and competition of stem cells.

  7. Aris Angelis (1954-2003)

    CERN Multimedia

    2003-01-01

    The value of a person is recognized more by what he leaves behind. Aris Angelis has left a plethora of people: teachers, friends, colleagues, associates, acquaintances, all of whom were shocked and devastated by his untimely and "unjust" departure. Some thought of him as their "mentor" during their crucial and difficult first steps in science... Some others as the ever-giving friend, who put the "common good" in front of himself... Others feel an "unpaid debt" to him, who left so soon and so unexpected... Some feel an enormous loss and a huge vacuum left behind where he was... Others had looked forward to working with him in his new scientific environment... But, ALL of us shall remember Aris with love and joy for what he was and what he has given and left to us. Apostolos D. Panagiotou (Teacher, colleague & friend) Aris was very sensitive to the need for science communication. A CERN guide since 1999, he took part in all special events, such as open days and the Oracle de Delphi, always with the same ...

  8. Radar Precoder Design for Spectral Coexistence with Coordinated Multi-point (CoMP) System

    OpenAIRE

    Mahal, Jasmin A.; Khawar, Awais; Abdelhadi, Ahmed; Clancy, T. Charles

    2015-01-01

    This paper details the design of precoders for a MIMO radar spectrally coexistent with a MIMO cellular network. We focus on a coordinated multi-point (CoMP) system where a cluster of base stations (BSs) coordinate their transmissions to the intended user. The radar operates in two modes, interference-mitigation mode when it avoids interference with the CoMP system and cooperation mode when it exchanges information with it. Using either the conventional Switched Null Space Projection (SNSP) or...

  9. Oral feeding with polyunsaturated fatty acids fosters hematopoiesis and thrombopoiesis in healthy and bone marrow-transplanted mice.

    Science.gov (United States)

    Limbkar, Kedar; Dhenge, Ankita; Jadhav, Dipesh D; Thulasiram, Hirekodathakallu V; Kale, Vaijayanti; Limaye, Lalita

    2017-09-01

    Hematopoietic stem cells play the vital role of maintaining appropriate levels of cells in blood. Therefore, regulation of their fate is essential for their effective therapeutic use. Here we report the role of polyunsaturated fatty acids (PUFAs) in regulating hematopoiesis which has not been explored well so far. Mice were fed daily for 10 days with n-6/n-3 PUFAs, viz. linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid and docosahexanoic acid (DHA) in four separate test groups with phosphate-buffered saline fed mice as control set. The bone marrow cells of PUFA-fed mice showed a significantly higher hematopoiesis as assessed using side population, Lin-Sca-1 + ckit+, colony-forming unit (CFU), long-term culture, CFU-spleen assay and engraftment potential as compared to the control set. Thrombopoiesis was also stimulated in PUFA-fed mice. A combination of DHA and AA was found to be more effective than when either was fed individually. Higher incorporation of PUFAs as well as products of their metabolism was observed in the bone marrow cells of PUFA-fed mice. A stimulation of the Wnt, CXCR4 and Notch1 pathways was observed in PUFA-fed mice. The clinical relevance of this study was evident when bone marrow-transplanted recipient mice, which were fed with PUFAs, showed higher engraftment of donor cells, suggesting that the bone marrow microenvironment may also be stimulated by feeding with PUFAs. These data indicate that oral administration of PUFAs in mice stimulates hematopoiesis and thrombopoiesis and could serve as a valuable supplemental therapy in situations of hematopoietic failure. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Effects of irradiation on the production of factors regulating humoral hematopoiesis

    International Nuclear Information System (INIS)

    Seki, Masatoshi; Yoshida, Kazuko

    1974-01-01

    Changes in factors regulating humoral hematopoiesis after irradiation were studied by intraperitoneal insertion of cellulose acetate membrane (CA membrane). There is little possibility that regulation factors is produced by macrophage itself. The growth of the colony depends mainly on increase or decrease of regulation factors in the host. However, there is a possibility that the macrophage interferes the action of these regulation factors. From the fact that there is no action of EPO (erythropoiesis) in Sl/slsup(d) mice having abnormal function of microenvironment, it is suggested that the action of EPO is brought about through the function of the microenvironment. In the analysis of the colony formation by intraperitoneal insertion of CA membrane, it is considered that the erythroblastic colony can be formed by the macrophage through the action of EPO. In short, it is concluded that factors regulating humoral hematopoiesis increased in the body of the mouse which have been irradiated to the whole body, and the increase in these factors is not constant, but remarkably changes with time. (Namekawa, K.)

  11. Multi-particle phase space integration with arbitrary set of singularities in CompHEP

    International Nuclear Information System (INIS)

    Kovalenko, D.N.; Pukhov, A.E.

    1997-01-01

    We describe an algorithm of multi-particle phase space integration for collision and decay processes realized in CompHEP package version 3.2. In the framework of this algorithm it is possible to regularize an arbitrary set of singularities caused by virtual particle propagators. The algorithm is based on the method of the recursive representation of kinematics and on the multichannel Monte Carlo approach. CompHEP package is available by WWW: http://theory.npi.msu.su/pukhov/comphep. html (orig.)

  12. Cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis and its correlation with sonographic knee cartilage thickness and disease activity.

    Science.gov (United States)

    Sakthiswary, Rajalingham; Rajalingam, Shamala; Hussein, Heselynn; Sridharan, Radhika; Asrul, Abdul Wahab

    2017-12-01

    The aim of the study is to investigate the correlation of serum cartilage oligomeric matrix protein (COMP) levels with articular cartilage damage based on sonographic knee cartilage thickness (KCT) and disease activity in rheumatoid arthritis (RA). A total of 61 RA patients and 27 healthy controls were recruited in this study. Serum samples were obtained from all subjects to determine the serum COMP levels. All subjects had bilateral ultrasound scan of their knees. The KCT was based on the mean of measurements at three sites: the medial condyle, lateral condyle and intercondylar notch. Besides, the RA patients were assessed for their disease activity based on 28-joint-based Disease Activity Score (DAS 28). Serum COMP concentrations were significantly elevated in the RA patients compared to the controls (p = 0.001). The serum COMP levels had an inverse relationship with bilateral KCT in RA subjects and the healthy controls. COMP correlated significantly with disease activity based on DAS 28 (r = 0.299, p = 0.010), disease duration (r = 0.439, p = correlation between serum COMP and DAS 28 scores was comparable to the traditional markers of inflammation: erythrocyte sedimentation rate (ESR) (r = 0.372, p = 0.003) and C-reactive protein (CRP) (r = 0.305, p = 0.017). The serum COMP is a promising biomarker in RA which reflects disease activity and damage to the articular cartilage.

  13. Influência de estabilizantes na degradação foto-oxidativa de filmes de compósitos de SWy-1/poli(óxido de etileno

    Directory of Open Access Journals (Sweden)

    Patrícia Coelho Lombardo

    2015-02-01

    Full Text Available Compósitos de poli(óxido de etileno (PEO com argila montmorilonita SWy-1 e estabilizantes (2-hidroxibenzofenona e tinuvin 770 foram preparados pelo método de intercalação em solução. Os filmes obtidos foram expostos a irradiação UV, e os produtos da fotodegradação foram monitorados por FTIR (Fourier Transform Infrared Spectroscopy, ou Espectroscopia no infravermelho por transformada de Fourier e SEC (Size Exclusion Chromatography, ou cromatografia de exclusão por tamanho. O PEO puro apresentou maior coeficiente de degradação, kd, comparado com as demais amostras. O sistema que apresentou o menor valor para o coeficiente de degradação (kd = 1,9×10–6 mol g–1 h-1 foi o compósito de PEO/5%SWy-1 com 0,25% de tinuvin 770. Nesse caso, a estabilização da matriz de PEO pode ser atribuída à argila juntamente com o tinuvin 770. A argila dispersa e absorve a irradiação UV, e o tinuvin age como estabilizante do tipo HALS (do inglês hindered amine light stabilizer, ou estabilizantes à luz tipo aminas impedidas.

  14. A pulsão de morte e a gênese da angústia Death impulse and the genesis of anguish

    Directory of Open Access Journals (Sweden)

    Lara Cristina d'Avila Lourenço

    2009-06-01

    Full Text Available Com base na tese sobre a angústia somática, a qual assume que o substrato da angústia é a tensão sexual excessiva e desligada, apresenta-se a hipótese de que a ação da pulsão de morte sobre a pulsão de vida produz uma forma primordial de angústia. Essa angústia ainda não se caracterizaria como sensação, mas como pura quantidade que, com o desenvolvimento do aparelho psíquico, seria utilizada pelo ego para defesa. Portanto, a prontidão angustiada (Angstbereitschaft, descrita em Além do princípio do prazer, teria como fundamento tal forma de angústia.Based in the thesis about somatic anguish, which declares that the substratum of anguish are extreme sexual tension and extreme sexual off, this article presents the hypothesis that the action of death impulse around of life impulse produces a primordial form of anguish. This anguish is not yet characterized as sensation, but as pure amount that, with the development of the psychic apparatus, would be used by the ego for the defense. Therefore, the readiness for anguish (Angstbereitschaft, described in Beyond the principle of the pleasure, would have as bedding such form of anguish.

  15. Helical tomotherapy for extramedullary hematopoiesis involving the pericardium in a patient with chronic myeloid leukemia.

    Science.gov (United States)

    Toms, Daniel R; Cannick, Leander; Stuart, Robert K; Jenrette, Joseph M; Terwiliger, Lacy

    2010-07-01

    Extramedullary hematopoiesis (EMH) refers to the development of foci of hematopoiesis outside its normal location in the bone marrow. This occurs normally during fetal development but is abnormal postpartum. The most common sites of EMH are the spleen and liver. The phenomenon occurs in a number of disease states, notably in myelofibrosis, thalassemia, immune thrombocytopenic purpura, sickle cell anemia, polycythemia vera, and myelodysplastic syndrome. Affected patients often develop symptoms related to the location of the EMH. Reported treatments include red blood cell transfusions, surgical excision, decompressive laminectomy in cases of cord compression, chemotherapy, and irradiation. Radiation therapy is highly effective for treating hematopoietic tissue because such tissues are extremely radiosensitive. Megavoltage helical tomotherapy is a technical advance in the delivery of radiation therapy, allowing more conformal and precise treatments. The present case report describes a patient with the diagnosis of atypical chronic myeloid leukemia and myelofibrosis who subsequently developed EMH of the pericardium with effusion and tamponade. By utilizing tomotherapy we were able to treat the pericardium while sparing much of the myocardium. The patient tolerated treatment well without acute adverse effects. His symptoms were alleviated, but he died approximately 1 year later.

  16. Recover vigorous cells of Magnetospirillum magneticum AMB-1 by capillary magnetic separation

    Science.gov (United States)

    Li, Jinhua; Ge, Xin; Zhang, Xiaokui; Chen, Guanjun; Pan, Yongxin

    2010-07-01

    Cultivable magnetotactic bacteria (MTB) in laboratory can provide sufficient samples for molecular microbiological and magnetic studies. However, a cold-stored MTB strain, such as Magnetospirillum magneticum AMB-1, often loses its ability to synthesize magnetosomes and consequently fails to sense the external magnetic field. It is therefore important to quickly recover vigorous bacteria cells that highly capable of magnetosome producing. In this study, a modified capillary magnetic separation system was designed to recover a deteriorating strain of Magnetospirillum magneticum AMB-1 that long-term cold-stored in a refrigerator. The results show that all cells obtained after a 3-cycle treatment were vigorous and had the ability to produce magnetosomes. Moreover, the 3rd-cycle recovered cells were able to form more magnetosome crystals. Compared with the colony formation method, this new method is time-saving, easily operated, and more efficient for recovering vigorous MTB cells.

  17. A Rare Presentation of Extramedullary Hematopoiesis in Post-polycythemic Myelofibrosis

    OpenAIRE

    Konca Degertekin, Ceyla; Özkurt, Zübeyde Nur; Akyürek, Nalan; Yağcı, Münci

    2012-01-01

    Polycythemia vera is a clonal proliferative disorder of the bone marrow that could possibly evolve into myelofibrosis in its natural course. Progression to myelofibrosis is usually a late stage complication and presents clinically with refractory cytopenias and extramedullary hematopoiesis (EMH). EMH can occur in any tissue during the course of post-polycythemic myelofibrosis. However, skin and cardiac involvements seems to be very rare. We present a 56-year-old woman with post-polycythemic m...

  18. Compósitos polímero-madeira preparados por polimerização in situ de metil metacrilato usando aditivos bifuncionais

    Directory of Open Access Journals (Sweden)

    Bruno Dufau Mattos

    2015-12-01

    Full Text Available Resumo O presente trabalho teve por objetivo a confecção de compósitos polímero-madeira por meio de polimerização in situ de metil metacrilato (MMA, utilizando ácido metacrílico (MAA e glicidil metacrilato (GMA como agentes de ligação e reticulação. Amostras de madeira de guapuruvu foram impregnadas em um sistema de vácuo e pressão e polimerizadas em estufa a 90°C por 10h, usando 1,5% de peroxido de benzoíla como catalisador. Os compósitos foram caracterizados por meio de testes de absorção de água e estabilidade dimensional, molhabilidade, ATR-IR, TGA, MEV e WPG. Os espectros de ATR-IR mostraram incrementos nas bandas a 1746, 1460, e 1145 cm–1, referentes as estruturas químicas dos polímeros dentro da madeira, confirmado posteriormente pelas imagens de MEV. A termogravimetria apontou reações químicas entre os copolímeros e a parede celular da madeira nos compósitos com GMA e MAA. Os compósitos preparados com MMA apresentaram incrementos acima de 50% nas propriedades higroscópicas e de estabilidade dimensional, entretanto a adição de GMA e MAA resultou em maiores incrementos nas mesmas propriedades, entre 66-90%.

  19. Modelagem de dispositivo Iosipescu para medição de propriedades de cisalhamento de materiais compósitos

    OpenAIRE

    Fabrício Nascimento Ribeiro

    2013-01-01

    Os projetos de novas aeronaves possuem suas estruturas primárias fabricados em materiais compósitos, o que resulta em diferentes tipos de cargas agindo em peças de compósitos. O comportamento de compósitos sujeitos a carga de cisalhamento é algo difícil de caracterizar especialmente porque os ensaios de cisalhamento possuem dificuldades em obter uma condição de cisalhamento puro e uniforme. O presente trabalho busca modelar o ensaio de cisalhamento Iosipescu com o método de elementos finitos,...

  20. Angiotensin II reduces cardiac AdipoR1 expression through AT1 receptor/ROS/ERK1/2/c-Myc pathway.

    Directory of Open Access Journals (Sweden)

    Li Li

    Full Text Available Adiponectin, an abundant adipose tissue-derived protein, exerts protective effect against cardiovascular disease. Adiponectin receptors (AdipoR1 and AdipoR2 mediate the beneficial effects of adiponectin on the cardiovascular system. However, the alteration of AdipoRs in cardiac remodeling is not fully elucidated. Here, we investigated the effect of angiotensin II (AngII on cardiac AdipoRs expression and explored the possible molecular mechanism. AngII infusion into rats induced cardiac hypertrophy, reduced AdipoR1 but not AdipoR2 expression, and attenuated the phosphorylations of adenosine monophosphate-activated protein kinase and acetyl coenzyme A carboxylase, and those effects were all reversed by losartan, an AngII type 1 (AT1 receptor blocker. AngII reduced expression of AdipoR1 mRNA and protein in cultured neonatal rat cardiomyocytes, which was abolished by losartan, but not by PD123319, an AT2 receptor antagonist. The antioxidants including reactive oxygen species (ROS scavenger NAC, NADPH oxidase inhibitor apocynin, Nox2 inhibitor peptide gp91 ds-tat, and mitochondrial electron transport chain complex I inhibitor rotenone attenuated AngII-induced production of ROS and phosphorylation of extracellular signal-regulated kinase (ERK 1/2. AngII-reduced AdipoR1 expression was reversed by pretreatment with NAC, apocynin, gp91 ds-tat, rotenone, and an ERK1/2 inhibitor PD98059. Chromatin immunoprecipitation assay demonstrated that AngII provoked the recruitment of c-Myc onto the promoter region of AdipoR1, which was attenuated by PD98059. Moreover, AngII-induced DNA binding activity of c-Myc was inhibited by losartan, NAC, apocynin, gp91 ds-tat, rotenone, and PD98059. c-Myc small interfering RNA abolished the inhibitory effect of AngII on AdipoR1 expression. Our results suggest that AngII inhibits cardiac AdipoR1 expression in vivo and in vitro and AT1 receptor/ROS/ERK1/2/c-Myc pathway is required for the downregulation of AdipoR1 induced by AngII.

  1. Impaired Hematopoiesis and Disrupted Monocyte/Macrophage Homeostasis in Mucopolysaccharidosis Type I Mice.

    Science.gov (United States)

    Viana, Gustavo Monteiro; Buri, Marcus Vinícius; Paredes-Gamero, Edgar Julian; Martins, Ana Maria; D'Almeida, Vânia

    2016-03-01

    Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disease caused by alpha-L-iduronidase deficiency in which heparan and dermatan sulfate degradation is compromised. Besides primary lysosomal glycosaminoglycan accumulation, further changes in cellular functions have also been described in several murine MPS models. Herein, we evaluated alterations in hematopoiesis and its implications on the production of mature progeny in a MPS I murine model. Despite the significant increase in hematopoietic stem cells, a reduction in common myeloid progenitors and granulocyte-macrophage progenitor cells was observed in Idua -/- mice bone marrow. Furthermore, no alterations in number, viability nor activation of cell death mechanisms were observed in Idua -/- mice mature macrophages but they presented higher sensitivity to apoptotic induction after staurosporine treatment. In addition, changes in Ca(2+) signaling and a reduction in phagocytosis ability were also found. In summary, our results revealed significant intracellular changes in mature Idua -/- macrophages related to alterations in Idua -/- mice hematopoiesis, revealing a disruption in cell homeostasis. These results provide new insights into physiopathology of MPS I. © 2015 Wiley Periodicals, Inc.

  2. Superkondensatorių su anglies elektrodais, suformuotais iš elektrolankinio išlydžio argono-acetileno plamos, tyrimas

    OpenAIRE

    Kavaliauskas, Žydrūnas

    2010-01-01

    Disertacijoje nagrinėjama tematika yra susijusi su superkondensatorių formavimu ir jų tyrimais naudojant plazmines technologijas. Superkondensatorių elektrodams formuoti panaudota plazminio purškimo technologija. Anglis ant nerūdijančio plieno paviršiaus užnešta panaudojant atmosferinio slėgio argono-acetileno plazmą. Nikelio oksidui nusodinti ant anglies elektrodų paviršiaus panaudotas magnetroninio garinimo metodas. Įvertinta acetileno kiekio įtaka superkondensatorių elektrinėms charakteris...

  3. Activation of adenosine A3 receptors supports hematopoiesis-stimulating effects of granulocyte colony-stimulating factor in sublethally irradiated mice

    Czech Academy of Sciences Publication Activity Database

    Hofer, Michal; Pospíšil, Milan; Šefc, L.; Dušek, L.; Vacek, Antonín; Holá, Jiřina; Hoferová, Zuzana; Štreitová, Denisa

    2010-01-01

    Roč. 86, č. 8 (2010), s. 649-656 ISSN 0955-3002 R&D Projects: GA ČR(CZ) GA305/08/0158 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : ionising radiation * hematopoiesis * adenosine A3 receptors Subject RIV: BO - Biophysics Impact factor: 1.861, year: 2010

  4. Développer des compétences interactionnelles en collaborant à distance

    Directory of Open Access Journals (Sweden)

    Charlotte Dejean-Thircuir

    2010-01-01

    Full Text Available Cet article vise à montrer de quelles façons des étudiants d’un Master2 professionnel de didactique des langues engagés dans la réalisation d’une tâche collaborative à distance sont amenés à mettre en œuvre et à développer des compétences interactionnelles et des compétences instrumentales en construisant des schèmes d’utilisation de l’outil de communication qu’est le chat, dans ce contexte particulier. Cette étude s’inscrit dans le champ de la communication pédagogique médiatisée par ordinateur; l’analyse des interactions verbales entre étudiants s’appuie sur des outils issus du champ de la pragmatique linguistique interactionniste.

  5. Transjugular Intrahepatic Porto-Systemic Stent-Shunt for Therapy of Bleeding Esophageal Varices Due to Extramedullary Hematopoiesis in Primary Myelofibrosis: A Case Report

    OpenAIRE

    Phillip, Veit;Berger, Hermann;Straub, Melanie;Saugel, Bernd;Treiber, Matthias;Einwächter, Henrik;Schmid, Roland M.;Huber, Wolfgang

    2016-01-01

    Background: Primary myelofibrosis belongs to the group of myeloproliferative syndromes. Extramedullary hematopoiesis in the liver can lead to portal hypertension. Patient and Methods: We report a case of a patient with life-threatening, endoscopically not treatable bleeding from esophageal varices due to extramedullary hematopoiesis of the liver that was successfully treated with placement of a transjugular intrahepatic porto-systemic stent-shunt (TIPS). Results: Therapy of variceal bleeding ...

  6. Endothelial microparticle formation by angiotensin II is mediated via Ang II receptor type I/NADPH oxidase/ Rho kinase pathways targeted to lipid rafts.

    Science.gov (United States)

    Burger, Dylan; Montezano, Augusto C; Nishigaki, Nobuhiro; He, Ying; Carter, Anthony; Touyz, Rhian M

    2011-08-01

    Circulating microparticles are increased in cardiovascular disease and may themselves promote oxidative stress and inflammation. Molecular mechanisms underlying their formation and signaling are unclear. We investigated the role of reactive oxygen species (ROS), Rho kinase, and lipid rafts in microparticle formation and examined their functional significance in endothelial cells (ECs). Microparticle formation from angiotensin II (Ang II)-stimulated ECs and apolipoprotein E(-/-) mice was assessed by annexin V or by CD144 staining and electron microscopy. Ang II promoted microparticle formation and increased EC O(2)(-) generation and Rho kinase activity. Ang II-stimulated effects were inhibited by irbesartan (Ang II receptor type I blocker) and fasudil (Rho kinase inhibitor). Methyl-β-cyclodextrin and nystatin, which disrupt lipid rafts/caveolae, blocked microparticle release. Functional responses, assessed in microparticle-stimulated ECs, revealed increased O(2)(-) production, enhanced vascular cell adhesion molecule/platelet-EC adhesion molecule expression, and augmented macrophage adhesion. Inhibition of epidermal growth factor receptor blocked the prooxidative and proinflammatory effects of microparticles. In vitro observations were confirmed in apolipoprotein E(-/-) mice, which displayed vascular inflammation and high levels of circulating endothelial microparticles, effects that were reduced by apocynin. We demonstrated direct actions of Ang II on endothelial microparticle release, mediated through NADPH oxidase, ROS, and Rho kinase targeted to lipid rafts. Microparticles themselves stimulated endothelial ROS formation and inflammatory responses. Our findings suggest a feedforward system whereby Ang II promotes EC injury through its own endothelial-derived microparticles.

  7. The role of T2*-weighted gradient echo in the diagnosis of tumefactive intrahepatic extramedullary hematopoiesis in myelodysplastic syndrome and diffuse hepatic iron overload: a case report and review of the literature.

    Science.gov (United States)

    Belay, Abel A; Bellizzi, Andrew M; Stolpen, Alan H

    2018-01-15

    Extramedullary hematopoiesis is the proliferation of hematopoietic cells outside bone marrow secondary to marrow hematopoiesis failure. Extramedullary hematopoiesis rarely presents as a mass-forming hepatic lesion; in this case, imaging-based differentiation from primary and metastatic hepatic neoplasms is difficult, often leading to biopsy for definitive diagnosis. We report a case of tumefactive hepatic extramedullary hematopoiesis in the setting of myelodysplastic syndrome with concurrent hepatic iron overload, and the role of T2*-weighted gradient-echo magnetic resonance imaging in differentiating extramedullary hematopoiesis from primary and metastatic hepatic lesions. To the best of our knowledge, T2*-weighted gradient-echo evaluation of extramedullary hematopoiesis in the setting of diffuse hepatic hemochromatosis has not been previously described. A 52-year-old white man with myelodysplastic syndrome and marrow fibrosis was found to have a 4 cm hepatic lesion on ultrasound during workup for bone marrow transplantation. Magnetic resonance imaging revealed diffuse hepatic iron overload and non-visualization of the lesion on T2* gradient-echo sequence suggesting the presence of iron deposition within the lesion similar to that in background hepatic parenchyma. Subsequent ultrasound-guided biopsy of the lesion revealed extramedullary hematopoiesis. Six months later, while still being evaluated for bone marrow transplant, our patient was found to have poor pulmonary function tests. Follow-up computed tomography angiogram showed a mass within his right main pulmonary artery. Bronchoscopic biopsy of this mass once again revealed extramedullary hematopoiesis. He received radiation therapy to his chest. However, 2 weeks later, he developed mediastinal hematoma and died shortly afterward, secondary to respiratory arrest. Mass-forming extramedullary hematopoiesis is rare; however, our report emphasizes that it needs to be considered in the initial differential

  8. Angústia hipocondríaca e o eterno retorno do presente: considerações a partir do filme Sinédoque, New York

    OpenAIRE

    Klein, Thaís; Herzog, Regina

    2017-01-01

    Resumo A partir de questionamentos levantados pelo filme Sinédoque, New York (2008), pretende-se discutir a articulação da angústia hipocondríaca com a temporalidade. Observa-se que no filme o recurso do flashback não é utilizado; a temporalidade, que se instaura diante da angústia relacionada a sintomas hipocondríacos do personagem, calca-se em um presente absoluto. A hipocondria foi considerada por Freud uma neurose atual e a angústia a ela articulada opera como a contrapartida afetiva do e...

  9. Thalassemia, extramedullary hematopoiesis, and spinal cord compression: A case report.

    Science.gov (United States)

    Bukhari, Syed Sarmad; Junaid, Muhammad; Rashid, Mamoon Ur

    2016-01-01

    Extramedullary hematopoiesis (EMH) refers to hematopoiesis outside of the medulla of the bone. Chronic anemia states such as thalassemia can cause hematopoietic tissue to expand in certain locations. We report a case of spinal cord compression due to recurrent spinal epidural EMH, which was treated with a combination of surgery and radiotherapy. Pakistan has one of the highest incidence and prevalence of thalassemia in the world. We describe published literature on diagnosis and management of such cases. An 18-year-old male presented with bilateral lower limb paresis. He was a known case of homozygous beta thalassemia major. He had undergone surgery for spinal cord compression due to EMH 4 months prior to presentation. Symptom resolution was followed by deterioration 5 days later. He was operated again at our hospital with complete resection of the mass. He underwent local radiotherapy to prevent recurrence. At 2 years follow-up, he showed complete resolution of symptoms. Follow-up imaging demonstrated no residual mass. The possibility of EMH should be considered in every patient with ineffective erythropoiesis as a cause of spinal cord compression. Treatment of such cases is usually done with blood transfusions, which can reduce the hematopoietic drive for EMH. Other options include surgery, hydroxyurea, radiotherapy, or a combination of these on a case to case basis.

  10. Hematopoiesis-activating effects of androgen (fluoxymesterone)

    International Nuclear Information System (INIS)

    Shirakura, Takuo; Inoue, Tatsu; Maekawa, Tadashi.

    1978-01-01

    Hematopoiesis-activating effect of fluoxymesterone (FMT) (androgen preparation) on hematopoietic hematoblast was evaluated. The results were as follows. (1) To C 3 H/He strain male mice, 2 mg/day of FMT was injected into each femoral muscle alternatively. On the 5th day of the first injection, radioactive iron was injected intraperitoneally; after 48 hrs, blood was collected for examining the incorporation rate of 59 Fe. The results showed significant increase. (2) After 4 mg of FMT was injected once into the femoral muscle, spleen colony-forming cells (CFU-S) of the mouse femur were examined. Calculation of either of surface colonies and microscopic colonies showed absolute increase of the number of CFU-S in the femoral marrow. The microscopic colonies were classified into three colony types of erythrocytes, granulocytes, and megakaryocytes on the basis of histology of the cellular component; and changes were evaluated in each type of the colonies. This evaluation clarified that an increase in colonies which appeared 24 hrs after the injection of the hormon was due to an increase in the erythrocyte and megakaryocyte colonies and that which appeared 48 hrs after the injection was due to an increase in granulocyte colonies. (Ueda, J.)

  11. Compósitos a partir de materiais de fontes renováveis como alternativa para o desenvolvimento de produtos

    Directory of Open Access Journals (Sweden)

    Eliana Paula Calegari

    2016-04-01

    Full Text Available A preocupação ambiental tem gerado interesse na pesquisa de novos materiais que estejam alinhados com os princípios da sustentabilidade. Entre esses materiais, atualmente, encontram-se os compósitos produzidos a partir de recursos de fontes renováveis. Este artigo apresenta os resultados de um estudo de caso acerca de produtos em que são empregados os referidos compósitos. Realizou-se uma pesquisa na rede mundial de computadores usando a ferramenta de buscas google sobre produtos fabricados com esses compósitos e comparou-se com produtos fabricados a partir de materiais usualmente utilizados na indústria, tais como polímeros, metais e cerâmicas. Constatou-se que os compósitos feitos a partir de fontes renováveis estão sendo, principalmente, aplicados em embalagens, na produção de ferramentas para jardinagem e vasos para plantas. Dessa forma, observou-se que os referidos compósitos podem substituir materiais comumente empregados na indústria atendendo aos requisitos funcionais e estéticos demandados na confecção desses produtos.

  12. Compósitos de borracha natural com polianilina Composites of natural rubber with polyaniline

    Directory of Open Access Journals (Sweden)

    Patrini D. Galiani

    2007-06-01

    Full Text Available Compósitos de borracha natural (Hevea brasiliensis-BN/polianilina - PANI, com diferentes composições foram obtidos através da polimerização por emulsão do monômero anilina na presença da BN e do ácido dodecilbenzeno sulfônico (DBSA. Filmes finos e homogêneos foram obtidos por prensagem a quente. Os compósitos foram caracterizados por condutividade elétrica, FTIR, UV-vis-NIR, DSC e difração de raios X. Compósito com condutividade elétrica cerca de 14 ordens de grandeza maior que a BN foi obtido. Este alto valor de condutividade é atribuído à formação da PANI no estado dopado no compósito, que foi verificado através das técnicas de UV-vis-NIR e FTIR. Os resultados obtidos com a técnica de DSC e difratometria de raios X indicaram que os polímeros são imiscíveis e que a presença da borracha não altera significantemente a fase cristalina da PANI-DBSA no compósito.In this work composites with different compositions were obtained from natural rubber (Hevea brasiliensis (NR and polyaniline (PANI using the emulsion polymerization of aniline in the presence of NR and dodecylbenzenesulfonic acid (DBSA. The samples in film form were obtained by pressing the precipitate at 100 °C for 5 minutes. The composites were characterized by electrical conductivity, Fourier-transform infrared spectroscopy (FTIR, UV-vis-NIR spectroscopy, differential scanning calorimetry (DSC and X ray diffraction. Composites with electrical conductivity about 14 orders of magnitude higher than NR were obtained. The UV-vis-NIR and FTIR spectra showed that PANI-DBSA was formed in the composites, thus making it responsible for their high conductivity. The DSC thermograms indicated that the two polymers are immiscible and X ray diffraction evidenced that NB does not considerably affect PANI-DBSA crystalline phase in the composite.

  13. The effect of angiotensin 1-7 on tyrosine kinases activity in rat anterior pituitary

    International Nuclear Information System (INIS)

    Rebas, Elzbieta; Zabczynska, Joanna; Lachowicz, Agnieszka

    2006-01-01

    Angiotensin 1-7 (Ang 1-7) is a peptide originated from Ang II. It is known that in vessels Ang 1-7 shows opposite effects to Ang II. Ang 1-7 can modify processes of proliferation. However, Ang 1-7 action in pituitary gland cells was never studied. Moreover, the specific binding sites for Ang 1-7 are still unknown. The aim of this study was to examine the effects of Ang 1-7 on tyrosine kinases (PTKs) activity in the anterior pituitary. The reaction of phosphorylation was carrying out in presence of different concentration of Ang 1-7 and losartan (antagonist of AT1 receptor) and PD123319 (antagonist of AT2). Our results show that Ang 1-7 inhibited activity of PTK to 60% of basic activity. Losartan did not change the Ang 1-7-induced changes in PTKs activity. The presence of PD123319 together with Ang 1-7 caused stronger inhibition PTKs activity than Ang 1-7 alone. These observations suggest that Ang 1-7 binds to the novel, unknown, specific for this peptide receptor

  14. Êtres capables et compétents : lecture anthropologique et pistes pragmatiques

    OpenAIRE

    Genard, Jean-Louis; Cantelli, Fabrizio

    2008-01-01

    Les termes « compétences » et « capacités » occupent depuis quelques années une place de plus en plus importante dans le vocabulaire de la sociologie, notamment de la sociologie pragmatique. On les retrouve toutefois aussi dans d’autres champs théoriques (le terme capabilities chez Amartya Sen) ou dans le vocabulaire des politiques publiques qui évoquent des politiques de « capacitation », ou des « seuils de compétences ». Face à ce constat, l’article développe l’hypothèse d’un véritable tour...

  15. The semantics of Chemical Markup Language (CML for computational chemistry : CompChem

    Directory of Open Access Journals (Sweden)

    Phadungsukanan Weerapong

    2012-08-01

    Full Text Available Abstract This paper introduces a subdomain chemistry format for storing computational chemistry data called CompChem. It has been developed based on the design, concepts and methodologies of Chemical Markup Language (CML by adding computational chemistry semantics on top of the CML Schema. The format allows a wide range of ab initio quantum chemistry calculations of individual molecules to be stored. These calculations include, for example, single point energy calculation, molecular geometry optimization, and vibrational frequency analysis. The paper also describes the supporting infrastructure, such as processing software, dictionaries, validation tools and database repositories. In addition, some of the challenges and difficulties in developing common computational chemistry dictionaries are discussed. The uses of CompChem are illustrated by two practical applications.

  16. On-line process analysis innovation: DiComp (tm) shunting dielectric sensor technology

    Science.gov (United States)

    Davis, Craig R.; Waldman, Frank A.

    1993-01-01

    The DiComp Shunting Dielectric Sensor (SDS) is a new patent-pending technology developed under the Small Business Innovation Research Program (SBIR) for NASA's Kennedy Space Center. The incorporation of a shunt electrode into a conventional fringing field dielectric sensor makes the SDS uniquely sensitive to changes in material dielectric properties in the KHz to MHz range which were previously detectable only at GHz measurement frequencies. The initial NASA application of the SDS for Nutrient Delivery Control has demonstrated SDS capabilities for thickness and concentration measurement of Hoagland nutrient solutions. The commercial introduction of DiComp SDS technology for concentration and percent solids measurements in dispersions, emulsions and solutions represents a new technology for process measurements for liquids in a variety of industries.

  17. The semantics of Chemical Markup Language (CML) for computational chemistry : CompChem.

    Science.gov (United States)

    Phadungsukanan, Weerapong; Kraft, Markus; Townsend, Joe A; Murray-Rust, Peter

    2012-08-07

    : This paper introduces a subdomain chemistry format for storing computational chemistry data called CompChem. It has been developed based on the design, concepts and methodologies of Chemical Markup Language (CML) by adding computational chemistry semantics on top of the CML Schema. The format allows a wide range of ab initio quantum chemistry calculations of individual molecules to be stored. These calculations include, for example, single point energy calculation, molecular geometry optimization, and vibrational frequency analysis. The paper also describes the supporting infrastructure, such as processing software, dictionaries, validation tools and database repositories. In addition, some of the challenges and difficulties in developing common computational chemistry dictionaries are discussed. The uses of CompChem are illustrated by two practical applications.

  18. Improved of Natural Gas Storage with Adsorbed Natural Gas (ANG) Technology Using Activated Carbon from Plastic Waste Polyethylene Terepthalate

    Science.gov (United States)

    Yuliusman; Nasruddin; Sanal, A.; Bernama, A.; Haris, F.; Hardhi, M.

    2017-07-01

    Indonesia imports high amount of Fuel Oil. Although Indonesia has abundant amount of natural gas reserve, the obstacle lies within the process of natural gas storage itself. In order to create a safe repository, the ANG (Adsorbed Natural Gas) technology is planned. ANG technology in itself has been researched much to manufacture PET-based activated carbon for natural gas storage, but ANG still has several drawbacks. This study begins with making preparations for the equipment and materials that will be used, by characterizing the natural gas, measuring the empty volume, and degassing. The next step will be to examine the adsorption process. The maximum storage capacity obtained in this study for a temperature of 27°C and pressure of 35 bar is 0.0586 kg/kg, while for the desorption process, a maximum value for desorption efficiency was obtained on 35°C temperature with a value of 73.39%.

  19. Transjugular intrahepatic porto-systemic stent-shunt for therapy of bleeding esophageal varices due to extramedullary hematopoiesis in primary myelofibrosis: a case report.

    Science.gov (United States)

    Phillip, Veit; Berger, Hermann; Straub, Melanie; Saugel, Bernd; Treiber, Matthias; Einwächter, Henrik; Schmid, Roland M; Huber, Wolfgang

    2012-01-01

    Primary myelofibrosis belongs to the group of myeloproliferative syndromes. Extramedullary hematopoiesis in the liver can lead to portal hypertension. We report a case of a patient with life-threatening, endoscopically not treatable bleeding from esophageal varices due to extramedullary hematopoiesis of the liver that was successfully treated with placement of a transjugular intrahepatic porto-systemic stent-shunt (TIPS). Therapy of variceal bleeding by TIPS insertion was successful. During a 29-month follow-up, no hepatic failure, hepatic encephalopathy, or further variceal bleeding episode occurred. TIPS placement is a well-established procedure for the treatment of complications due to portal hypertension mainly due to liver cirrhosis. This report illustrates that TIPS placement can also be a promising treatment option in patients with primary myelofibrosis and portal hypertension due to extramedullary hematopoiesis. Copyright © 2012 S. Karger AG, Basel.

  20. Insect immunology and hematopoiesis.

    Science.gov (United States)

    Hillyer, Julián F

    2016-05-01

    Insects combat infection by mounting powerful immune responses that are mediated by hemocytes, the fat body, the midgut, the salivary glands and other tissues. Foreign organisms that have entered the body of an insect are recognized by the immune system when pathogen-associated molecular patterns bind host-derived pattern recognition receptors. This, in turn, activates immune signaling pathways that amplify the immune response, induce the production of factors with antimicrobial activity, and activate effector pathways. Among the immune signaling pathways are the Toll, Imd, Jak/Stat, JNK, and insulin pathways. Activation of these and other pathways leads to pathogen killing via phagocytosis, melanization, cellular encapsulation, nodulation, lysis, RNAi-mediated virus destruction, autophagy and apoptosis. This review details these and other aspects of immunity in insects, and discusses how the immune and circulatory systems have co-adapted to combat infection, how hemocyte replication and differentiation takes place (hematopoiesis), how an infection prepares an insect for a subsequent infection (immune priming), how environmental factors such as temperature and the age of the insect impact the immune response, and how social immunity protects entire groups. Finally, this review highlights some underexplored areas in the field of insect immunobiology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Estudo do comportamento da resina base na formulação de compósitos de politetrafluoretileno com bronze

    OpenAIRE

    Ronaldo Euzébio Bento

    2011-01-01

    Resumo: Esse trabalho concentra os estudos na investigação das propriedades de resistência a tração e alongamento do compósito de Politetrafluoretileno (PTFE) com 60% de bronze após a substituição do tipo de PTFE utilizado na formulação desse compósito. Atualmente esse compósito utiliza PTFE convencional na formulação e o objetivo é alterar para PTFE modificado. A motivação para essa alteração deveu-se ao fato que o PTFE convencional apresenta disponibilidade limitada dificultando o desenvolv...

  2. CompTIA Linux+ study guide exam LX0-103 and exam LX0-104

    CERN Document Server

    Bresnahan, Christine

    2015-01-01

    CompTIA Authorized Linux+ prepCompTIA Linux+ Study Guide is your comprehensive study guide for the Linux+ Powered by LPI certification exams. With complete coverage of 100% of the objectives on both exam LX0-103 and exam LX0-104, this study guide provides clear, concise information on all aspects of Linux administration, with a focus on the latest version of the exam. You'll gain the insight of examples drawn from real-world scenarios, with detailed guidance and authoritative coverage of key topics, including GNU and Unix commands, system operation, system administration, system services, secu

  3. CompTIA Linux+ Complete Study Guide (Exams LX0-101 and LX0-102)

    CERN Document Server

    Smith, Roderick W

    2010-01-01

    Prepare for CompTIA's Linux+ Exams. As the Linux server and desktop markets continue to grow, so does the need for qualified Linux administrators. CompTIA's Linux+ certification (Exams LX0-101 and LX0-102) includes the very latest enhancements to the popular open source operating system. This detailed guide not only covers all key exam topics—such as using Linux command-line tools, understanding the boot process and scripts, managing files and file systems, managing system security, and much more—it also builds your practical Linux skills with real-world examples. Inside, you'll find:. Full co

  4. Clonal hematopoiesis in acquired aplastic anemia.

    Science.gov (United States)

    Ogawa, Seishi

    2016-07-21

    Clonal hematopoiesis (CH) in aplastic anemia (AA) has been closely linked to the evolution of late clonal disorders, including paroxysmal nocturnal hemoglobinuria and myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML), which are common complications after successful immunosuppressive therapy (IST). With the advent of high-throughput sequencing of recent years, the molecular aspect of CH in AA has been clarified by comprehensive detection of somatic mutations that drive clonal evolution. Genetic abnormalities are found in ∼50% of patients with AA and, except for PIGA mutations and copy-neutral loss-of-heterozygosity, or uniparental disomy (UPD) in 6p (6pUPD), are most frequently represented by mutations involving genes commonly mutated in myeloid malignancies, including DNMT3A, ASXL1, and BCOR/BCORL1 Mutations exhibit distinct chronological profiles and clinical impacts. BCOR/BCORL1 and PIGA mutations tend to disappear or show stable clone size and predict a better response to IST and a significantly better clinical outcome compared with mutations in DNMT3A, ASXL1, and other genes, which are likely to increase their clone size, are associated with a faster progression to MDS/AML, and predict an unfavorable survival. High frequency of 6pUPD and overrepresentation of PIGA and BCOR/BCORL1 mutations are unique to AA, suggesting the role of autoimmunity in clonal selection. By contrast, DNMT3A and ASXL1 mutations, also commonly seen in CH in the general population, indicate a close link to CH in the aged bone marrow, in terms of the mechanism for selection. Detection and close monitoring of somatic mutations/evolution may help with prediction and diagnosis of clonal evolution of MDS/AML and better management of patients with AA. © 2016 by The American Society of Hematology.

  5. Emprego experimental da placa de compósito poli-hidroxibutirado/hidroxiapatita na fixação femoral em gatos

    Directory of Open Access Journals (Sweden)

    E.G.L. Alves

    2010-10-01

    Full Text Available Avaliou-se o compósito de poli-hidroxibutirado (PHB 70% e hidroxiapatita (HA 30% na forma de placas para fixação óssea em gatos. Foram usadas placas do compósito com 60mm de comprimento por 10mm de largura e espessura variando de 3mm no centro a 5mm nas extremidades, com seis orifícios. A placa do compósito foi empregada na fixação de osteotomia de fêmur em quatro gatos, totalizando seis intervenções. Verificou-se a ruptura de cinco placas (83,3% até o quarto dia e de uma placa (16,7% aos 21 dias, quando se observou um calo ósseo exuberante. O resultado da implantação da placa no gato mostrou que o compósito não possui resistência suficiente para ser empregado como placas de fixação de fêmur em gatos.

  6. Hematopoiesis on cellulose ester membranes (CEM). X. Effects of in vitro irradiation of stromal cells prior to application on CEM

    International Nuclear Information System (INIS)

    Knospe, W.H.; Husseini, S.G.

    1986-01-01

    Cellulose ester membranes (CEM) were coated with stromal cells from murine bone or bone marrow irradiated in vitro with 1000, 2000, or 4000 rad and then implanted i.p. in CAF1 mice for periods of six and 12 months. CEM coated with stromal cells from bone showed excellent regeneration of bone and hematopoiesis after 1000 rad in vitro irradiation. After 2000 rad, hematopoietic and bone regeneration was reduced by about 50%, and after 4000 rad it was completely absent in CEM coated with stromal cells from bone. CEM coated with stromal cells from bone marrow showed no regeneration of hematopoiesis or bone after 1000, 2000, and 4000 rad in vitro irradiation and residence i.p. for six and 12 months. These results indicate that regeneration of the hematopoietic microenvironment is dependent upon living stromal cells. A difference in radiation sensitivity is demonstrated between stromal cells from bone and from bone marrow

  7. Teaching Competencies for the Online Environment | Enseigner les compétences pour l’environnement en ligne

    Directory of Open Access Journals (Sweden)

    Heather Marie Farmer

    2016-08-01

    Full Text Available The goals of this study are to identify key competency areas that lead to success in online instruction and to develop a framework that supports professional development and self-assessment. To identify the key competency areas, skills and behaviours presented within current literature were analyzed. Secondly, gaps were identified and levels of competence were determined within each key competency area. The resulting analysis produced the Online Teaching Competency (OTC Matrix including five competency areas: Community & Netiquette, Active Teaching/Facilitating, Instructional Design, Tools & Technology, and Leadership & Instruction. This leveled competency matrix can be used to inform professional development in the online teaching environment and is also a useful guide in the areas of self-assessment, portfolio design, and the development and evaluation of professional development opportunities. Cette étude a comme objectifs de cerner les principaux domaines de compétences qui mènent à la réussite de l’instruction en ligne et de développer un cadre qui soutient le développement professionnel et l’autoévaluation. Afin de cerner les principaux domaines de compétences, une analyse des aptitudes et comportements présentés dans les études actuelles a été réalisée. Deuxièmement, les écueils ont été cernés et les niveaux de compétence ont été déterminés au sein de chaque domaine de compétences. L’analyse qui en a résulté a généré la matrice des compétences de l’enseignement en ligne, comprenant cinq domaines de compétences : collectivité et nétiquette, enseignement actif/animation active, conception de l’instruction, outils et technologie, ainsi que leadership et instruction. Cette matrice graduée peut servir à façonner le développement professionnel dans un environnement d’enseignement en ligne. Elle sert aussi de guide pratique pour les domaines de l’auto-évaluation, de la conception de

  8. Post-spinal cord injury astrocyte-mediated functional recovery in rats after intraspinal injection of the recombinant adenoviral vectors Ad5-VEGF and Ad5-ANG.

    Science.gov (United States)

    Povysheva, Tatyana; Shmarov, Maksim; Logunov, Denis; Naroditsky, Boris; Shulman, Ilya; Ogurcov, Sergey; Kolesnikov, Pavel; Islamov, Rustem; Chelyshev, Yuri

    2017-07-01

    directions from the points of injection. A 1.5 to 2.0-fold increase in the number of GFAP + , S100β + , and AQP4 + cells was observed in the white and gray matter at a distance of up to 5 mm from the center of the lesion site in the caudal and rostral directions. At 30 days after injury, a 2-fold increase in S100β transcripts was observed in the Ad5-VEGF+Ad5-ANG group compared with the control group. CONCLUSIONS Intraspinal injection of recombinant adenoviral vectors encoding VEGF and ANG stimulates functional recovery after traumatic SCI. The increased number of S100β + astrocytes induced by this approach may be a beneficial factor for maintaining the survival and function of neurons. Therefore, gene therapy with Ad5-VEGF+Ad5-ANG vectors is an effective therapeutic method for SCI treatment.

  9. Mild myopathy is associated with COMP but not MATN3 mutations in mouse models of genetic skeletal diseases.

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    Katarzyna A Piróg

    Full Text Available Pseudoachondroplasia (PSACH and multiple epiphyseal dysplasia (MED are skeletal disorders resulting from mutations in COMP, matrilin-3 or collagen IX and are characterised by short-limbed dwarfism and premature osteoarthritis. Interestingly, recent reports suggest patients can also manifest with muscle weakness. Here we present a detailed analysis of two mouse models of the PSACH/MED disease spectrum; ΔD469 T3-COMP (PSACH and V194D matrilin-3 (MED. In grip test experiments T3-COMP mice were weaker than wild-type littermates, whereas V194D mice behaved as controls, confirming that short-limbed dwarfism alone does not contribute to PSACH/MED-related muscle weakness. Muscles from T3-COMP mice showed an increase in centronuclear fibers at the myotendinous junction. T3-COMP tendons became more lax in cyclic testing and showed thicker collagen fibers when compared with wild-type tissue; matrilin-3 mutant tissues were indistinguishable from controls. This comprehensive study of the myopathy associated with PSACH/MED mutations enables a better understanding of the disease progression, confirms that it is genotype specific and that the limb weakness originates from muscle and tendon pathology rather than short-limbed dwarfism itself. Since some patients are primarily diagnosed with neuromuscular symptoms, this study will facilitate better awareness of the differential diagnoses that might be associated with the PSACH/MED spectrum and subsequent care of PSACH/MED patients.

  10. Myelopathy due to Spinal Extramedullary Hematopoiesis in a Patient with Polycythemia Vera

    Directory of Open Access Journals (Sweden)

    Shuhei Ito

    2017-01-01

    Full Text Available Extramedullary hematopoiesis (EMH occasionally occurs in patients exhibiting hematological disorders with decreased hematopoietic efficacy. EMH is rarely observed in the spinal epidural space and patients are usually asymptomatic. In particular, in the patients with polycythemia vera, spinal cord compression due to EMH is extremely rare. We report a case of polycythemia vera, in which operative therapy proved to be an effective treatment for myelopathy caused by spinal EMH.

  11. Myelopathy due to Spinal Extramedullary Hematopoiesis in a Patient with Polycythemia Vera.

    Science.gov (United States)

    Ito, Shuhei; Fujita, Nobuyuki; Hosogane, Naobumi; Nagoshi, Narihito; Yagi, Mitsuru; Iwanami, Akio; Watanabe, Kota; Tsuji, Takashi; Nakamura, Masaya; Matsumoto, Morio; Ishii, Ken

    2017-01-01

    Extramedullary hematopoiesis (EMH) occasionally occurs in patients exhibiting hematological disorders with decreased hematopoietic efficacy. EMH is rarely observed in the spinal epidural space and patients are usually asymptomatic. In particular, in the patients with polycythemia vera, spinal cord compression due to EMH is extremely rare. We report a case of polycythemia vera, in which operative therapy proved to be an effective treatment for myelopathy caused by spinal EMH.

  12. Myelopathy due to Spinal Extramedullary Hematopoiesis in a Patient with Polycythemia Vera

    OpenAIRE

    Ito, Shuhei; Fujita, Nobuyuki; Hosogane, Naobumi; Nagoshi, Narihito; Yagi, Mitsuru; Iwanami, Akio; Watanabe, Kota; Tsuji, Takashi; Nakamura, Masaya; Matsumoto, Morio; Ishii, Ken

    2017-01-01

    Extramedullary hematopoiesis (EMH) occasionally occurs in patients exhibiting hematological disorders with decreased hematopoietic efficacy. EMH is rarely observed in the spinal epidural space and patients are usually asymptomatic. In particular, in the patients with polycythemia vera, spinal cord compression due to EMH is extremely rare. We report a case of polycythemia vera, in which operative therapy proved to be an effective treatment for myelopathy caused by spinal EMH.

  13. Temporal bone extramedullary hematopoiesis as a causeof pediatric bilateral conductive hearing loss:Case report and review of the literature.

    Science.gov (United States)

    Lanigan, Alexander; Fordham, M Taylor

    2017-06-01

    Extramedullary hematopoiesis occurs in children with hemoglobinopathy and chronic anemia. The liver and spleen are often affected first, but other foci can develop to support erythrocyte demand. We report a case of a nine-year-old with beta thalassemia and temporal bone extramedullary hematopoiesis causing ossicular fixation and bilateral conductive hearing loss. There is only one case in the literature describing this phenomenon in pediatric patients, and this is the first case report of bilateral hearing loss from this physiologic phenomenon. Otolaryngologists should consider this etiology in patients with chronic anemia and conductive hearing loss in the absence of otitis media. Published by Elsevier B.V.

  14. Dysregulation of angiopoietins is associated with placental malaria and low birth weight.

    Directory of Open Access Journals (Sweden)

    Karlee L Silver

    Full Text Available BACKGROUND: Placental malaria (PM is associated with adverse pregnancy outcomes including low birth weight (LBW. However, the precise mechanisms by which PM induces LBW are poorly defined. Based on the essential role of angiopoietin (ANG-1 and -2 in normal placental vascular development, we hypothesized that PM may result in the dysregulation of angiopoietins and thereby contribute to LBW outcomes. METHODS AND FINDINGS: In a mouse model of PM, we show that Plasmodium berghei ANKA infection of pregnant mice resulted in dysregulated angiopoietin levels and fetal growth restriction. PM lead to decreased ANG-1, increased ANG-2, and an elevated ratio of ANG-2/ANG-1 in the placenta and the serum. These observations were extended to malaria-exposed pregnant women: In a study of primigravid women prospectively followed over the course of pregnancy, Plasmodium falciparum infection was associated with a decrease in maternal plasma ANG-1 levels (P = 0.031 and an increase in the ANG-2:ANG-1 ratio (P = 0.048. ANG-1 levels recovered with successful treatment of peripheral parasitemia (P = 0.010. In a cross-sectional study of primigravidae at delivery, angiopoietin dysregulation was associated with PM (P = 0.002 and LBW (P = 0.041. Women with PM who delivered LBW infants had increased ANG-2:ANG-1 ratios (P = 0.002 compared to uninfected women delivering normal birth weight infants. CONCLUSIONS: These data support the hypothesis that dysregulation of angiopoietins is associated with PM and LBW outcomes, and suggest that ANG-1 and ANG-2 levels may be clinically informative biomarkers to identify P. falciparum-infected mothers at risk of LBW deliveries.

  15. Adrenal extramedullary hematopoiesis associated with β-thalassemia major.

    Science.gov (United States)

    Keikhaei, Bijan; Shirazi, Ahmad Soltani; Pour, Mahboob Mohammad

    2012-05-10

    The presence of apparently normal hematopoietic tissue outside of bone marrow cavity is defined as extramedullary hematopoiesis (EMH). EMH is a rare complication in thalassemia major (TM) and adrenal gland as well. This report describes a case of adrenal EMH in a 26-year-old man with β-TM. He has been transfused with regular blood transfusion since 9 months. During the routine physical examination he was incidentally found to have a hypoechoic mass at his abdominal ultrasonography. Abdominal computed tomography scan revealed a right well-defined suprarenal mass 7.7×7.3×5.8 cm in size. The diagnosis of EMH was confirmed with ultrasonographic-guided fine needle biopsy. Treatment options which include intensified regular blood transfusion and hydroxyurea have been started.

  16. Normal hematopoiesis and lack of β-catenin activation in osteoblasts of patients and mice harboring Lrp5 gain of function mutations

    DEFF Research Database (Denmark)

    Galan-Diez, Marta; Isa, Adiba; Ponzetti, Marco

    2016-01-01

    of hematopoiesis and leukemogenic properties of β-catenin activation in osteoblasts, that lead to development of acute myeloid leukemia (AML). Using mice with gain-of-function (GOF) Lrp5 alleles (Lrp5(A214V)) that recapitulate the human high bone mass (HBM) phenotype, as well as patients with the T253I HBM Lrp5...... mutation, we show here that Lrp5 GOF mutations in both humans and mice do not activate β-catenin signaling in osteoblasts. Consistent with a lack of β-catenin activation in their osteoblasts, Lrp5(A214V) mice have normal trilinear hematopoiesis. In contrast to leukemic mice with constitutive activation...... of β-catenin in osteoblasts (Ctnnb1(CAosb)), accumulation of early myeloid progenitors, a characteristic of AML, myeloid-blasts in blood, and segmented neutrophils or dysplastic megakaryocytes in the bone marrow, are not observed in Lrp5(A214V) mice. Likewise, peripheral blood count analysis in HBM...

  17. Chymase-dependent generation of angiotensin II from angiotensin-(1-12 in human atrial tissue.

    Directory of Open Access Journals (Sweden)

    Sarfaraz Ahmad

    Full Text Available Since angiotensin-(1-12 [Ang-(1-12] is a non-renin dependent alternate precursor for the generation of cardiac Ang peptides in rat tissue, we investigated the metabolism of Ang-(1-12 by plasma membranes (PM isolated from human atrial appendage tissue from nine patients undergoing cardiac surgery for primary control of atrial fibrillation (MAZE surgical procedure. PM was incubated with highly purified ¹²⁵I-Ang-(1-12 at 37°C for 1 h with or without renin-angiotensin system (RAS inhibitors [lisinopril for angiotensin converting enzyme (ACE, SCH39370 for neprilysin (NEP, MLN-4760 for ACE2 and chymostatin for chymase; 50 µM each]. ¹²⁵I-Ang peptide fractions were identified by HPLC coupled to an inline γ-detector. In the absence of all RAS inhibitor, ¹²⁵I-Ang-(1-12 was converted into Ang I (2±2%, Ang II (69±21%, Ang-(1-7 (5±2%, and Ang-(1-4 (2±1%. In the absence of all RAS inhibitor, only 22±10% of ¹²⁵I-Ang-(1-12 was unmetabolized, whereas, in the presence of the all RAS inhibitors, 98±7% of ¹²⁵I-Ang-(1-12 remained intact. The relative contribution of selective inhibition of ACE and chymase enzyme showed that ¹²⁵I-Ang-(1-12 was primarily converted into Ang II (65±18% by chymase while its hydrolysis into Ang II by ACE was significantly lower or undetectable. The activity of individual enzyme was calculated based on the amount of Ang II formation. These results showed very high chymase-mediated Ang II formation (28±3.1 fmol × min⁻¹ × mg⁻¹, n = 9 from ¹²⁵I-Ang-(1-12 and very low or undetectable Ang II formation by ACE (1.1±0.2 fmol×min⁻¹ × mg⁻¹. Paralleling these findings, these tissues showed significant content of chymase protein that by immunocytochemistry were primarily localized in atrial cardiac myocytes. In conclusion, we demonstrate for the first time in human cardiac tissue a dominant role of cardiac chymase in the formation of Ang II from Ang-(1-12.

  18. Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Libregts, Sten F.W.M.; Nolte, Martijn A., E-mail: m.nolte@sanquin.nl

    2014-12-10

    Quiescence, self-renewal, lineage commitment and differentiation of hematopoietic stem cells (HSCs) towards fully mature blood cells are a complex process that involves both intrinsic and extrinsic signals. During steady-state conditions, most hematopoietic signals are provided by various resident cells inside the bone marrow (BM), which establish the HSC micro-environment. However, upon infection, the hematopoietic process is also affected by pathogens and activated immune cells, which illustrates an effective feedback mechanism to hematopoietic stem and progenitor cells (HSPCs) via immune-mediated signals. Here, we review the impact of pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), costimulatory molecules and pro-inflammatory cytokines on the quiescence, proliferation and differentiation of HSCs and more committed progenitors. As modulation of HSPC function via these immune-mediated signals holds an interesting parallel with the “three-signal-model” described for the activation and differentiation of naïve T-cells, we propose a novel “three-signal” concept for immune-driven hematopoiesis. In this model, the recognition of PAMPs and DAMPs will activate HSCs and induce proliferation, while costimulatory molecules and pro-inflammatory cytokines confer a second and third signal, respectively, which further regulate expansion, lineage commitment and differentiation of HSPCs. We review the impact of inflammatory stress on hematopoiesis along these three signals and we discuss whether they act independently from each other or that concurrence of these signals is important for an adequate response of HSPCs upon infection. - Highlights: • Inflammation and infection have a direct impact on hematopoiesis in the bone marrow. • We draw a striking parallel between immune-driven hematopoiesis and T cell activation. • We review how PAMPs and DAMPs, costimulation and cytokines influence HSPC function.

  19. Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow

    International Nuclear Information System (INIS)

    Libregts, Sten F.W.M.; Nolte, Martijn A.

    2014-01-01

    Quiescence, self-renewal, lineage commitment and differentiation of hematopoietic stem cells (HSCs) towards fully mature blood cells are a complex process that involves both intrinsic and extrinsic signals. During steady-state conditions, most hematopoietic signals are provided by various resident cells inside the bone marrow (BM), which establish the HSC micro-environment. However, upon infection, the hematopoietic process is also affected by pathogens and activated immune cells, which illustrates an effective feedback mechanism to hematopoietic stem and progenitor cells (HSPCs) via immune-mediated signals. Here, we review the impact of pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), costimulatory molecules and pro-inflammatory cytokines on the quiescence, proliferation and differentiation of HSCs and more committed progenitors. As modulation of HSPC function via these immune-mediated signals holds an interesting parallel with the “three-signal-model” described for the activation and differentiation of naïve T-cells, we propose a novel “three-signal” concept for immune-driven hematopoiesis. In this model, the recognition of PAMPs and DAMPs will activate HSCs and induce proliferation, while costimulatory molecules and pro-inflammatory cytokines confer a second and third signal, respectively, which further regulate expansion, lineage commitment and differentiation of HSPCs. We review the impact of inflammatory stress on hematopoiesis along these three signals and we discuss whether they act independently from each other or that concurrence of these signals is important for an adequate response of HSPCs upon infection. - Highlights: • Inflammation and infection have a direct impact on hematopoiesis in the bone marrow. • We draw a striking parallel between immune-driven hematopoiesis and T cell activation. • We review how PAMPs and DAMPs, costimulation and cytokines influence HSPC function

  20. Modelos de percolação elétrica aplicados para compósitos poliméricos condutores

    Directory of Open Access Journals (Sweden)

    Paulo Henrique da Silva Leite Coelho

    Full Text Available Resumo O presente artigo apresenta a aplicação e adequação dos modelos de percolação elétrica em trabalhos experimentais e teóricos da literatura para compósitos poliméricos condutores. Foi realizado um levantamento das publicações referentes aos modelos estudados para os diferentes tipos de cargas condutoras mais aplicadas na preparação destes compósitos, tais como pós metálicos, grafite, negro de fumo, nanofibras e nanotubos de carbono. A discussão está apresentada quanto à adequação dos modelos ao comportamento dos compósitos na influência das cargas nas propriedades elétricas de matrizes poliméricas.

  1. Equivalent flow rate concept used in near field transport model COMP23 - Proposed values for SR 97

    International Nuclear Information System (INIS)

    Moreno, L.

    1998-11-01

    SKB is using NUCTRAN to calculate transport of radionuclides from a possible defective canister into the far field. NUCTRAN is included in the Performance Assessment model chain that calculates the release from the canister into the biosphere. In the chain, NUCTRAN is denoted COMP23. In order to calculate the transport of radionuclides by diffusion into the flowing water in the rock, NUCTRAN uses the concept of equivalent flow rate, Q eq . To calculate the value of Q eq in the different paths, COMP23 needs information about the Darcy velocity, the geometry of the system, material properties and the flow porosity in the rock. At present, this information is supplied to COMP23 by means of three parameters. The aim of this note is to propose a method to calculate the flow equivalent within the SR 97 project. Estimated intervals of the factors to adopt HYDRASTAR results to COMP23 are presented. Since it is difficult to give general validity to the factors, solely proposed factor intervals are presented to obtain equivalent flow rate values for COMP23. To obtain accurate equivalent flow rate values, information about the hydraulic conditions at canister locations in the groundwater model should be available for the near field model or the Q eq values could be calculated directly in the groundwater flow model. One of the main tasks in the SR 97 project is to show the barrier performance of the rock using different alternative models for flow and transport. In addition, the Alternative Model Project (AMP) aims to show how robust the assessment model description is, in terms of relevant far field performance measures. In the AMP, three main approaches were used, namely, the Stochastic Continuum approach, the Channel Network model and the Discrete Feature Network model

  2. Vinte Poemas de Amor - Uma leitura da angústia na perspectiva freudiana

    Directory of Open Access Journals (Sweden)

    Vanessa Aparecida Alves Lima

    2015-07-01

    Full Text Available Este é o momento do encontro de uma parte da teoria freudiana com a obra do grande poeta latino americano Pablo Neruda. Trata-se de uma livre associação ao lançar um olhar sobre a teoria freudiana da angústia para vê-la caracterizada no poema “Vinte Poemas de Amor e Uma Canção Desesperada” de Pablo Neruda.

  3. Periodic solutions of delayed predator-prey model with the Beddington-DeAngelis functional response

    Energy Technology Data Exchange (ETDEWEB)

    Huo Haifeng [Institute of Applied Mathematics, Lanzhou University of Technology, Lanzhou, Gansu 730050 (China)]. E-mail: hfhuo@lut.cn; Li Wantong [Department of Mathematics, Lanzhou University Lanzhou, Gansu 730000 (China)]. E-mail: wtli@lzu.edu.cn; Nieto, Juan J. [Departamento de Analisis Matematico, Facultad de Matematicas, Universidad de Santiago de Compostela 15782 (Spain)]. E-mail: amnieto@usc.es

    2007-07-15

    By using the continuation theorem based on Gaines and Mawhin's coincidence degree, sufficient and realistic conditions are obtained for the global existence of positive periodic solutions for a delayed predator-prey model with the Beddington-DeAngelis functional response. Our results are applicable to state dependent and distributed delays.

  4. Angústia hipocondríaca e o eterno retorno do presente: considerações a partir do filme Sinédoque, New York

    Directory of Open Access Journals (Sweden)

    Thaís Klein

    Full Text Available Resumo A partir de questionamentos levantados pelo filme Sinédoque, New York (2008, pretende-se discutir a articulação da angústia hipocondríaca com a temporalidade. Observa-se que no filme o recurso do flashback não é utilizado; a temporalidade, que se instaura diante da angústia relacionada a sintomas hipocondríacos do personagem, calca-se em um presente absoluto. A hipocondria foi considerada por Freud uma neurose atual e a angústia a ela articulada opera como a contrapartida afetiva do encontro com o desamparo gerado pelo desfacelamento da imagem corporal. Estamos, portanto, diante da face traumática desse afeto que torna a ser discutido no contexto das neuroses traumáticas e mediante o conceito de angústia automática em 1926. A partir de então, a questão da atualidade dos sintomas, já indicada nas neuroses atuais, ganha um novo sentido: trata-se de uma problemática que não pôde ser representada e, por isso, insiste, instaurando eterno retorno do presente.

  5. Desenvolvimento e análise de compósitos cimentícios híbridos de alto desempenho

    Directory of Open Access Journals (Sweden)

    V. J. Ferrari

    Full Text Available Neste trabalho, estudou-se o efeito da hibridização em compósitos cimentícios numa tentativa de modificar o material em sua microestrutura e melhorar o processo de transferência de tensões da matriz cimentícia para as fibras de aço. Para tanto, fibras curtas e microfibras de aço foram adicionadas a uma matriz cimentícia de argamassa para confecção de corpos-de-prova prismáticos entalhados e com dimensões de 150 mm x 150 mm x 500 mm. Os corpos-de-prova foram submetidos a ensaios de flexão com carga no meio do vão sob o controle dos deslocamentos de abertura da entrada do entalhe (CMOD. O desempenho dos compósitos híbridos foi comparado ao dos compósitos produzidos somente com a adição da fibra curta de aço e também ao da matriz sem fibras. Os resultados foram analisados considerando-se os parâmetros de tenacidade flexional e tenacidade ao fraturamento do material. O processo de hibridização permitiu obter compósitos de alto desempenho.

  6. The impact of Mir-9 regulation in normal and malignant hematopoiesis

    Directory of Open Access Journals (Sweden)

    Abbas Khosravi

    2018-03-01

    Full Text Available MicroRNA-9 (MiR-9 dysregulation has been observed in various cancers. Recently, MiR-9 is considered to have a part in hematopoiesis and hematologic malignancies. However, its importance in blood neoplasms is not yet well defined. Thus, this study was conducted in order to assess the significance of MiR-9 role in the development of hematologic neoplasia, prognosis, and treatment approaches. We have shown that a large number of MiR-9 targets (such as FOXOs, SIRT1, CCND1, ID2, CCNG1, Ets, and NFkB play essential roles in leukemogenesis and that it is overexpressed in different leukemias. Our findings indicated MiR-9 downregulation in a majority of leukemias. However, its overexpression was reported in patients with dysregulated MiR-9 controlling factors (such as MLLr. Additionally, prognostic value of MiR-9 has been reported in some types of leukemia. This study generally emphasizes on the critical role of MiR-9 in hematologic malignancies as a prognostic factor and a therapeutic target.

  7. Enhanced activity of an angiotensin-(1-7) neuropeptidase in glucocorticoid-induced fetal programming.

    Science.gov (United States)

    Marshall, Allyson C; Shaltout, Hossam A; Pirro, Nancy T; Rose, James C; Diz, Debra I; Chappell, Mark C

    2014-02-01

    We previously identified angiotensin converting enzyme (ACE) and an endopeptidase activity that degraded angiotensin-(1-7) [Ang-(1-7)] to Ang-(1-5) and Ang-(1-4), respectively, in the cerebrospinal fluid (CSF) of 6-month old male sheep. The present study undertook a more comprehensive analysis of the CSF peptidase that converts Ang-(1-7) to Ang-(1-4) in control and in utero betamethasone-exposed sheep (BMX). Characterization of the Ang-(1-7) peptidase revealed that the thiol agents 4-aminophenylmercuric acetate (APMA) and p-chloromercuribenzoic acid (PCMB), as well as the metallo-chelators o-phenanthroline and EDTA essentially abolished the enzyme activity. Additional inhibitors for serine, aspartyl, and cysteine proteases, as well as selective inhibitors against the endopeptidases neprilysin, neurolysin, prolyl and thimet oligopeptidases did not attenuate enzymatic activity. Competition studies against the peptidase revealed similar IC50s for Ang-(1-7) (5μM) and Ang II (3μM), but lower values for Ala(1)-Ang-(1-7) and Ang-(2-7) of 1.8 and 2.0μM, respectively. In contrast, bradykinin exhibited a 6-fold higher IC50 (32μM) than Ang-(1-7) while neurotensin was a poor competitor. Mean arterial pressure (78±1 vs. 94±2mmHg, N=4-5, Pfetal programming. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Renal Bleeding Due to Extramedullary Hematopoiesis in a Patient With Chronic Myelogenous Leukemia

    OpenAIRE

    Stephanie Zettner; Sandeep G. Mistry

    2014-01-01

    Chronic myelogenous leukemia (CML) is a myeloproliferative disorder that normally presents in middle-aged adults. Renal infiltration and extramedullary hematopoiesis in renal tissue has been rarely reported. This case report presents a patient with CML and renal insufficiency who developed gross hematuria. Efforts at controlling the hematuria led to a cascade of events propelled by the underlying disorder that ultimately led to a radical nephrectomy, multiorgan failure, and prolonged hospital...

  9. Compósitos à base de gesso com resíduos de EVA e vermiculita

    OpenAIRE

    Oliveira,Marilia P. de; Barbosa,Normando P.; Torres,Sandro M.; Leal,Antonio F.; Silva,Cibelle G.

    2012-01-01

    O gesso é um dos materiais de construção mais antigos de que se tem conhecimento. Algumas de suas propriedades lhes conferem vantagens, tais como resistência ao fogo e isolamentos térmico e acústico. Objetivou-se, com este trabalho, avaliar as propriedades físico-mecânicas de compósitos à base de gesso com a incorporação de resíduos da indústria de calçados, o etileno acetato de vinila (EVA) e a vermiculita. O desenvolvimento desses compósitos tem como propósito a produção de elementos de rev...

  10. A model for economic evaluation of the use of Adsorbed Natural Gas (ANG); Modelo de avaliacao economica do uso do Gas Natural Adsorvido (GNA)

    Energy Technology Data Exchange (ETDEWEB)

    Azevedo, Diana C.S.; Cavalcante Junior, Celio L.; Torres, A. Eurico B.; Oliveira Junior, Jose A.; Medeiros, Vanildo M. de [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil); Campos, Flavio B.; Moura, Newton R. de [PETROBRAS, Rio de Janeiro, RJ (Brazil). Centro de Pesquisas (CENPES). Gerencia de Gas e Energia; Campos, Michel F. [PETROBRAS, Rio de Janeiro, RJ (Brazil). Gerencia de Tecnologia de Gas e Energia; Alexandre, Francisco de Assis Souza

    2004-07-01

    Natural gas is currently transported by two main ways: through pipelines and stored in reservoirs, under compressed (CNG) or liquefied (LNG) forms. Adsorbed natural gas (ANG) is a third alternative to vessel storage, which has been intensively reported in the scientific and technical literature. Working pressures are considerably lower for ANG (3,5 MPa as compared to 25 MPa for CNG), which results in lower costs with vessel construction and compression and safer handling. The project ADSPOR, sponsored by PETROBRAS and part of the R and D portfolio of RedeGasEnergia, aims to assess the technical and economical feasibility of storing and transporting natural gas confined in carbon adsorbents. The objectives of this project are the production of high-capacity active carbons, the collection of adsorption data for NG storage and the economic evaluation of ANG. The present work presents a model for cost estimation of the ANG business, which comprises from the compression into ANG vessels until the distribution to the final costumer, taking into account several shipping modes. The variables involved in the model were: compression costs, equipment and materials technical data, costs with product handling and shipping costs for motor ways, railways and inland waterways. These variables were linked so as to generate a cost matrix that may be used to assess investment and calculate the final cost for GNA transport. The model may be used to carry out parameter sensitivity analysis, for decision-making and management purposes. (author)

  11. NLP pielietošana angļu valodas mācīšanā

    OpenAIRE

    Gorohova, Diāna

    2011-01-01

    Neirolingvistiskās programmēšana (NLP) praktiķu aprindās tiek uzskatīta par ļoti efektīvu instrumentu visdažādākajās dzīves sfēras. Šī pieeja ļauj cilvēkiem ticēt saviem spēkiem padarīt viņu dzīves labākas. Tieši tāpēc NLP piekritēji uzskata, ka, NLP pieeju izmantošana angļu valodas mācīšanā, var uzlabot skolēnu angļu valodas zināšanas, kā arī paaugstināt viņu pašapziņu. Šī bakalaura darba autore piedāvā ieskatu NLP vēsturiskajā attīstībā un apskata tās pamatprincipus. Autore analizē NLP t...

  12. Wnt signaling controls the specification of definitive and primitive hematopoiesis from human pluripotent stem cells.

    Science.gov (United States)

    Sturgeon, Christopher M; Ditadi, Andrea; Awong, Geneve; Kennedy, Marion; Keller, Gordon

    2014-06-01

    Efforts to derive hematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) are complicated by the fact that embryonic hematopoiesis consists of two programs, primitive and definitive, that differ in developmental potential. As only definitive hematopoiesis generates HSCs, understanding how this program develops is essential for being able to produce this cell population in vitro. Here we show that both hematopoietic programs transition through hemogenic endothelial intermediates and develop from KDR(+)CD34(-)CD144(-) progenitors that are distinguished by CD235a expression. Generation of primitive progenitors (KDR(+)CD235a(+)) depends on stage-specific activin-nodal signaling and inhibition of the Wnt-β-catenin pathway, whereas specification of definitive progenitors (KDR(+)CD235a(-)) requires Wnt-β-catenin signaling during this same time frame. Together, these findings establish simple selective differentiation strategies for the generation of primitive or definitive hematopoietic progenitors by Wnt-β-catenin manipulation, and in doing so provide access to enriched populations for future studies on hPSC-derived hematopoietic development.

  13. COX2 inhibition during nephrogenic period induces ANG II hypertension and sex-dependent changes in renal function during aging.

    Science.gov (United States)

    Reverte, Virginia; Tapia, Antonio; Loria, Analia; Salazar, Francisco; Llinas, M Teresa; Salazar, F Javier

    2014-03-01

    This study was performed to test the hypothesis that ANG II contributes to the hypertension and renal functional alterations induced by a decrease of COX2 activity during the nephrogenic period. It was also examined whether renal functional reserve and renal response to volume overload and high sodium intake are reduced in 3-4- and 9-11-mo-old male and female rats treated with vehicle or a COX2 inhibitor during nephrogenic period (COX2np). Our data show that this COX2 inhibition induces an ANG II-dependent hypertension that is similar in male and female rats. Renal functional reserve is reduced in COX2np-treated rats since their renal response to an increase in plasma amino acids levels is abolished, and their renal ability to eliminate a sodium load is impaired (P renal excretory ability is similar in both sexes during aging but does not induce the development of a sodium-sensitive hypertension. However, the prolonged high-sodium intake at 9-11 mo of age leads to a greater proteinuria in male than in female (114 ± 12 μg/min vs. 72 ± 8 μg/min; P Renal hemodynamic sensitivity to acute increments in ANG II is unaltered in both sexes and at both ages in COX2np-treated rats. In summary, these results indicate that the reduction of COX2 activity during nephrogenic period programs for the development of an ANG II-dependent hypertension, reduces renal functional reserve to a similar extent in both sexes, and increases proteinuria in males but not in females when there is a prolonged increment in sodium intake.

  14. Phytoremediation of 1,4-dioxane-containing recovered groundwater.

    Science.gov (United States)

    Ferro, Ari M; Kennedy, Jean; LaRue, James C

    2013-01-01

    The results of a pilot-scale phytoremediation study are reported in this paper. Small plots of trees established on a closed municipal waste landfill site were irrigated with recovered groundwater containing 1,4-dioxane (dioxane) and other volatile organic compounds (VOCs). The plots were managed to minimize the leaching of irrigation water, and leaching was quantified by the use of bromide tracer. Results indicated that the dioxane (2.5 microg/L) was effectively removed, probably via phytovolatilization, and that a full-scale phytoremediation system could be used. A system is now in place at the site in which the recovered groundwater can be treated using two different approaches. A physical treatment system (PTS) will be used during the winter months, and a 12 ha phytoremediation system (stands of coniferous trees) will be used during the growing season. The PTS removes VOCs using an air-stripper, and destroys dioxane using a photo-catalytic oxidation process. Treated water will be routed to the local sewer system. The phytoremediation system, located on the landfill, will be irrigated with effluent from the PTS air-stripper containing dioxane. Seasonal use of the phytoremediation system will reduce reliance on the photo-catalytic oxidation process that is extremely energy consumptive and expensive to operate.

  15. Angiopoietin-2/angiopoietin-1 as non-invasive biomarker of cirrhosis in chronic hepatitis C

    Science.gov (United States)

    Hernández-Bartolomé, Ángel; López-Rodríguez, Rosario; Borque, María Jesús; González-Moreno, Leticia; Real-Martínez, Yolanda; García-Buey, Luisa; Moreno-Otero, Ricardo; Sanz-Cameno, Paloma

    2016-01-01

    AIM To evaluate the efficacy of peripheral blood concentrations of angiopoietins (Ang) as cirrhosis biomarkers of chronic hepatitis C (CHC). METHODS Ang1 and Ang2 serum levels were measured by enzyme-linked immunosorbent assays (ELISA) in samples from 179 cirrhotic and non-cirrhotic CHC patients, classified according to the METAVIR system. Groups were compared by non-parametric Mann-Whitney U test. Subsequently, the association of peripheral concentrations of angiopoietins with the stage of fibrosis was analyzed using Spearman correlation test. Finally, the accuracy, sensitivity and specificity of circulating angiopoietins for cirrhosis diagnosis were determined by the study of the respective area under the curve of receiver operator characteristics (AUC-ROC). RESULTS Peripheral blood concentrations of Ang1 and Ang2 in CHC patients were significantly related to fibrosis. While Ang1 was decreased in cirrhotic subjects compared to non-cirrhotic (P < 0.0001), Ang2 was significantly increased as CHC progressed to the end stage of liver disease (P < 0.0001). Consequently, Ang2/Ang1 ratio was notably amplified and significantly correlated with fibrosis (P < 0.0001). Interestingly, the individual performance of each angiopoietin for the diagnosis of cirrhosis reached notable AUC-ROC values (above 0.7, both), but the Ang2/Ang1 ratio was much better (AUC-ROC = 0.810) and displayed outstanding values of sensitivity (71%), specificity (84%) and accuracy (82.1%) at the optimal cut-off (10.33). Furthermore, Ang2/Ang1 ratio improved the performance of many other previously described biomarkers or scores of liver cirrhosis in CHC. CONCLUSION Ang2/Ang1 ratio might constitute a useful tool for monitoring the progression of chronic liver disease towards cirrhosis and play an important role as therapeutic target. PMID:27956798

  16. Entre angústia e desamparo

    Directory of Open Access Journals (Sweden)

    Jacques André

    2001-12-01

    Full Text Available Em sua discussão, o autor diz que a angústia é o motor da análise e de seu progresso: em si mesma é abertura para os enigmas do interior. O desamparo, por sua vez, indica que a vida psíquica continua a ser vivida fora de si, na desesperada abertura para um outro que não responde. Então, na análise, se uma mobiliza, o outro paralisa. O amor (compreendido em sua parte não narcísica é "agarrar-se" aos objetos do mundo exterior, é abertura mantida para o outro e, nesse ponto, homogênea do estado de desamparo do bebê.Between anxiety and helplessness. In this paper the author states that anxiety is the engine of both analysis and its progress: in itself it is an opening to the puzzles of the interior. Helplessness, on the other hand, points out that psychic life is still being lived out of oneself, in a desperate opening to an unresponsive other. So, under the analysis point of view, while one mobilizes, the other paralyses. Love (out of its narcissistic part is "to cling" to objects of the external world, it is an opening to the other and, at that point, homogeneous to the baby's state of helplessness.

  17. Entre structure et action : la compétence communicative des TIC

    Directory of Open Access Journals (Sweden)

    Serge Agostinelli

    2011-06-01

    Full Text Available Cet article théorique explore comment les concepts de structure et d’action permettent une approche originale du concept de compétence dans le domaine des TIC. Cette approche relève d’une recherche de compatibilité entre des modèles issus des Technologies qui proposent les structures socio-techniques et ceux des Sciences Humaines qui organisent l’action des individus. Les modèles théoriques invoqués de domaines disciplinaires différents (sociologie, ethnométhodologie, psychologie sociale, linguistique, sciences de l’éducation et sciences de l’information-communication donnent au concept de compétence en TIC une nouvelle consistance, plus anthropocentrée et moins technico-pratique. Ils posent la question du rapport entre micro et macro, du rapport de l’individu au groupe, et posent aussi la question ontologique des structures. Les compétences ne se réduisent pas à la seule connaissance des aspects techniques, mais sont élargies à la maîtrise des conditions d’utilisation adéquate et des possibilités offertes par la technique. Utiliser les technologies, c’est construire de la relation grâce aux compétences communicatives des TIC.This theoretical article investigates how the concepts of structure and action allow an original approach of the concept of skill in the field of ICT. This approach concerns a search for compatibility between stemming models Technologies which propose the socio-technical structures and those of the Human Sciences who organize the action of the individuals. The theoretical models called by different disciplinary domains (sociology, ethnomethodology, social psychology, linguistic, education, communication and information science give to the concept of skill in ICT a new consistency, more anthropology centred and less technico-practical. They ask the question of the relationship between micro and macro, the relationship of the individual to the group, and also ask the ontological question

  18. La transmission efficace des compétences via Internet : exemple pratique

    NARCIS (Netherlands)

    Caniëls, M.C.J.

    2005-01-01

    Les universités sont de plus en plus nombreuses à adopter des modèles pédagogiques novateurs, plutôt axés sur le développement des compétences que sur la reproduction des connaissances. Ces nouveaux modèles pédagogiques soulignent l’importance de la mise en application des connaissances et du

  19. Angiopoietin1 inhibits mast cell activation and protects against anaphylaxis.

    Directory of Open Access Journals (Sweden)

    Jun-Hua Yao

    Full Text Available Since morbidity and mortality rates of anaphylaxis diseases have been increasing year by year, how to prevent and manage these diseases effectively has become an important issue. Mast cells play a central regulatory role in allergic diseases. Angiopoietin1 (Ang-1 exhibits anti-inflammatory properties by inhibiting vascular permeability, leukocyte migration and cytokine production. However, Ang-1's function in mast cell activation and anaphylaxis diseases is unknown. The results of our study suggest that Ang-1 decreased lipopolysaccharide (LPS-induced pro-inflammatory cytokines production of mast cells by suppressing IκB phosphorylation and NF-κB nuclear translocation. Ang-1 also strongly inhibited compound 48/80 induced and FcεRI-mediated mast cells degranulation by decreasing intracellular calcium levels in vitro. In vivo lentivirus-mediated delivery of Ang-1 in mice exhibited alleviated leakage in IgE-dependent passive cutaneous anaphylaxis (PCA. Furthermore, exogenous Ang-1 intervention treatment prevented mice from compound 48/80-induced mesentery mast cell degranulation, attenuated increases in pro-inflammatory cytokines, relieved lung injury, and improved survival in anaphylaxis shock. The results of our study reveal, for the first time, the important role of Ang-1 in the activation of mast cells, and identify a therapeutic effect of Ang-1 on anaphylaxis diseases.

  20. CompTIA A+ certification all-in-one for dummies

    CERN Document Server

    Clarke, Glen E

    2012-01-01

    Comprehensive coverage of everything you must know to pass CompTIA's A+ exam A+ is the gateway certification into many IT careers, and interest in certification is exploding. This bestselling A+ certification guide is updated to cover the new A+ exam. It includes the new Windows coverage and reflects the revised emphasis on objectives. Nine minibooks focus individually on specific hardware and OS characteristics including installation and configuration, diagnostics, preventive maintenance, motherboard and processors, printers, networking, and fundamentals. A companion website contains the popu

  1. Cord Compression due to Extramedullary Hematopoiesis in an Adolescent with Known Beta Thalassemia Major

    OpenAIRE

    Soman, Salil; Rosenfeld, David L; Roychowdhury, Sudipta; Drachtman, Richard A; Cohler, Alan

    2009-01-01

    We describe a 16 year-old male with ß thalassemia major and gait disturbances that had not been given blood transfusions due to a severe childhood transfusion reaction. Thoracic spine MRI demonstrated hematopoietic marrow throughout the spine and epidural masses causing cord compression consistent with extramedullary hematopoiesis (EMH). After treatment with steroids, radiotherapy and monitored blood transfusions, the patient demonstrated significant improvement of his paraspinal lesions a...

  2. A mouse model for Costello syndrome reveals an Ang II–mediated hypertensive condition

    Science.gov (United States)

    Schuhmacher, Alberto J.; Guerra, Carmen; Sauzeau, Vincent; Cañamero, Marta; Bustelo, Xosé R.; Barbacid, Mariano

    2008-01-01

    Germline activation of H-RAS oncogenes is the primary cause of Costello syndrome (CS), a neuro-cardio-facio-cutaneous developmental syndrome. Here we describe the generation of a mouse model of CS by introduction of an oncogenic Gly12Val mutation in the mouse H-Ras locus using homologous recombination in ES cells. Germline expression of the endogenous H-RasG12V oncogene, even in homozygosis, resulted in hyperplasia of the mammary gland. However, development of tumors in these mice was rare. H-RasG12V mutant mice closely phenocopied some of the abnormalities observed in patients with CS, including facial dysmorphia and cardiomyopathies. These mice also displayed alterations in the homeostasis of the cardiovascular system, including development of systemic hypertension, extensive vascular remodeling, and fibrosis in both the heart and the kidneys. This phenotype was age dependent and was a consequence of the abnormal upregulation of the renin–Ang II system. Treatment with captopril, an inhibitor of Ang II biosynthesis, prevented development of the hypertension condition, vascular remodeling, and heart and kidney fibrosis. In addition, it partially alleviated the observed cardiomyopathies. These mice should help in elucidating the etiology of CS symptoms, identifying additional defects, and evaluating potential therapeutic strategies. PMID:18483625

  3. Intracranial involvement in extramedullary hematopoiesis: case report and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Haidar, Salwa; Ortiz-Neira, Clara; Shroff, Manohar; Gilday, David; Blaser, Susan [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada)

    2005-06-01

    Intracranial involvement in extramedullary hematopoiesis (EMH) is rare, but it should be suspected in patients with myelofibrosis presenting with chronic severe headache. We present a 9-year-old girl with known myelofibrosis whose headaches were unresponsive to routine treatment. CT and MRI studies of the brain showed diffuse pachymeningeal thickening. CT examinations of the chest and abdomen had demonstrated bilateral thoracic paraspinal masses caused by EMH, suggesting the possibility that the intracranial involvement might also be related to EMH. The diagnosis was confirmed by sulfur colloid isotope scan. (orig.)

  4. Intracranial involvement in extramedullary hematopoiesis: case report and review of the literature

    International Nuclear Information System (INIS)

    Haidar, Salwa; Ortiz-Neira, Clara; Shroff, Manohar; Gilday, David; Blaser, Susan

    2005-01-01

    Intracranial involvement in extramedullary hematopoiesis (EMH) is rare, but it should be suspected in patients with myelofibrosis presenting with chronic severe headache. We present a 9-year-old girl with known myelofibrosis whose headaches were unresponsive to routine treatment. CT and MRI studies of the brain showed diffuse pachymeningeal thickening. CT examinations of the chest and abdomen had demonstrated bilateral thoracic paraspinal masses caused by EMH, suggesting the possibility that the intracranial involvement might also be related to EMH. The diagnosis was confirmed by sulfur colloid isotope scan. (orig.)

  5. A Rare Presentation of Extramedullary Hematopoiesis in Post-polycythemic Myelofibrosis.

    Science.gov (United States)

    Konca Degertekin, Ceyla; Ozkurt, Zübeyde Nur; Akyürek, Nalan; Yağcı, Münci

    2014-09-01

    Polycythemia vera is a clonal proliferative disorder of the bone marrow that could possibly evolve into myelofibrosis in its natural course. Progression to myelofibrosis is usually a late stage complication and presents clinically with refractory cytopenias and extramedullary hematopoiesis (EMH). EMH can occur in any tissue during the course of post-polycythemic myelofibrosis. However, skin and cardiac involvements seems to be very rare. We present a 56-year-old woman with post-polycythemic myelofibrosis refractory to treatment, developing EMH after splenectomy in various organs, exceptionally the skin and the heart. Along with the case, the clinical presentations, treatment options, prognostic significance of EMH and the role of cytogenetics is discussed in the light of the literature.

  6. CompTIA network+ study guide exam N10-006

    CERN Document Server

    Lammle, Todd

    2015-01-01

    All-star N10-006 prep, fully updated for the new exam The CompTIA Network+ Study Guide is your one-stop comprehensive resource in preparing for exam N10-006 Bestselling author and networking Guru Todd Lammle guides you through 100% of all exam objectives detailing the fundamental concepts you will need to know to prepare for the exam. Coverage includes network technologies, installation and configuration, media and topologies, security, and much more, plus practical examples drawn from real-world situations. You also gain access to practice exams and electronic flashcards that facilitate info

  7. Role of Vitamin A/Retinoic Acid in Regulation of Embryonic and Adult Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Ana Cañete

    2017-02-01

    Full Text Available Vitamin A is an essential micronutrient throughout life. Its physiologically active metabolite retinoic acid (RA, acting through nuclear retinoic acid receptors (RARs, is a potent regulator of patterning during embryonic development, as well as being necessary for adult tissue homeostasis. Vitamin A deficiency during pregnancy increases risk of maternal night blindness and anemia and may be a cause of congenital malformations. Childhood Vitamin A deficiency can cause xerophthalmia, lower resistance to infection and increased risk of mortality. RA signaling appears to be essential for expression of genes involved in developmental hematopoiesis, regulating the endothelial/blood cells balance in the yolk sac, promoting the hemogenic program in the aorta-gonad-mesonephros area and stimulating eryrthropoiesis in fetal liver by activating the expression of erythropoietin. In adults, RA signaling regulates differentiation of granulocytes and enhances erythropoiesis. Vitamin A may facilitate iron absorption and metabolism to prevent anemia and plays a key role in mucosal immune responses, modulating the function of regulatory T cells. Furthermore, defective RA/RARα signaling is involved in the pathogenesis of acute promyelocytic leukemia due to a failure in differentiation of promyelocytes. This review focuses on the different roles played by vitamin A/RA signaling in physiological and pathological mouse hematopoiesis duddurring both, embryonic and adult life, and the consequences of vitamin A deficiency for the blood system.

  8. Angiotensin II Regulates Th1 T Cell Differentiation Through Angiotensin II Type 1 Receptor-PKA-Mediated Activation of Proteasome.

    Science.gov (United States)

    Qin, Xian-Yun; Zhang, Yun-Long; Chi, Ya-Fei; Yan, Bo; Zeng, Xiang-Jun; Li, Hui-Hua; Liu, Ying

    2018-01-01

    Naive CD4+ T cells differentiate into T helper cells (Th1 and Th2) that play an essential role in the cardiovascular diseases. However, the molecular mechanism by which angiotensin II (Ang II) promotes Th1 differentiation remains unclear. The aim of this study was to determine whether the Ang II-induced Th1 differentiation regulated by ubiquitin-proteasome system (UPS). Jurkat cells were treated with Ang II (100 nM) in the presence or absence of different inhibitors. The gene mRNA levels were detected by real-time quantitative PCR analysis. The protein levels were measured by ELISA assay or Western blot analysis, respectively. Ang II treatment significantly induced a shift from Th0 to Th1 cell differentiation, which was markedly blocked by angiotensin II type 1 receptor (AT1R) inhibitor Losartan (LST). Moreover, Ang II significantly increased the activities and the expression of proteasome catalytic subunits (β1, β1i, β2i and β5i) in a dose- and time-dependent manner. However, Ang II-induced proteasome activities were remarkably abrogated by LST and PKA inhibitor H-89. Mechanistically, Ang II-induced Th1 differentiation was at least in part through proteasome-mediated degradation of IκBα and MKP-1 and activation of STAT1 and NF-κB. This study for the first time demonstrates that Ang II activates AT1R-PKA-proteasome pathway, which promotes degradation of IκBα and MKP-1 and activation of STAT1 and NF-κB thereby leading to Th1 differentiation. Thus, inhibition of proteasome activation might be a potential therapeutic target for Th1-mediated diseases. © 2018 The Author(s). Published by S. Karger AG, Basel.

  9. L’Angélus dans la boîte à lettres*

    OpenAIRE

    Jr, William A. Christian; Mittermaier, Amira

    2015-01-01

    En France, la popularité des cartes postales inspirées de L’Angélus de Jean-François Millet coïncide avec les débats publics qui ont accompagné la promulgation de la loi Combes de 1905. À partir des centaines de cartes accessibles sur le site internet de vente aux enchères Delcampe, les auteurs étudient les messages portés par les cartes, recensent le sexe des correspondants (majoritairement des femmes), et comparent les nombreuses images qui rejouent le couple en prière dans un champ. Aux di...

  10. Effects of angiopoietin-1 on inflammatory injury in endothelial progenitor cells and blood vessels.

    Science.gov (United States)

    Wang, Yi-Qing; Song, Jing-Jin; Han, Xiao; Liu, Yi-Ye; Wang, Xi-Huang; Li, Zhi-Ming; Tzeng, Chi-Meng

    2014-01-01

    Endothelial progenitor cells (EPCs) and angiopoietin-1 (Ang-1) play important roles in vasculogenesis and angiogenesis, respectively. Thus, targeting both aspects of cardiovascular tissue regeneration may offer promising therapeutic options for cardiovascular disorders. To this end, we constructed a lentiviral vector (pNL) with the Ang-1 gene and transfected EPCs with it (Ang-1-EPCs) to investigate vasculogenesis in both cellular and animal models. Compared to controls, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) increased significantly in both untreated EPCs and in the pNL vector group. After Ang-1 transcription, ICAM-1 and VCAM-1 decreased considerably in those treatment groups. Ang-1-modified EPCs alleviated inflammatory responses induced by tumor-necrosis factor-α (TNF-α) in vitro. Moreover, Ang-1-EPC implantation inhibited neointimal hyperplasia after balloon catheter injury in rats, dramatically diminishing the intimal-media (I/M) ratio and decreasing the neointimal area. Proliferating cell nuclear antigen expression in the Ang-1-EPC group was lower than the EPC non-treatment group as well, suggesting that Ang-1-EPC improved cell survival during inflammation and promoted endothelialization in damaged blood vessels.

  11. Intelligence économique, compétitivité et cohésion sociale

    Directory of Open Access Journals (Sweden)

    Luc Marie Quoniam

    2005-12-01

    Full Text Available Book review: Intelligence économique, compétitivité et cohésion sociale by Bernard Carayon (.pdf rapportPublished by: Ministère de l’Intérieur français Année d'édition : 2003 Réf. : 9782110054913, 176 pages, 21x29,7 cm ISBN : 2-11-005491-3

  12. Análise da influência do traço nas propriedades do compósito cimento-madeira

    Directory of Open Access Journals (Sweden)

    Alessandra Monique Weber

    2017-08-01

    Full Text Available Os compósitos de cimento com adição de madeira apresentam vantagens, quando comparados a outros materiais convencionais da construção civil, como resistência à água, ao fogo e aos agentes deterioradores. Um dos obstáculos para o uso desse compósito é a inibição causada pela madeira na cura do cimento, devido aos componentes da madeira afetarem as reações, tendo como consequência um compósito de baixa qualidade. Dessa forma, este trabalho teve por objetivo avaliar diferentes traços do compósito cimento-madeira, utilizando resíduos de Pinus spp., por meio de ensaios de laboratório. Foi utilizado o cimento Portland CP II Z 32, relação água/cimento igual a 0,4; o aditivo químico escolhido foi o cloreto de cálcio para acelerar a pega. Para a comparação de desempenho, foram delimitadas quatro dosagens diferentes, com teores de adição de madeira de 10%, 20%, 25% e 33% em relação à massa de cimento. Para a análise, foram feitos ensaios das propriedades físicas e mecânicas para todas as dosagens, sendo, posteriormente, submetidas à análise da variância e teste de Tukey. Os resultados dos ensaios das propriedades físicas e mecânicas dos compósitos demonstraram que, para as relações escolhidas, quanto menor for a adição de madeira melhores serão os resultados das propriedades, mas mesmo os traços com maiores teores de madeira apresentam resultados relevantes, atentando-se apenas para o fato da relação água/cimento ser baixa para os casos analisados, e, devido a isso, ter influenciado negativamente nos resultados.

  13. Impact of angiotensin II on skeletal muscle metabolism and function in mice: contribution of IGF-1, Sirtuin-1 and PGC-1α.

    Science.gov (United States)

    Kackstein, Katharina; Teren, Andrej; Matsumoto, Yasuharu; Mangner, Norman; Möbius-Winkler, Sven; Linke, Axel; Schuler, Gerhard; Punkt, Karla; Adams, Volker

    2013-05-01

    Activation of the renin-angiotensin-aldosterone system and increased levels of angiotensin II (Ang-II) occurs in numerous cardiovascular diseases such as chronic heart failure (CHF). Another hallmark in CHF is a reduced exercise tolerance with impaired skeletal muscle function. The aim of this study was to investigate in an animal model the impact of Ang-II on skeletal muscle function and concomitant molecular alterations. Mice were infused with Ang-II for 4 weeks. Subsequently, skeletal muscle function of the soleus muscle was assessed. Expression of selected proteins was quantified by qRT-PCR and Western blot. Infusion of Ang-II resulted in a 33% reduction of contractile force, despite a lack of changes in muscle weight. At the molecular level an increased expression of NAD(P)H oxidase and a reduced expression of Sirt1, PGC-1α and IGF-1 were noticed. No change was evident for the ubiquitin E3-ligases MuRF1 and MafBx and α-sarcomeric actin expression. Cytophotometrical analysis of the soleus muscle revealed a metabolic shift toward a glycolytic profile. This study provides direct evidence of Ang-II-mediated, metabolic deterioration of skeletal muscle function despite preserved muscle mass. One may speculate that the Ang-II-mediated loss of muscle force is due to an activation of NAD(P)H oxidase expression and a subsequent ROS-induced down regulation of IGF-1, PGC-1α and Sirt1. Copyright © 2012 Elsevier GmbH. All rights reserved.

  14. Favorable Vascular Actions of Angiotensin-(1-7) in Human Obesity.

    Science.gov (United States)

    Schinzari, Francesca; Tesauro, Manfredi; Veneziani, Augusto; Mores, Nadia; Di Daniele, Nicola; Cardillo, Carmine

    2018-01-01

    Obese patients have vascular dysfunction related to impaired insulin-stimulated vasodilation and increased endothelin-1-mediated vasoconstriction. In contrast to the harmful vascular actions of angiotensin (Ang) II, the angiotensin-converting enzyme 2 product Ang-(1-7) has shown to exert cardiovascular and metabolic benefits in experimental models through stimulation of the Mas receptor. We, therefore, examined the effects of exogenous Ang-(1-7) on vasodilator tone and endothelin-1-dependent vasoconstriction in obese patients. Intra-arterial infusion of Ang-(1-7) (10 nmol/min) resulted in significant increase in unstimulated forearm flow ( P =0.03), an effect that was not affected by the Mas receptor antagonist A779 (10 nmol/min; P >0.05). In the absence of hyperinsulinemia, however, forearm flow responses to graded doses of acetylcholine and sodium nitroprusside were not different during Ang-(1-7) administration compared with saline (both P >0.05). During infusion of regular insulin (0.15 mU/kg per minute), by contrast, endothelium-dependent vasodilator response to acetylcholine was significantly enhanced by Ang-(1-7) ( P =0.04 versus saline), whereas endothelium-independent response to sodium nitroprusside was not modified ( P =0.91). Finally, Ang-(1-7) decreased the vasodilator response to endothelin A receptor blockade (BQ-123; 10 nmol/min) compared with saline (6±1% versus 93±17%; P obese patients Ang-(1-7) has favorable effects not only to improve insulin-stimulated endothelium-dependent vasodilation but also to blunt endothelin-1-dependent vasoconstrictor tone. These findings provide support for targeting Ang-(1-7) to counteract the hemodynamic abnormalities of human obesity. © 2017 American Heart Association, Inc.

  15. Association of plasma angiotensin-(1-7 level and left ventricular function in patients with type 2 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Pan-Pan Hao

    Full Text Available We recently found that overexpression of angiotensin (Ang-converting enzyme 2, which metabolizes Ang-II to Ang-(1-7 and Ang-I to Ang-(1-9, may prevent diabetes-induced left ventricular remodeling and dysfunction in rats. Our objective was to evaluate the association of plasma Ang-(1-7 level and left ventricular function in patients with type 2 diabetes mellitus.We measured the left ventricular ejection fraction (EF, ratio of early to late left ventricular filling velocity (E/A and ratio of early diastolic mitral inflow to annular velocity (E/Ea by ultrasonography in 110 patients with type 2 diabetes mellitus for more than 5 years. Anthropometric and fasting blood values were obtained from medical records. The plasma Ang-(1-7 level in patients with a poor EF (15 was significantly lower than that in patients with E/Ea ≤15. Ang-(1-7 level was negatively correlated with E/Ea and Log-N-terminal pro-B-type natriuretic peptide and positively with EF and E/A. Stepwise multiple regression analysis revealed that Ang-(1-7, hemoglobin A1c and Ang-II levels as well as duration of diabetes predicted EF; Ang-(1-7 level, fasting blood glucose, low-density lipoprotein cholesterol level and duration of diabetes predicted E/A; and Ang-(1-7 and hemoglobin A1c levels predicted E/Ea.Plasma Ang-(1-7 level is independently associated with left ventricular function in patients with type 2 diabetes mellitus and may be a biomarker for assessing cardiac function in such patients.

  16. Developing Consensus on the CompHP Professional Standards for Health Promotion in Europe

    Science.gov (United States)

    Speller, Viv; Parish, Richard; Davison, Heather; Zilnyk, Anna

    2012-01-01

    Building on the CompHP Core Competencies for health promotion the Professional Standards for Health Promotion have been developed and consulted on across Europe. The standards were formulated to fit within the complexity of professional, occupational and educational standards frameworks in Europe as learning outcome standards with performance…

  17. The human protooncogene product p33pim is expressed during fetal hematopoiesis and in diverse leukemias

    International Nuclear Information System (INIS)

    Amson, R.; Przedborski, S.; Telerman, A.; Sigaux, F.; Flandrin, G.; Givol, D.

    1989-01-01

    The authors measured the human pim-1 protooncogene (PIM) expression during fetal development and in hematopoietic malignancies. The data indicate that during human fetal hematopoiesis the 33-kDa pim product, p33pim, is highly expressed in the liver and the spleen. In contrast, a the adult stage it is only slightly expressed in circulating granulocytes. Out of 70 hematopoietic malignancies analyzed, 51 patients and 19 cell lines, p33pim was overexpressed in ∼ 30% of the samples, particularly in myeloid and lymphoid acute leukemias. This overexpression was unrelated to any stage of cellular differentiation and was not due to gene rearrangement or amplification. These results imply a physiological role of the pim-1 protooncogene during hematopoietic development and a deregulation in various leukemias

  18. Sympatho-inhibitory properties of various AT1 receptor antagonists

    NARCIS (Netherlands)

    Balt, Jippe C.; Mathy, Marie-Jeanne; Pfaffendorf, Martin; van Zwieten, Peter A.

    2002-01-01

    It is well known that angiotensin II (Ang II) can facilitate the effects of sympathetic neurotransmission. In the present study, using various experimental models, we investigated the inhibitory effects of several Ang II subtype 1 receptor (AT1) antagonists on this Ang II-induced facilitation. We

  19. Liberación de endotelina-1 por angiotensina ll en miocitos cardíacos aislados Angiotensin II-induced endothelin-1 release in cardiac myocytes

    Directory of Open Access Journals (Sweden)

    María C. Villa-Abrille

    2006-06-01

    Full Text Available Muchos de los efectos de la angiotensina II (Ang II son mediados en realidad por la acción de endotelina (ET endógena liberada y/o producida en respuesta a la Ang II. En este trabajo evaluamos la interacción Ang II/ET-1, sus consecuencias en la contractilidad cardíaca y el papel de las especies reactivas del oxígeno (EROs. Se usaron cardiomiocitos aislados de gato. La Ang II, 1 nM, produjo un efecto inotrópico positivo (EIP de 31.8±3.8% que fue cancelado por inhibición de los receptores AT1, de los receptores de ET, del intercambiador Na+/H+ (NHE, del modo inverso del intercambiador Na+/Ca2+ (NCX o por el secuestro de EROs. La Ang II, 100 nM, produjo un EIP de 70.5±7.6% que fue cancelado por inhibición de los receptores AT1 y bloqueado en parte por inhibición de los receptores de ET, del NHE, del modo inverso del NCX o por el secuestro de EROs. La Ang II, 1 nM, incrementó el ARNm de la preproET-1 lo cual fue anulado por el bloqueo de los receptores AT1. Los resultados permiten concluir que el EIP de la Ang II es debido a la acción de la ET-1 endógena liberada/formada por la Ang II. La ET-1 produce: estimulación del NHE, activación del modo inverso del NCX y un consecuente EIP. Dentro de esta cascada también participarían los EROs.Many of the effects thought to be due to angiotensin II (Ang II are due to the release/formation of endothelin (ET. We tested whether Ang II elicits its positive inotropic effect (PIE by the action of endogenous ET-1 and the role played by the reactive oxygen species (ROS in this mechanism. Experiments were performed in cat isolated ventricular myocytes in which sarcomere shortening (SS was measured to asses contractility after pharmacological interventions and the effect of Ang II on inotropism were analyzed. Ang II 1 nM increased SS by 31.8±3.8% (p<0.05. This PIE was cancelled by AT1 receptor blockade, by ET-1 receptors blockade, by Na+/H+ exchanger (NHE inhibition, by reverse mode Na+/Ca2

  20. Ectopic extramedullary hematopoiesis: evaluation and treatment of a rare and benign paraspinal/epidural tumor.

    Science.gov (United States)

    Mattei, Tobias A; Higgins, Michael; Joseph, Flynn; Mendel, Ehud

    2013-03-01

    Ectopic extramedullary hematopoiesis (EMH), defined as the formation of blood cells outside the bone marrow, usually occurs in a scenario of chronic anemia when, even after conversion of the bony yellow marrow to red marrow, the body is still unable to meet the demand for red blood cells. Ectopic extramedullary hematopoiesis most commonly occurs in the liver and spleen but may, in fact, occur almost anywhere in the body. Although previous reports have documented EMH presenting as paraspinal masses, such lesions have almost always been associated with a predisposing hematological disorder such as hemolytic anemia, myelofibrosis or myelodysplastic syndromes, thalassemia, polycythemia vera, leukemia, or lymphoma. The authors of this report describe the first reported instance of EMH in a patient presenting with a symptomatic epidural and paraspinal cervical lesion arising from the posterior spinal elements and no known predisposing hematological disease. Initial radiographs revealed a bony lesion arising posteriorly from the C2-3 laminae and spinous processes. Subsequent imaging suggested the diagnosis, which was confirmed by CT-guided biopsy, peripheral blood smears, and bone marrow aspirate. Despite epidural compression and slight displacement of the cervical cord and thecal sac, the patient's symptoms were limited to pain and diminished cervical range of motion. Therefore, surgery was deferred in favor of nonsurgical therapy. Several alternative modalities for the treatment of EMH have been suggested in the literature, including cytotoxic agents and radiotherapy. The authors opted for an approach utilizing directed low-dose radiotherapy of a total of 25 Gy divided in 2.5-Gy fractions. At the 3-month follow-up, the patient continued to be asymptomatic, and MRI demonstrated a significant reduction in the dimensions of the lesion. Extramedullary hematopoiesis with spinal cord compression in the absence of a preexisting hematological disorder has not been described in

  1. CompTIA Network+ Review Guide (Exam N10-004)

    CERN Document Server

    Ferguson, Bill

    2009-01-01

    Serving as a concise, focused study aid to help you prepare for the leading non-vendor-specific networking certification exam, this book features more review questions and study review features than any other guide, with over 120 review questions, two bonus exams, and electronic Flashcard, as well as a searchable Glossary of Terms database on CD-ROM. Fully updated for the first revision of the CompTIA Network+ exam since 2005, the book is organized by exam objectives and broken into six parts corresponding to the six domain areas of the Network+ exam: technologies, media and topologies, device

  2. Paraplegia due to extramedullary hematopoiesis in thalassemia treated successfully with radiation therapy.

    Science.gov (United States)

    Malik, Monica; Pillai, Lakshmi S; Gogia, Nidhi; Puri, Tarun; Mahapatra, M; Sharma, Daya Nand; Kumar, Rajat

    2007-03-01

    Spinal cord compression due to extramedullary hematopoiesis (EMH) is a rare complication of thalassemia and generally presents as paraparesis with sensory impairment. Complete paraplegia is extremely rare in EMH due to thalassemia although it is known to occur in polycythemia vera and sickle cell anemia. Treatment options mostly include surgery and/or radiotherapy. Whereas cases presenting with paraparesis have been treated with either surgery or radiotherapy with equal frequency and efficacy, almost all reported cases with paraplegia have been treated with surgery with or without radiation therapy. We hereby report a case of thalassemia intermedia with paraplegia treated successfully with radiotherapy.

  3. Protective effects of bacterial endotoxin in reconstruction of hematopoiesis after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Wenzhong, Zhao; Renqian, Zhong [Second Military medical Coll., Shanghai, SH (China). Dept. of Radiation Medicine

    1989-06-01

    The mechanism of protective effects of bacterial endotoxin (ET) in reconstruction of hemopoiesis post-irradiation has been studied. The results showed that (1) in normal men, dogs, rabbits and rats, after im injection of typhobacterial endotoxin (ETt), the peripheral blood leucocytes (PBL) increased in number remarkably; (2) the injection of microdoses of ETt into hypothalamus of the rabbits and rats caused no obvious change in number of PBL, suggesting that there was neither regulation on the granulomacrophagopoiesis of the vegetative nervous center in hypothalamus nor the regulative effect of the hypothalamo-pituitary endocrine system. The curves of the stimulating factor (CSF) levels in serum after injection of bacillus coli endotoxin (ETc) were compared between the mouse bone marrow cell (BMC) membrane {sup 3}H-galactose incorporation method and the agar cellular colony culture technique. It was shown that they had obvious relationships with the dose-response curve of purified CSF-1. There was no effect on the incorporation value and colony number when ETc was added to culture well directly. The protective effects of the ETc-serum on the 8 Gy irradiated mice was realized by inducing GM-CSF and promoting the reconstruction of hematopoiesis.

  4. Functional analysis of the interdependence between DNA uptake sequence and its cognate ComP receptor during natural transformation in Neisseria species.

    Directory of Open Access Journals (Sweden)

    Jamie-Lee Berry

    Full Text Available Natural transformation is the widespread biological process by which "competent" bacteria take up free DNA, incorporate it into their genomes, and become genetically altered or "transformed". To curb often deleterious transformation by foreign DNA, several competent species preferentially take up their own DNA that contains specific DUS (DNA uptake sequence watermarks. Our recent finding that ComP is the long sought DUS receptor in Neisseria species paves the way for the functional analysis of the DUS-ComP interdependence which is reported here. By abolishing/modulating ComP levels in Neisseria meningitidis, we show that the enhancement of transformation seen in the presence of DUS is entirely dependent on ComP, which also controls transformation in the absence of DUS. While peripheral bases in the DUS were found to be less important, inner bases are essential since single base mutations led to dramatically impaired interaction with ComP and transformation. Strikingly, naturally occurring DUS variants in the genomes of human Neisseria commensals differing from DUS by only one or two bases were found to be similarly impaired for transformation of N. meningitidis. By showing that ComPsub from the N. subflava commensal specifically binds its cognate DUS variant and mediates DUS-enhanced transformation when expressed in a comP mutant of N. meningitidis, we confirm that a similar mechanism is used by all Neisseria species to promote transformation by their own, or closely related DNA. Together, these findings shed new light on the molecular events involved in the earliest step in natural transformation, and reveal an elegant mechanism for modulating horizontal gene transfer between competent species sharing the same niche.

  5. Minocycline treatment attenuates non-Ang II[125I] CGP42112 binding in brainstem following nodose ganglionectomy

    International Nuclear Information System (INIS)

    Roulston, C.L.; Widdop, R.E.; Jarrott, B.

    2001-01-01

    Full text: Non-Ang II [ 125 I]CGP42112 binding was revealed in rat dorsal motor nucleus (DMX), ambiguus nucleus (n.amb), and nucleus of the solitary tract (NTS), following unilateral nodose ganglionectomy (NGX). This upregulated binding may be due to activated microglia. Given that tetracyclines inhibit microglia activation, we examined the effect of minocycline treatment on [ 125 I]CGP42112 and [ 3 H] PK11195 binding (a know marker for activated microglia), following NGX using autoradiography. Male Wistar Kyoto (WKY)rats underwent NGX or sham operation (mexohexitione anaesthesia, 60mg/kg ip). Animals were given saline or minocycline (50 mg/kg ip)12 hours before surgery and twice daily after NGX (each 100mg/kg ip)for 3 days. Slide-mounted brainstem sections (14 μm) were prepared and incubated in the presence of either [ 125 I]CGP42112 (0.3nM) or [ 3 H]PK11195 (3nM) and apposed to film for 10 days. Specific binding was determined in adjacent sections co- incubated with unlabelled displacers. Non-Ang II [ 125 I]CGP42112 binding in DMX and n.amb was revealed on the denervated side in saline-treated rats (n=4), whereas this effect was reduced by ∼41 % and ∼ 54%, respectively, in minocycline-treated rats (n=4). Analogous experiments using [ 3 H] PK11195 showed upregulated binding on the denervated side in DMX (44 ± 4 %) and in n.amb (68 ± 3 %) of saline-treated rats (n=4), which was reduced by ∼ 45% with minocyline treatment in both nuclei (n=4). Minocycline also attenuated NGX-induced upregulated binding to both ligands in the NTS. Thus, these data suggest that non-Ang II[ 125 I]CGP42112 binds to activated microglia, indicated by reduced binding densities following treatment with minocycline. Copyright (2001) Australian Neuroscience Society

  6. Efectos hipotalámicos de la angiotensina-[1-7] en ratas con coartación aórtica

    Directory of Open Access Journals (Sweden)

    Clara Peña

    2005-01-01

    Full Text Available Hypothalamic Effects of Angiotensin (1-7 in Rats with Aortic Coarctation Christian Höcht, Javier A. W. Opezzo, Mariela Gironacci, Clara Peña, Carlos A. Taira The objective of the present study was to evaluate the effect of the intrahypothalamic administration of angiotensin-[1-7] (Ang-[1-7] on blood pressure and heart rate and on angiotensin II (Ang-II activity in rats with sham operation (SO and rats with aortic coarctation (ACo in early and chronic stage of hypertension. Wistar rats were used. Seven and 42 days after the corresponding operation one carotid artery was cannulated for the measurement of the mean arterial pressure (MAP in anaesthetized rats and an injection needle was inserted in the anterior hypothalamus by means of a stereotactic frame for the administration of Ang-II (50 ng, Ang-[1-7] (50 ng and Ang-II + Ang-[1-7] (50 + 50 ng. Hypothalamic administration of Ang-II produced an increased MAP in the ACo rats when compared to the control group in the early and chronic stages of hypertension, whereas Ang-[1-7] did not induce significant changes in any experimental group. The co-administration of Ang -[1-7] reduced the pressure activity of the Ang-II in both early and chronic stages of hypertension in the ACo rats, whereas it had no effect on the pressure activity of Ang-II in the normotensive rats. In conclusion, the pressure activity of Ang-II is increased in rats with early and chronic stages of arterial hypertension. The antagonistic effect of Ang-[1-7] may indicate that this peptide could modulate the pressure activity of an already increased Ang-II, since it has been only observed in the hypertensive rats.

  7. The protumorigenic potential of FTY720 by promoting extramedullary hematopoiesis and MDSC accumulation.

    Science.gov (United States)

    Li, Y; Zhou, T; Wang, Y; Ning, C; Lv, Z; Han, G; Morris, J C; Taylor, E N; Wang, R; Xiao, H; Hou, C; Ma, Y; Shen, B; Feng, J; Guo, R; Li, Y; Chen, G

    2017-06-29

    FTY720 (also called fingolimod) is recognized as an immunosuppressant and has been approved by the Food and Drug Administration to treat refractory multiple sclerosis. However, long-term administration of FTY720 potentially increases the risk for cancer in recipients. The underlying mechanisms remain poorly understood. Herein, we provided evidence that FTY720 administration potentiated tumor growth. Mechanistically, FTY720 enhanced extramedullary hematopoiesis and massive accumulation of myeloid-derived suppressor cells (MDSCs), which actively suppressed antitumor immune responses. Granulocyte-macrophage colony-stimulating factor (GM-CSF), mainly produced by MDSCs, was identified as a key factor to mediate these effects of FTY720 in tumor microenvironment. Furthermore, we showed that FTY720 triggers MDSCs to release GM-CSF via S1P receptor 3 (S1pr3) through Rho kinase and extracellular signal-regulated kinase-dependent pathway. Thus, our findings provide mechanistic explanation for the protumorigenic potentials of FTY720 and suggest that targeting S1pr3 simultaneously may be beneficial for the patients receiving FTY720 treatment.

  8. A phase I/II trial of beta-(1,3/(1,6 D-glucan in the treatment of patients with advanced malignancies receiving chemotherapy

    Directory of Open Access Journals (Sweden)

    Weitberg Alan B

    2008-09-01

    Full Text Available Abstract β-(1,3/(1,6 D-glucan, a component of the fungal cell wall, has been shown to stimulate the immune system, enhance hematopoiesis, amplify killing of opsonized tumor cells and increase neutrophil chemotaxis and adhesion. In view of these attributes, the β-glucans should be studied for both their therapeutic efficacy in patients with cancer as well as an adjunctive therapy in patients receiving chemotherapy as a maneuver to limit suppression of hematopoiesis. In this study, twenty patients with advanced malignancies receiving chemotherapy were given a β-(1,3/(1,6 D-glucan preparation (MacroForce plus IP6, ImmuDyne, Inc. and monitored for tolerability and effect on hematopoiesis. Our results lead us to conclude that β-glucan is well-tolerated in cancer patients receiving chemotherapy, may have a beneficial effect on hematopoiesis in these patients and should be studied further, especially in patients with chronic lymphocytic leukemia and lymphoma.

  9. Cross talk between MMP2-Spm-Cer-S1P and ERK1/2 in proliferation of pulmonary artery smooth muscle cells under angiotensin II stimulation.

    Science.gov (United States)

    Chowdhury, Animesh; Sarkar, Jaganmay; Pramanik, Pijush Kanti; Chakraborti, Tapati; Chakraborti, Sajal

    2016-08-01

    The aim of the present study is to establish the mechanism associated with the proliferation of PASMCs under ANG II stimulation. The results showed that treatment of PASMCs with ANG II induces an increase in cell proliferation and 100 nM was the optimum concentration for maximum increase in proliferation of the cells. Pretreatment of the cells with AT1, but not AT2, receptor antagonist inhibited ANG II induced cell proliferation. Pretreatment with pharmacological and genetic inhibitors of sphingomyelinase (SMase) and sphingosine kinase (SPHK) prevented ANG II-induced cell proliferation. ANG II has also been shown to induce SMase activity, SPHK phosphorylation and S1P production. In addition, ANG II caused an increase in proMMP-2 expression and activation, ERK1/2 phosphorylation and NADPH oxidase activation. Upon inhibition of MMP-2, SMase activity and S1P level were curbed leading to inhibition of cell proliferation. SPHK was phosphorylated by ERK1/2 during ET-1 stimulation of the cells. ANG II-induced ERK1/2 phosphorylation and proMMP-2 expression and activation in the cells were abrogated upon inhibition of NADPH oxidase activity. Overall, NADPH oxidase plays an important role in proMMP-2 expression and activation and that MMP-2 mediated SMC proliferation occurs through the involvement of Spm-Cer-S1P signaling axis under ANG II stimulation of PASMCs. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. La compétence interculturelle et la formation initiale : le point sur le CECR et l’IDI

    Directory of Open Access Journals (Sweden)

    Karen Olivia Ragoonaden

    2011-12-01

    Full Text Available Abstract Ce projet pilote traite principalement de la compétence interculturelle des étudiants en formation initiale du français langue seconde. Douze étudiants ont répondu au questionnaire de l’IDI (inventaire de développement interculturel, un outil méthodologique qui mesure les orientations concernant la différence culturelle. Les profils interculturels, calculés d’après les résultats de l’IDI, servent de toile de fond pour proposer la mise en œuvre des interventions interculturelles selon les paramètres établis par les compétences générales du Cadre européen commun de référence pour les langues (CECR. Les travaux menés pourraient contribuer à l’élaboration des cours/ateliers en compétence interculturelle, à l’intégration des savoirs socioculturels et à la prise de conscience interculturelle identifiés dans les compétences générales du Cadre européen commun de référence pour les langues dans les cours de formation initiale. Resume This pilot study focuses on the intercultural competence of preservice French as a second language (FSL teachers. The Intercultural Development Index (IDI, a statistically valid tool used to measure intercultural competence, was administered to twelve preservice candidates. These results serve as a basis to discuss the integration of intercultural competencies along the parameters established in the general competencies of the CEFR. This study has the potential to contribute to a growing area of research in the field of intercultural competence in preservice teacher education and explores how sociocultural saviors and intercultural awareness, identified by the Common European Framework of Reference for Languages, can be integrated into Teacher Education.

  11. Blood morphology and the levels of selected cytokines related to hematopoiesis in occupational short-term exposure to lead

    International Nuclear Information System (INIS)

    Dobrakowski, Michał; Boroń, Marta; Czuba, Zenon P.; Birkner, Ewa; Chwalba, Artur; Hudziec, Edyta; Kasperczyk, Sławomir

    2016-01-01

    The aim of the study was to investigate the influence of a short-term exposure to lead on the blood morphology and the levels of selected cytokines related to hematopoiesis in occupationally exposed workers. The study population included 37 males occupationally exposed to lead for 36 to 44 days. Their blood lead level raised from 10.7 ± 7.67 μg/dl at baseline to the level of 49.1 ± 14.1 μg/dl at the end of the study. The level of hemoglobin and values of MCH and MCHC were decreased due to a short-term exposure to lead by 2%, 2%, and 1%, respectively. The counts of WBC, LYM, and MXD increased significantly by 5%, 7%, and 35%. Similarly, the count of PLT increased by 7%, while PDW, MPV, and P-LCR decreased by 6%, 3%, and 9%, respectively. The levels of IL-7, G-CSF, HGF, PDGF AB/BB, SCF, and PECAM-1, decreased significantly by 30%, 33%, 8%, 30%, 25%, and 20%, respectively. A short-term occupational exposure to lead results in a decreased hemoglobin level and increased counts of WBC and PLT. Changes in counts and proportions of different types of leukocytes and decreased values of PLT indices, such as PDW, MPV, and P-LCR, due to the subacute lead-exposure may be associated with lead-induced decreased levels of cytokines related to hematopoiesis, including SCF, G-CSF, IL-7, and PDGF. - Highlights: • Subacute exposure to lead results in a decreased hemoglobin level. • Subacute exposure to lead results in increased counts of WBC and PLT. • Subacute exposure to lead decreases the levels of SCF, G-CSF, IL-7, and PDGF.

  12. Blood morphology and the levels of selected cytokines related to hematopoiesis in occupational short-term exposure to lead

    Energy Technology Data Exchange (ETDEWEB)

    Dobrakowski, Michał, E-mail: michal.dobrakowski@poczta.fm [Department of Biochemistry, School of Medicine with the Division of Dentistry, Medical University of Silesia, ul. Jordana 19, 41-808 Zabrze (Poland); Boroń, Marta [Institute of Occupational Medicine and Environmental Health in Sosnowiec, ul. Kościelna 13, 41-200 Sosnowiec (Poland); Czuba, Zenon P. [Department of Microbiology and Immunology, School of Medicine with the Division of Dentistry, Medical University of Silesia, ul. Jordana 19, 41-808 Zabrze (Poland); Birkner, Ewa [Department of Biochemistry, School of Medicine with the Division of Dentistry, Medical University of Silesia, ul. Jordana 19, 41-808 Zabrze (Poland); Chwalba, Artur [SP ZOZ Municipal Hospital, Department of Internal Medicine, ul. Strzelców Bytomskich 11, 41-500 Chorzów (Poland); Hudziec, Edyta; Kasperczyk, Sławomir [Department of Biochemistry, School of Medicine with the Division of Dentistry, Medical University of Silesia, ul. Jordana 19, 41-808 Zabrze (Poland)

    2016-08-15

    The aim of the study was to investigate the influence of a short-term exposure to lead on the blood morphology and the levels of selected cytokines related to hematopoiesis in occupationally exposed workers. The study population included 37 males occupationally exposed to lead for 36 to 44 days. Their blood lead level raised from 10.7 ± 7.67 μg/dl at baseline to the level of 49.1 ± 14.1 μg/dl at the end of the study. The level of hemoglobin and values of MCH and MCHC were decreased due to a short-term exposure to lead by 2%, 2%, and 1%, respectively. The counts of WBC, LYM, and MXD increased significantly by 5%, 7%, and 35%. Similarly, the count of PLT increased by 7%, while PDW, MPV, and P-LCR decreased by 6%, 3%, and 9%, respectively. The levels of IL-7, G-CSF, HGF, PDGF AB/BB, SCF, and PECAM-1, decreased significantly by 30%, 33%, 8%, 30%, 25%, and 20%, respectively. A short-term occupational exposure to lead results in a decreased hemoglobin level and increased counts of WBC and PLT. Changes in counts and proportions of different types of leukocytes and decreased values of PLT indices, such as PDW, MPV, and P-LCR, due to the subacute lead-exposure may be associated with lead-induced decreased levels of cytokines related to hematopoiesis, including SCF, G-CSF, IL-7, and PDGF. - Highlights: • Subacute exposure to lead results in a decreased hemoglobin level. • Subacute exposure to lead results in increased counts of WBC and PLT. • Subacute exposure to lead decreases the levels of SCF, G-CSF, IL-7, and PDGF.

  13. Angiotensin II increases CTGF expression via MAPKs/TGF-{beta}1/TRAF6 pathway in atrial fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Jun [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of medicine, Shanghai (China); Liu, Xu, E-mail: xkliuxu@yahoo.cn [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of medicine, Shanghai (China); Wang, Quan-xing, E-mail: shmywqx@126.com [National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai (China); Tan, Hong-wei [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of medicine, Shanghai (China); Guo, Meng [National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai (China); Jiang, Wei-feng; Zhou, Li [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of medicine, Shanghai (China)

    2012-10-01

    The activation of transforming growth factor-{beta}1(TGF-{beta}1)/Smad signaling pathway and increased expression of connective tissue growth factor (CTGF) induced by angiotensin II (AngII) have been proposed as a mechanism for atrial fibrosis. However, whether TGF{beta}1/non-Smad signaling pathways involved in AngII-induced fibrogenetic factor expression remained unknown. Recently tumor necrosis factor receptor associated factor 6 (TRAF6)/TGF{beta}-associated kinase 1 (TAK1) has been shown to be crucial for the activation of TGF-{beta}1/non-Smad signaling pathways. In the present study, we explored the role of TGF-{beta}1/TRAF6 pathway in AngII-induced CTGF expression in cultured adult atrial fibroblasts. AngII (1 {mu}M) provoked the activation of P38 mitogen activated protein kinase (P38 MAPK), extracellular signal-regulated kinase 1/2(ERK1/2) and c-Jun NH(2)-terminal kinase (JNK). AngII (1 {mu}M) also promoted TGF{beta}1, TRAF6, CTGF expression and TAK1 phosphorylation, which were suppressed by angiotensin type I receptor antagonist (Losartan) as well as p38 MAPK inhibitor (SB202190), ERK1/2 inhibitor (PD98059) and JNK inhibitor (SP600125). Meanwhile, both TGF{beta}1 antibody and TRAF6 siRNA decreased the stimulatory effect of AngII on TRAF6, CTGF expression and TAK1 phosphorylation, which also attenuated AngII-induced atrial fibroblasts proliferation. In summary, the MAPKs/TGF{beta}1/TRAF6 pathway is an important signaling pathway in AngII-induced CTGF expression, and inhibition of TRAF6 may therefore represent a new target for reversing Ang II-induced atrial fibrosis. -- Highlights: Black-Right-Pointing-Pointer MAPKs/TGF{beta}1/TRAF6 participates in AngII-induced CTGF expression in atrial fibroblasts. Black-Right-Pointing-Pointer TGF{beta}1/TRAF6 participates in AngII-induced atrial fibroblasts proliferation. Black-Right-Pointing-Pointer TRAF6 may represent a new target for reversing Ang II-induced atrial fibrosis.

  14. De la terre à la table : renforcer les compétences des agriculteurs ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    De la terre à la table : renforcer les compétences des agriculteurs urbains en organisation et en mise en marché (Moyen-Orient et Afrique du Nord). Le réseau ... Stichting International Network of Resource Centres on Urban Agriculture and Food Security. Pays d' institution. Pays-Bas. Site internet. http://www.ruaf.org ...

  15. CompTIA Network+ Certification Study Guide, Exam N10-004

    CERN Document Server

    Shimonski, Robert

    2009-01-01

    CompTIA's Network+ certification is a globally-recognized, vendor neutral exam that has helped over 235,000 IT professionals reach further and higher in their careers. The 2009 Network+ exam (N10-004) is a major update with more focus on security and wireless aspects of networking. Our new study guide has been updated accordingly with focus on network, systems, and WAN security and complete coverage of today's wireless networking standards. As always this companion covers the core Network+ material including basic design principles, management and operation of a network infrastructure, and tes

  16. Predominance of AT1 Blockade Over Mas–Mediated Angiotensin-(1–7) Mechanisms in the Regulation of Blood Pressure and Renin–Angiotensin System in mRen2.Lewis Rats

    Science.gov (United States)

    2013-01-01

    BACKGROUND We investigated whether the antihypertensive actions of the angiotensin II (Ang II) receptor (AT1-R) blocker, olmesartan medoxomil, may in part be mediated by increased Ang-(1–7) in the absence of significant changes in plasma Ang II. METHODS mRen2.Lewis congenic hypertensive rats were administered either a vehicle (n = 14) or olmesartan (0.5mg/kg/day; n = 14) by osmotic minipumps. Two weeks later, rats from both groups were further randomized to receive either the mas receptor antagonist A-779 (0.5mg/kg/day; n = 7 per group) or its vehicle (n = 7 per group) for the next 4 weeks. Blood pressure was monitored by telemetry, and circulating and tissue components of the renin–angiotensin system (RAS) were measured at the completion of the experiments. RESULTS Antihypertensive effects of olmesartan were associated with an increase in plasma renin concentration, plasma Ang I, Ang II, and Ang-(1–7), whereas serum aldosterone levels and kidney Ang II content were reduced. Preserved Ang-(1–7) content in kidneys was associated with increases of ACE2 protein but not activity and no changes on serum and kidney ACE activity. There was no change in cardiac peptide levels after olmesartan treatment. The antihypertensive effects of olmesartan were not altered by concomitant administration of the Ang-(1–7) receptor antagonist except for a mild further increase in plasma renin concentration. CONCLUSIONS Our study highlights the independent regulation of RAS among plasma, heart, and kidney tissue in response to AT1-R blockade. Ang-(1–7) through the mas receptor does not mediate long-term effects of olmesartan besides counterbalancing renin release in response to AT1-R blockade. PMID:23459599

  17. Angiotensin (1-7) ameliorates the structural and biochemical alterations of ovariectomy-induced osteoporosis in rats via activation of ACE-2/Mas receptor axis.

    Science.gov (United States)

    Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

    2017-05-23

    The local and systemic renin angiotensin system (RAS) influences the skeletal system micro-structure and metabolism. Studies suggested angiotensin 1-7 (Ang(1-7)) as the beneficial RAS molecule via Mas receptor activation. This study examines the function of Ang(1-7) in bone micro-architecture and metabolism in an ovariectomized (OVX) rodent model of osteoporosis. OVX rats showed structural and bone metabolic degeneration in parallel with suppressed expressions of the angiotensin converting enzyme-2 (ACE-2)/Ang(1-7)/Mas components. The infusion of Ang(1-7) markedly alleviated the altered bone metabolism and significantly enhanced both trabecular (metaphyseal) and cortical (metaphyseal-diaphyseal) morphometry. Urinary and bones minerals were also improved in OVX rats by Ang(1-7). The infusion of the heptapeptide enhanced ACE-2/Mas receptor expressions, while down-regulated AngII, ACE, and AngII type-1 receptor (AT1R) in OVX animals. Moreover, Ang(1-7) markedly improved osteoprotegerin (OPG) and lowered receptor activator NF-κB ligand (RANKL) expressions. The defensive properties of Ang(1-7) on bone metabolism, structure and minerals were considerably eradicated after blockage of Mas receptor with A-779. Ang(1-7)-induced up-regulated ACE-2/Ang(1-7)/Mas cascade and OPG expressions were abolished and the expressions of ACE/AngII/AT1R and RANKL were provoked by A-779. These findings shows for the first time the novel valuable therapeutic role of Ang(1-7) on bone health and metabolism through the ACE-2/Mas cascade.

  18. The complex of PAMAM-OH dendrimer with Angiotensin (1-7) prevented the disuse-induced skeletal muscle atrophy in mice.

    Science.gov (United States)

    Márquez-Miranda, Valeria; Abrigo, Johanna; Rivera, Juan Carlos; Araya-Durán, Ingrid; Aravena, Javier; Simon, Felipe; Pacheco, Nicolás; González-Nilo, Fernando Danilo; Cabello-Verrugio, Claudio

    2017-01-01

    Angiotensin (1-7) (Ang-(1-7)) is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues - among them, skeletal muscle - by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimer as an Ang-(1-7) carrier. Bioinformatics analysis showed that the Ang-(1-7)-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1-7) and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1-7)/PAMAM-OH complex, but not Ang-(1-7) alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1-7)/PAMAM-OH complex being intraperitoneally injected were similar to the results obtained when Ang-(1-7) was systemically administered through mini-osmotic pumps. Together, the results suggest that Ang-(1-7) can be protected for PAMAM-OH when this complex is intraperitoneally injected. Therefore, the Ang-(1-7)/PAMAM-OH complex is an efficient delivery method for Ang-(1-7), since it improves the anti-atrophic activity of this peptide in skeletal muscle.

  19. Functionally Selective AT(1) Receptor Activation Reduces Ischemia Reperfusion Injury

    DEFF Research Database (Denmark)

    Hostrup, Anders; Christensen, Gitte Lund; Bentzen, Bo Hjort

    2012-01-01

    of the physiological functions of AngII. The AT(1)R mediates its effects through both G protein-dependent and independent signaling, which can be separated by functionally selective agonists. In the present study we investigate the effect of AngII and the ß-arrestin biased agonist [SII]AngII on ischemia......]AngII had a protective effect. Together these results demonstrate a cardioprotective effect of simultaneous blockade of G protein signaling and activation of G protein independent signaling through AT(1 )receptors....

  20. Mechanisms Involving Ang II and MAPK/ERK1/2 Signaling Pathways Underlie Cardiac and Renal Alterations during Chronic Undernutrition

    Science.gov (United States)

    Pereira-Acácio, Amaury; Luzardo, Ricardo; Sampaio, Luzia S.; Luna-Leite, Marcia A.; Lara, Lucienne S.; Einicker-Lamas, Marcelo; Panizzutti, Rogério; Madeira, Caroline; Vieira-Filho, Leucio D.; Castro-Chaves, Carmen; Ribeiro, Valdilene S.; Paixão, Ana D. O.; Medei, Emiliano; Vieyra, Adalberto

    2014-01-01

    Background Several studies have correlated protein restriction associated with other nutritional deficiencies with the development of cardiovascular and renal diseases. The driving hypothesis for this study was that Ang II signaling pathways in the heart and kidney are affected by chronic protein, mineral and vitamin restriction. Methodology/Principal Findings Wistar rats aged 90 days were fed from weaning with either a control or a deficient diet that mimics those used in impoverished regions worldwide. Such restriction simultaneously increased ouabain-insensitive Na+-ATPase and decreased (Na++K+)ATPase activity in the same proportion in cardiomyocytes and proximal tubule cells. Type 1 angiotensin II receptor (AT1R) was downregulated by that restriction in both organs, whereas AT2R decreased only in the kidney. The PKC/PKA ratio increased in both tissues and returned to normal values in rats receiving Losartan daily from weaning. Inhibition of the MAPK pathway restored Na+-ATPase activity in both organs. The undernourished rats presented expanded plasma volume, increased heart rate, cardiac hypertrophy, and elevated systolic pressure, which also returned to control levels with Losartan. Such restriction led to electrical cardiac remodeling represented by prolonged ventricular repolarization parameters, induced triggered activity, early after-depolarization and delayed after-depolarization, which were also prevented by Losartan. Conclusion/Significance The mechanisms responsible for these alterations are underpinned by an imbalance in the PKC- and PKA-mediated pathways, with participation of angiotensin receptors and by activation of the MAPK/ERK1/2 pathway. These cellular and molecular alterations culminate in cardiac electric remodeling and in the onset of hypertension in adulthood. PMID:24983243

  1. Extramedullary pulmonary hematopoiesis causing pulmonary hypertension and severe tricuspid regurgitation detected by 99m technetium sulfur colloid bone marrow scan and single-photon emission computed tomography/CT

    International Nuclear Information System (INIS)

    Ali, Syed Zama; Clarke, Michael John; Kannivelu, Anbalagan; Chinchure, Dinesh; Srinivasan, Sivasubramanian

    2014-01-01

    Extramedullary pulmonary hematopoiesis is a rare entity with a limited number of case reports in the available literature only. We report the case of a 66-year-old man with known primary myelofibrosis, in whom a 99m technetium sulfur colloid bone marrow scan with single-photon emission computed tomography (SPECT)/CT revealed a pulmonary hematopoiesis as the cause of pulmonary hypertension and severe tricuspid regurgitation. To the best of our knowledge, this is the first description of 99m technetium sulfur colloid SPECT/CT imaging in this rare condition.

  2. Correlation between plasma angiopoietin-1, angiopoietin-2 and matrix metalloproteinase-2 in coronary heart disease.

    Science.gov (United States)

    Wu, Haoyu; Shou, Xiling; Liang, Lei; Wang, Congxia; Yao, Xiaowei; Cheng, Gong

    2016-12-01

    Angiopoietin-2 (Ang-2) plays a critical role in inducing tumor cell infiltration, and this invasive phenotype is caused by up-regulation of matrix metalloproteinase (MMP)-2. The relationship between Ang-2 and MMP-2 in atherosclerosis has not been reported yet. The aim is to measure the plasma concentrations of Ang-1, Ang-2 and MMP-2 and assess the correlation between the concentrations of these factors in coronary heart disease (CHD) patients. The testing was done in a cross-sectional study. We prospectively enrolled 42 individuals with acute myocardial infarction, 42 individuals with unstable angina pectoris, 42 individuals with stable angina pectoris and 45 healthy control subjects. Concentrations of Ang-1, Ang-2 and MMP-2 were measured using the enzyme-linked immunosorbent assay (ELISA) method. Spearman's rank correlation was calculated to evaluate the relationships between MMP-2 and Ang-1, and MMP-2 and Ang-2 in patients with CHD. Patients with acute myocardial infarction and unstable angina pectoris had higher Ang-2 and MMP-2 levels compared with stable angina patients and healthy control subjects ( p correlation showed that Ang-2 levels positively correlated with MMP-2 in patients with CHD ( r = 0.679, p correlated weakly with MMP-2, whereas the Ang-2 and MMP-2 correlation was strong in patients with CHD. Ang-2 may play a role in atherosclerosis, and have an interaction with MMP-2.

  3. Incomplete paraplegia caused by extramedullary hematopoiesis in a patient with thalassemia intermedia.

    Science.gov (United States)

    Hisamud-Din, Nurhasyimah; Mustafah, Nadia Mohd; Fauzi, Aishah Ahmad; Hashim, Natiara Mohamad

    2017-01-01

    Extramedullary hematopoiesis (EMH) is the production of blood cell precursors outside the bone marrow that occur in various hematological diseases. In patients with thalassemia intermedia, ineffective erythropoiesis drives compensatory EMH in the liver, pancreas, pleura, spleen, ribs and spine. We describe a patient with thalassemia intermedia who presented with acute neurological symptoms caused by paraspinal EMH, which responded well to combination therapy of steroid, hypertransfusion, laminectomy and excision of pseudotumor and hydroxyurea therapy to boost the formation of fetal haemoglobin. Prompt recognition of EMH based on clinical presentation and typical radiological findings should be made. Early treatment is recommended to prevent irreversible damage to the spinal cord.

  4. Adrenomedullin and angiopoietin-1 additively restore erectile function in diabetic rats: comparison with the combination therapy of vascular endothelial growth factor and angiopoietin-1.

    Science.gov (United States)

    Nishimatsu, Hiroaki; Suzuki, Etsu; Nomiya, Akira; Niimi, Aya; Suzuki, Motofumi; Fujimura, Tetsuya; Fukuhara, Hiroshi; Homma, Yukio

    2013-07-01

    Erectile dysfunction (ED) is a major health problem. We have shown that adrenomedullin (AM) restores erectile function in diabetic rats. The aim of this study is to explore a better treatment for ED, we examined whether combination of AM and angiopoietin-1 (Ang-1) was more effective to treat ED than treatment with AM alone or Ang-1 alone. We also compared the effect of the combination therapy with that of treatment with vascular endothelial growth factor-A (VEGF-A). Male Wistar rats were injected with streptozotocin (STZ) to induce diabetes. Adenoviruses expressing AM (AdAM), Ang-1 (AdAng-1), and VEGF-A (AdVEGF-A) were injected into the penis 6 weeks after STZ administration. Erectile function, penile histology, and protein expression were analyzed 4 weeks after the injection of the adenoviruses. Intracavernous pressure and mean arterial pressure were measured to evaluate erectile function. The morphology of the penis was analyzed by Elastica van Gieson stain and immunohistochemistry. The expression of α-smooth muscle actin (SMA), VE-cadherin and type I collagen was assessed by Western blot analysis. Infection with AdAM plus AdAng-1 more effectively restored erectile function than infection with AdAM alone or AdAng-1 alone. This combination therapy restored erectile function to a level similar to that observed in the age-matched Wistar rats. Expression of SMA and VE-cadherin increased more significantly in the AdAM plus AdAng-1-treated group than in the AdAM- or AdAng-1-treated group. Although AdVEGF-A infection restored erectile function significantly, it also caused enlargement of the trabeculae of the cavernous body, aberrant angiogenesis, and overproduction of type I collagen. These results suggested that combination therapy with AM and Ang-1 potently restored erectile function and normal morphology of the cavernous body compared with VEGF-A administration. This combination therapy will be useful to treat ED patients with a severely damaged cavernous body.

  5. Angiotensin-(1-7): A Novel Peptide to Treat Hypertension and Nephropathy in Diabetes?

    Science.gov (United States)

    Padda, Ranjit Singh; Shi, Yixuan; Lo, Chao-Sheng; Zhang, Shao-Ling; Chan, John S D

    2015-10-14

    The renin-angiotensin system (RAS) plays a pivotal role in mammalian homeostasis physiology. The RAS can be delineated into a classical RAS (the pressor arm) including angiotensinogen (Agt), renin, angiotensin-converting enzyme (ACE), angiotensin II (Ang II) and angiotensin type 1 receptor (AT1R), and a counterbalancing novel RAS (the depressor arm) including Agt, renin, angiotensin-converting enzyme-2 (ACE-2), angiotensin-(1-7) (Ang 1-7) and Ang 1-7 receptor (or Mas receptor (MasR)). Hyperglycemia (diabetes) induces severe tissue oxidative stress, which stimulates the pressor arm of the renal RAS axis and leads to an increase in ACE/ACE-2 ratio, with excessive formation of Ang II. There is a growing body of evidence for beneficial effects of the depressor arm of RAS (ACE-2/Ang 1-7/MasR) axis in diabetes, hypertension and several other diseased conditions. Evidence from in vitro, in vivo and clinical studies reflects anti-oxidant, anti-fibrotic, and anti-inflammatory properties of Ang 1-7. Most of the currently available therapies only target suppression of the pressor arm of RAS with angiotensin receptor blockers (ARBs) and ACE inhibitors (ACEi). However, it is time to consider simultaneous activation of the depressor arm for more effective outcomes. This review summarizes the recent updates on the protective role of Ang 1-7 in hypertension and kidney injury in diabetes, as well as the possible underlying mechanism(s) of Ang 1-7 action, suggesting that the ACE-2/Ang 1-7/MasR axis can be developed as a therapeutic target for the treatment of diabetes-induced hypertension and renal damage.

  6. Compósitos de Borracha Natural com Compostos Condutivos à Base de Negro de Fumo e Polímero Condutor Natural Rubber Composites with Conductive Compounds based on Carbon Black and Conducting Polymers

    Directory of Open Access Journals (Sweden)

    Marinalva A. dos Santos

    2001-09-01

    Full Text Available Neste trabalho foram desenvolvidos compósitos condutores elétricos de borracha natural contendo negro de fumo e compostos condutivos baseados em polímeros condutores (Eenomer®. Os compósitos foram processados a quente num reômetro de torque HAAKE e moldados por prensagem. Foram obtidas placas homogêneas, flexíveis e com ótimo acabamento superficial. Os compósitos foram analisados pelas medidas de torque no processamento, medidas de condutividade elétrica, análise termogravimétrica (TGA, calorimetria diferencial de varredura (DSC e ensaios de tração. Estes compósitos apresentaram valores de condutividade elétrica entre 10-7 a 10-1 S/cm, dependendo do tipo de negro de fumo ou composto condutivo utilizado e da quantidade destes no compósito. A análise térmica demonstrou que os compósitos são termicamente estáveis até cerca de 300°C. Os compostos condutivos atuam como reforço para a borracha natural melhorando suas propriedades mecânicas sem perder significativamente sua flexibilidade.In this work, electrically conducting composites of natural rubber with carbon black and natural rubber with conductive compounds containing electrically conducting polymers (Eenomer® were developed. The composites were processed in a torque reometer HAAKE and then hot pressed. Homogeneous and flexible plates were obtained with excellent surface finish. The composites were analysed by the torque measurement during processing, electrical conductivity, thermogravimetric analysis (TGA, differential scanning calorimetric (DSC and mechanical analysis. Conductivity in the order of 10-7 to 10-1 S/cm were achieved, depending on the type of carbon black or conductive compound used and their content in the composite. Thermal analysis demonstrated that the compounds are thermally stable until 300°C. The conductive compounds act as reinforcements in the natural rubber matrix, improving its mechanical properties without significant loss on its

  7. Ārpus klases aktivitātes pamatskolas skolēnu angļu valodas vārdu krājuma bagātināšanai

    OpenAIRE

    Kalniņa, Maija

    2012-01-01

    Diplomdarba autore četru pedagoģiskā darba gadu laikā ir secinājusi, cik svarīgi ir plānot stundas ne tikai interesantas un interaktīvas, bet arī praktiskas un pēc iespējas tuvākas reālajai dzīvei. Diplomdarba mērķis ir noskaidrot, kā ārpusklases nodarbības var uzlabot skolēnu angļu valodas vārdu krājumu pamatskolā. Šāda diplomdarba tēma tika izvēlēta tādēļ, ka vārdu krājuma bagātināšanai ir liela nozīme angļu valodas apguvē, kā arī, lai skolēni spētu veiksmīgi izmantot angļu valodu,...

  8. Elevated Angiopoietin-1 Serum Levels in Patients with Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Brigitte Schreitmüller

    2012-01-01

    Full Text Available Background. Alzheimer's disease (AD is the most common cause of dementia in the elderly. AD is characterized by the accumulation of amyloid plaques and neurofibrillary tangles and by massive neuronal loss in the brain. There is epidemiologic and pathologic evidence that AD is associated with vascular risk factors and vascular diseases, contributing to cerebral hypoperfusion with consecutive stimulation of angiogenesis and upregulation of proangiogenic factors such as Angiopoietin-1 (Ang-1. Methods. In the present study, we measured Ang-1 serum levels in 42 patients with AD, 20 patients with mild cognitive impairment (MCI, and in 40 healthy elderly controls by ELISA. Results. We found significantly increased Ang-1 serum levels in patients with AD compared to control subjects (P=0.003. There was no significant difference between MCI patients and healthy controls (P=0.553 or between AD and MCI patients (P=0.054. The degree of cognitive impairment as measured by the mini-mental status examination (MMSE score was significantly correlated with the Ang-1 serum levels in all patients and healthy controls. Conclusions. We found significantly increased Ang-1 serum levels in AD patients. We could also show an association between Ang-1 serum levels and the cognitive status in all patients and healthy controls. Thus, serum Ang-1 could be a potential candidate for a biomarker panel for AD diagnosis.

  9. Mācību modeļa "WebQuest"izmantošana angļu valodas apguvē

    OpenAIRE

    Jēgermane, Ilze

    2011-01-01

    Mācību modelis WebQuest ir inovatīva metode mācību procesā, kuru sākotnēji izveidoja un izstrādāja mācību tehnoloģiju profesors Bērnijs Dodžs (Bernie Dodge) kā vienu no mācību metodēm izmantojot internetu. Pētījuma mērķis bija izpētīt, kā mācību modelis WebQuest var būt lietderīgs angļu valodas apguvē. Darba autore analizēja teorētisko literatūru par mācību modeļa WebQuest koncepciju un tā pielietojumu angļu valodas kā svešvalodas apguvē, izmantojot gadījuma pētījuma metodi. Pētījumā piedalīj...

  10. Normal hematopoiesis and lack of β-catenin activation in osteoblasts of patients and mice harboring Lrp5 gain-of-function mutations.

    Science.gov (United States)

    Galán-Díez, Marta; Isa, Adiba; Ponzetti, Marco; Nielsen, Morten Frost; Kassem, Moustapha; Kousteni, Stavroula

    2016-03-01

    Osteoblasts are emerging regulators of myeloid malignancies since genetic alterations in them, such as constitutive activation of β-catenin, instigate their appearance. The LDL receptor-related protein 5 (LRP5), initially proposed to be a co-receptor for Wnt proteins, in fact favors bone formation by suppressing gut-serotonin synthesis. This function of Lrp5 occurring in the gut is independent of β-catenin activation in osteoblasts. However, it is unknown whether Lrp5 can act directly in osteoblast to influence other functions that require β-catenin signaling, particularly, the deregulation of hematopoiesis and leukemogenic properties of β-catenin activation in osteoblasts, that lead to development of acute myeloid leukemia (AML). Using mice with gain-of-function (GOF) Lrp5 alleles (Lrp5(A214V)) that recapitulate the human high bone mass (HBM) phenotype, as well as patients with the T253I HBM Lrp5 mutation, we show here that Lrp5 GOF mutations in both humans and mice do not activate β-catenin signaling in osteoblasts. Consistent with a lack of β-catenin activation in their osteoblasts, Lrp5(A214V) mice have normal trilinear hematopoiesis. In contrast to leukemic mice with constitutive activation of β-catenin in osteoblasts (Ctnnb1(CAosb)), accumulation of early myeloid progenitors, a characteristic of AML, myeloid-blasts in blood, and segmented neutrophils or dysplastic megakaryocytes in the bone marrow, are not observed in Lrp5(A214V) mice. Likewise, peripheral blood count analysis in HBM patients showed normal hematopoiesis, normal percentage of myeloid cells, and lack of anemia. We conclude that Lrp5 GOF mutations do not activate β-catenin signaling in osteoblasts. As a result, myeloid lineage differentiation is normal in HBM patients and mice. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza. Published

  11. L’ange de l’Annonciation, chef de chœur dans Il Vangelo secondo Matteo de Pasolini

    Directory of Open Access Journals (Sweden)

    Sandra Gorgievski

    2012-07-01

    Full Text Available Médiateur par excellence entre le divin et le terrestre, l’ange – et l’épisode biblique de l’Annonciation en particulier, stimulent l’imaginaire contemporain, le mystère de l’incarnation ne pouvant être représenté mais figuré. S’appuyant sur le monde de références du spectateur – des textes source aux thèmes iconographiques médiévaux et renaissants (par exemple Giotto, Fra Angelico, Limbourg, del Cossa, Crivelli, della Francesca, L’Évangile selon saint Matthieu de Pasolini a principalement recours au son. De la musique sacrée (Bach, Misa Luba, Negro Spiritual et profane (Mozart, Prokofiev, Blind Willie Johnson aux chœurs qui fonctionnent comme des voix over, le film fait ‘entendre’ la présence angélique au spectateur. L’hybridité même des codes cinématographiques interroge le statut de l’image, tout en évoquant la présence immanente de l’ange –métaphore de l’indicible et l’inintelligible.Arch-mediator between the divine and the mundane, the angelic icon - and the Biblical episode of the Annunciation in particular - stimulate the contemporary imagination, as the mystery of the incarnation itself cannot be represented, but rather figured. Relying on the viewer’s world of references – from Biblical texts to Medieval and Renaissance iconography (Giotto, Fra Angelico, Limbourg, del Cossa, Crivelli, della Francesca among others, Pasolini also extensively resorts to sound in his Gospel According to St. Matthew. The film seeks to allow the viewer ‘hear’ angels, from sacred music (Bach, Misa Luba, Negro Spiritual, profane music (Mozart, Prokofiev, Blind Willie Johnson to choirs used as voice over. Hybrid cinematic devices question the status of images while they evoke the immanent presence of angels – metaphorically the unspeakable and unintelligible.

  12. Extramedullary hematopoiesis within the clivus: an unusual cause of lower cranial nerve palsy.

    Science.gov (United States)

    Reames, Davis L; Lindstrom, Katherine; Raghavan, Prashant; Jane, John

    2010-12-01

    We report one year follow up of a case of extramedullary hematopoiesis within the clivus. The imaging findings, brief clinical course, and endoscopic transphenoidal approach are described. A 29-year-old female with thalassemia developed worsening cranial nerve signs. After imaging studies discovered a large clival mass, she underwent endoscopic transphenoidal biopsy of the lesion. Neural compression from exuberant erythrogenesis within tissue normally quiescent of red blood cell production was found to be the etiology of her neural deficit. Treatment for this condition is generally non-operative unless significant neural compression is present. Radiotherapy and anti-neoplastic agents have been used with success.

  13. Adverse cardiac effects of exogenous angiotensin 1-7 in rats with subtotal nephrectomy are prevented by ACE inhibition.

    Directory of Open Access Journals (Sweden)

    Louise M Burrell

    Full Text Available We previously reported that exogenous angiotensin (Ang 1-7 has adverse cardiac effects in experimental kidney failure due to its action to increase cardiac angiotensin converting enzyme (ACE activity. This study investigated if the addition of an ACE inhibitor (ACEi to Ang 1-7 infusion would unmask any beneficial effects of Ang 1-7 on the heart in experimental kidney failure. Male Sprague-Dawley rats underwent subtotal nephrectomy (STNx and were treated with vehicle, the ACEi ramipril (oral 1mg/kg/day, Ang 1-7 (subcutaneous 24 μg/kg/h or dual therapy (all groups, n = 12. A control group (n = 10 of sham-operated rats were also studied. STNx led to hypertension, renal impairment, cardiac hypertrophy and fibrosis, and increased both left ventricular ACE2 activity and ACE binding. STNx was not associated with changes in plasma levels of ACE, ACE2 or angiotensin peptides. Ramipril reduced blood pressure, improved cardiac hypertrophy and fibrosis and inhibited cardiac ACE. Ang 1-7 infusion increased blood pressure, cardiac interstitial fibrosis and cardiac ACE binding compared to untreated STNx rats. Although in STNx rats, the addition of ACEi to Ang 1-7 prevented any deleterious cardiac effects of Ang 1-7, a limitation of the study is that the large increase in plasma Ang 1-7 with ramipril may have masked any effect of infused Ang 1-7.

  14. Angiotensin-(1-7) attenuates hyposmolarity-induced ANP secretion via the Na+-K+ pump.

    Science.gov (United States)

    Shah, Amin; Oh, Young-Bin; Shan, Gao; Song, Chang Ho; Park, Byung-Hyun; Kim, Suhn Hee

    2010-09-01

    The alteration in osmolarity challenges cell volume regulation, a vital element for cell survival. Hyposmolarity causes an increase in cell volume. Recently, it has been reported that the renin-angiotensin system (RAS) plays a role in cell volume regulation. We investigated the effect of angiotensin-(1-7) [Ang-(1-7)] on hyposmolarity-induced atrial natriuretic peptide (ANP) secretion in normal and diabetic (DM) rat atria and modulation of the effect of Ang-(1-7) by the Na(+)-K(+) pump. Using isolated control rat atria, we observed that perfusion of hyposmotic solution into the atria increased ANP secretion. When Ang-(1-7) [0.1 microM or 1 microM] was perfused in a hyposmolar solution, it decreased the hyposmolarity-induced ANP secretion in a dose-dependent manner. This effect of Ang-(1-7) could be mediated by the Na(+)-K(+) pump, since ouabain, an Na(+)-K(+) pump inhibitor, significantly decreased the effect of Ang-(1-7) on hyposmolarity-induced ANP secretion. In contrast, N(omega) Nitro-l-arginine methyl ester hydrochloride (l-NAME) did not modify the effect of Ang-(1-7) on the hyposmolarity-induced ANP secretion. Interestingly, the ANP secretion was increased robustly by the perfusion of the hyposmolar solution in the DM atria, as compared to the control atria. However, the inhibitory effect of Ang-(1-7) on the hyposmolarity-induced ANP secretion was not observed in the DM atria. In the DM atria, atrial contractility was significantly increased. Taken together, we concluded that Ang-(1-7) attenuated hyposmolarity-induced ANP secretion via the Na(+)-K(+) pump and a lack of Ang-(1-7) response in DM atria may partly relate to change in Na(+)-K(+) pump activity. Copyright 2010 Elsevier Inc. All rights reserved.

  15. The complex of PAMAM-OH dendrimer with Angiotensin (1–7) prevented the disuse-induced skeletal muscle atrophy in mice

    Science.gov (United States)

    Márquez-Miranda, Valeria; Abrigo, Johanna; Rivera, Juan Carlos; Araya-Durán, Ingrid; Aravena, Javier; Simon, Felipe; Pacheco, Nicolás; González-Nilo, Fernando Danilo; Cabello-Verrugio, Claudio

    2017-01-01

    Angiotensin (1–7) (Ang-(1–7)) is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues – among them, skeletal muscle – by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimer as an Ang-(1–7) carrier. Bioinformatics analysis showed that the Ang-(1–7)-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1–7) and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1–7)/PAMAM-OH complex, but not Ang-(1–7) alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1–7)/PAMAM-OH complex being intraperitoneally injected were similar to the results obtained when Ang-(1–7) was systemically administered through mini-osmotic pumps. Together, the results suggest that Ang-(1–7) can be protected for PAMAM-OH when this complex is intraperitoneally injected. Therefore, the Ang-(1–7)/PAMAM-OH complex is an efficient delivery method for Ang-(1–7), since it improves the anti-atrophic activity of this peptide in skeletal muscle. PMID:28331320

  16. Regulator of calcineurin 1 mediates pathological vascular wall remodeling

    Science.gov (United States)

    Esteban, Vanesa; Méndez-Barbero, Nerea; Jesús Jiménez-Borreguero, Luis; Roqué, Mercè; Novensá, Laura; Belén García-Redondo, Ana; Salaices, Mercedes; Vila, Luis; Arbonés, María L.

    2011-01-01

    Artery wall remodeling, a major feature of diseases such as hypertension, restenosis, atherosclerosis, and aneurysm, involves changes in the tunica media mass that reduce or increase the vessel lumen. The identification of molecules involved in vessel remodeling could aid the development of improved treatments for these pathologies. Angiotensin II (AngII) is a key effector of aortic wall remodeling that contributes to aneurysm formation and restenosis through incompletely defined signaling pathways. We show that AngII induces vascular smooth muscle cell (VSMC) migration and vessel remodeling in mouse models of restenosis and aneurysm. These effects were prevented by pharmacological inhibition of calcineurin (CN) or lentiviral delivery of CN-inhibitory peptides. Whole-genome analysis revealed >1,500 AngII-regulated genes in VSMCs, with just 11 of them requiring CN activation. Of these, the most sensitive to CN activation was regulator of CN 1 (Rcan1). Rcan1 was strongly activated by AngII in vitro and in vivo and was required for AngII-induced VSMC migration. Remarkably, Rcan1−/− mice were resistant to AngII-induced aneurysm and restenosis. Our results indicate that aneurysm formation and restenosis share mechanistic elements and identify Rcan1 as a potential therapeutic target for prevention of aneurysm and restenosis progression. PMID:21930771

  17. Neuroprotective Mechanisms of the ACE2-Angiotensin-(1-7)-Mas Axis in Stroke

    DEFF Research Database (Denmark)

    Bennion, Douglas M; Haltigan, Emily; Regenhardt, Robert W

    2015-01-01

    The discovery of beneficial neuroprotective effects of the angiotensin converting enzyme 2-angiotensin-(1-7)-Mas axis [ACE2-Ang-(1-7)-Mas] in ischemic and hemorrhagic stroke has spurred interest in a more complete characterization of its mechanisms of action. Here, we summarize findings that desc......The discovery of beneficial neuroprotective effects of the angiotensin converting enzyme 2-angiotensin-(1-7)-Mas axis [ACE2-Ang-(1-7)-Mas] in ischemic and hemorrhagic stroke has spurred interest in a more complete characterization of its mechanisms of action. Here, we summarize findings...... that describe the protective role of the ACE2-Ang-(1-7)-Mas axis in stroke, along with a focused discussion on the potential mechanisms of neuroprotective effects of Ang-(1-7) in stroke. The latter incorporates evidence describing the actions of Ang-(1-7) to counter the deleterious effects of angiotensin II...... complete understanding of the mechanisms of action of Ang-(1-7) to elicit neuroprotection will serve as an essential step toward research into potential targeted therapeutics in the clinical setting....

  18. Extramedullary pulmonary hematopoiesis causing pulmonary hypertension and severe tricuspid regurgitation detected by {sup 99m} technetium sulfur colloid bone marrow scan and single-photon emission computed tomography/CT

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Syed Zama; Clarke, Michael John; Kannivelu, Anbalagan; Chinchure, Dinesh; Srinivasan, Sivasubramanian [Dept. of Diagnostic Radiology, Khoo Teck Puat Hospital, Singapore (Singapore)

    2014-06-15

    Extramedullary pulmonary hematopoiesis is a rare entity with a limited number of case reports in the available literature only. We report the case of a 66-year-old man with known primary myelofibrosis, in whom a {sup 99m}technetium sulfur colloid bone marrow scan with single-photon emission computed tomography (SPECT)/CT revealed a pulmonary hematopoiesis as the cause of pulmonary hypertension and severe tricuspid regurgitation. To the best of our knowledge, this is the first description of {sup 99m} technetium sulfur colloid SPECT/CT imaging in this rare condition.

  19. Evaluation of angiopoietin 1 and 2, vascular endothelial growth factor, and tumor necrosis factor alpha levels in asthmatic children.

    Science.gov (United States)

    Köksal, Burcu Tahire; Ozbek, Ozlem Yilmaz; Bayraktar, Nilufer; Yazici, Ayse Canan

    2014-01-01

    Asthma is characterized by chronic airway inflammation that is associated with structural changes termed airway remodeling. Recently, cytokines/mediators that augment inflammation have been attracting attention in this field. The aim of this study was to evaluate serum angiopoietin (Ang)-1, Ang-2, vascular endothelial growth factor (VEGF), and tumor necrosis factor (TNF) alpha values, which have important roles in inflammation, angiogenesis, and remodeling in asthmatic children. We also documented correlations between demographic features, duration of asthma, and pulmonary function test (PFT) parameters. Randomly selected 40 children (20 male and 20 female children, aged 6-16 years) with mild or moderate persistent asthma and 32 healthy children (15 male and 17 female children, aged 6-16 years) enrolled in the study. All asthmatic children had been using inhaled corticosteroids at least for the last 3 months. Serum Ang-1 levels were significantly lower in asthmatic children than those in normal controls. The Ang-1/Ang-2 ratio was also significantly lower in asthmatic children compared with those in normal controls (p < 0.01). However, serum Ang-2, VEGF, and TNF-alpha levels were similar in the two groups. A significant positive correlation was found between VEGF and duration of asthma. No correlation between serum Ang-1, Ang-2, VEGF values, and PFT parameters was obtained. On the other hand, significant negative correlation was detected between serum TNF-alpha and forced expiratory volume in 1 second. We have shown that serum Ang-1 levels and Ang-1/Ang-2 ratio were significantly reduced and balance was toward Ang-2 in asthmatics children. This process may lead to inflammation, destabilization of blood vessels, and trigger remodeling.

  20. SELENIUM EFFECT UPON THE RATS' HEMATOPOIESIS IN THE SUBACUTE BENZENE INTOXICATION

    Directory of Open Access Journals (Sweden)

    Pavle Randjelovic

    2001-03-01

    Full Text Available The antioxidants (selenium, vitamins C and E stabilize the cell membrane andprotect the cells from the action of free radicals. On the other hand, the antioxidantsreduce the effects of chemical and physical agenls. Bcsidcs, selenium has animportant role in Transporting electrons in the mitochondria and il is necessary for iheglulathione peroxidase function in the protection from apoplhosis. Benzene is auniversal solvent and has a wide application in chemical industry. Its toxicity ismanifested in the damages done to the central nervous syslem, liver, kidneys andhematopoiesis system. Tn this experiment the Wistar rats were used that wereclassified in three experimental groups regarding the quantity of the receivedselenium. Each group comprised ten animals of both sexes and after two weeks'treatment by selenium of 4,8 and 16 mcg, the animals had received benzene byinlraperiloneal administration in the dose of 1,2 ml/kg of the body weight. Thecounting of the shaped blood elements was done after the selenium pretreatment andafter the benzene intoxication. The obtained results poinl to increased number of alithe blood elements after the selenium pretreatment while after benzene adminislrationthere was a drastic drop of the number of erylhrocyles and leukocytes alongwith moderate lhrombocylopenia. After the sacrifice, Ihe hematopoiesis organs weretaken. The hislological findings of the bone marrow show the emergence ofdisturbances, especially of the red sort cells as well as an obvious fat degeneration which is particularly conspicuous in the second and third groups of animals. Therewas also some damage done to the spleen, especially of its red pulp along with thepresence of a greater number of fresh erythrocytes in the second and third groups.Only the changes were more drastic in the third group. The obtained results show thatselenium in higher concentrations increases the number of erytrocytes andleukocytes which proves that it stimulates highly

  1. Grappling with the HOX network in hematopoiesis and leukemia.

    Science.gov (United States)

    McGonigle, Glenda J; Lappin, Terence R J; Thompson, Alexander

    2008-05-01

    The mammalian HOX gene network encodes a family of proteins which act as master regulators of developmental processes such as embryogenesis and hematopoiesis. The complex arrangement, regulation and co-factor association of HOX has been an area of intense research, particularly in cancer biology, for over a decade. The concept of redeployment of embryonic regulators in the neoplastic arena has received support from many quarters. Observations of altered HOX gene expression in various solid tumours and leukemia appear to support the thesis that 'oncology recapitulates ontogeny' but the identification of critical HOX subsets and their functional role in cancer onset and maintenance requires further investigation. The application of novel techniques and model systems will continue to enhance our understanding of the HOX network in the years to come. Better understanding of the intricacy of the complex as well as identification of functional pathways and direct targets of the encoded proteins will permit harnessing of this family of genes for clinical application.

  2. Correlation of serum cartilage oligomeric matrix protein (COMP) and interleukin-16 (IL-16) levels with disease severity in primary knee osteoarthritis: A pilot study in a Malaysian population.

    Science.gov (United States)

    Das Gupta, Esha; Ng, Wei Ren; Wong, Shew Fung; Bhurhanudeen, Abdul Kareem; Yeap, Swan Sim

    2017-01-01

    The aim of this study was to investigate the correlations between serum cartilage oligomeric matrix protein (COMP), interleukin-16 (IL-16) and different grades of knee osteoarthritis (KOA) in Malaysian subjects. Ninety subjects were recruited comprising 30 with Kellgren-Lawrence (K-L) grade 2 KOA, 27 with K-L grade 3 KOA, 7 with grade 4 KOA, and 30 healthy controls. All subjects completed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. Serum COMP and IL-16 levels were measured using ELISA and their values log transformed to ensure a normal distribution. There was no significant differences in levels of log serum COMP and IL-16 between healthy controls and KOA patients. There were no significant differences in the log serum COMP and IL-16 levels within the different K-L grades in the KOA patients. In KOA patients, log serum IL-16 levels significantly correlated with the WOMAC score (p = 0.001) and its subscales, pain (p = 0.005), stiffness (p = 0.019) and physical function (p<0.0001). Serum IL-16 levels were significantly higher in Malaysian Indians compared to Malays and Chinese (p = 0.024). In this multi-ethnic Malaysian population, there was no difference in serum COMP and IL-16 levels between healthy controls and patients with KOA, nor was there any difference in serum COMP or IL-16 levels across the various K-L grades of KOA. However, there were significant inter-racial differences in serum IL-16 levels.

  3. Do serum angiopoietin-1, angiopoietin-2, and their receptor Tie-2 and 4G/5G variant of PAI-1 gene have a role in the pathogenesis of preeclampsia?

    Science.gov (United States)

    Kamal, Manal; El-Khayat, Waleed

    2011-10-01

    To evaluate whether serum angiogenesis markers such as angiopoietins (Ang-1, Ang-2) and their receptor (Tie-2) are altered in women with preeclampsia. We also performed genotyping to determine if the 4G/5G genotypes of -675 PAI-1 gene may play a role in the pathogenesis of preeclampsia. Sixty-eight pregnant women with preeclampsia were compared to 35 normotensive pregnant women and 24 normotensive nonpregnant women in a cross-sectional study. Using enzyme-linked immunosorbent assay, levels of serum Ang-1 and Ang-2, and Tie-2 were measured. A single base pair insertion/deletion 4G/5G polymorphism of the PAI-1 gene was determined by polymerase chain reaction. Serum levels of Ang-1 and Tie-2 were significantly different among the study groups (P = 0.001 and P = 0.025, respectively) being lower in the preeclamptic group. Positive significant correlation was found between Ang-2 and Tie-2, (r = 0.26, P = 0.024). The frequency of the genotypes (4G/5G, 4G/4G, and 5G/5G) differed among the groups (P = 0.001). Also, the mean of systolic and diastolic blood pressures differed significantly according to the PAI-1 genotype being higher in those bearing the 4G allele; P = 0.04 and P = 0.023, respectively. Sera Ang-1 and Ang-2, and Tie-2 as well as variants of 4G/5G of PAI-1 polymorphism have positive implications in the pathogenesis of preeclampsia.

  4. Processamento de plásticos e materiais compósitos: comportamento mecânico de componentes em serviço

    OpenAIRE

    Capela, Carlos Alexandre Bento

    2010-01-01

    As vantagens dos materiais plásticos, tais como facilidade de processamento, baixo custo, alta produtividade e versatilidade, permite obter plásticos e materiais compósitos de matriz polimérica para um grande número de aplicações em engenharia. Os materiais compósitos são, actualmente, muito utilizados não só na indústria aeroespacial, mas, também, num crescente número de aplicações de Engenharia Mecânica, tais como componentes de máquinas, vasos de pressão, equipamentos industriais de proces...

  5. Efeito do condicionamento ambiental nas propriedades de cisalhamento e viscoelásticas de compósitos híbridos metal-fibra

    OpenAIRE

    Damato, Cesar Augusto [UNESP

    2010-01-01

    O desenvolvimento da tecnologia dos compósitos híbridos, combinando laminados poliméricos reforçados com fibras longas e placas metálicas, normalmente ligas de alumínio, denominados de CHMF, tem como uma de suas finalidades formar um conjunto de materiais que combine elevados valores de resistência mecânica, resistência ao impacto, rigidez e baixa massa específica. Essa combinação de propriedades torna os CHMF particularmente atrativos como substituintes das ligas metálicas e dos compósitos t...

  6. Avaliação dos modos de falha sob impacto de compósitos de matriz polimérica reforçados por fibras

    Directory of Open Access Journals (Sweden)

    Marcelo M. M. Naglis

    1998-03-01

    Full Text Available RESUMO: Neste trabalho é feita uma avaliação dos modos de falha de compósitos de matriz polimérica reforçados por fibras de vidro, carbono ou aramida, submetidos a carregamento dinâmico. Os compósitos unidirecionais analisados foram fabricados por prensagem e cura à vácuo de lâminas de pré-impregnados. A energia total absorvida na fratura mostrou uma correlação inversamente proporcional ao módulo elástico das fibras usadas como reforço. Os compósitos com fibras de carbono falharam de um modo frágil. Para estes compósitos o comportamento ao impacto pode ser modelado usando-se uma análise puramente elástica. Para os compósitos com fibras de vidro a falha foi controlada por um mecanismo misto de cisalhamento ao longo da interface fibra-matriz e tensão normal trativa atuando perpendicularmente às fibras. O modelo elástico empregado para simular o comportamento ao impacto subestima a energia absorvida por estes compósitos, porém, a diferença entre os valores experimentais e os calculados não ultrapassou 20 %. A falha dos compósitos com fibras aramidas foi atribuída, principalmente, ao componente de tensão trativa atuando perpendicularmente às fibras. Nestes compósitos foi observado arrancamento superficial nas fibras aramidas e o comportamento ao impacto não obedece o modelo elástico empregado.ABSTRACT: In this work an evaluation of the fracture mode of fiber reinforced resin matrix composites submitted to three point bending dynamic impact testing was undertaken. The unidirectional glass, carbon and aramid fiber-epoxy matrix composites used were fabricated by vacuum bagging prepreg laminas. The energy absorbed to fracture the composites had an inverse correlation to the fibres' elastic modulus. The carbon fiber composites failed in a brittle mode. The analysis of the fracture surfaces showed that for the glass fiber composites, the failure is controlled by a coupled mechanism of shear along the fiber

  7. Angiotensin-(1-7): Beyond the Cardio-Renal Actions

    DEFF Research Database (Denmark)

    Passos-Silva, Danielle G; Verano-Braga, Thiago; Santos, Robson AS

    2013-01-01

    and lipolysis while decreasing insulin resistance and dyslipidemia. Ang-(1-7) is also able to improve cerebroprotection against ischemic stroke, besides its effects on learning and memory. The reproductive system can also be affected by Ang-(1-7) treatment, with enhanced ovulation, spermatogenesis and sexual...... downstream effectors such as NO, FOXO1 and COX2. Through these mechanisms, Ang-(1-7) is able to improve pathological conditions such as fibrosis and inflammation in organs such as lungs, liver and kidney. In addition, this heptapeptide has positive effects in metabolism, increasing the glucose uptake...

  8. Hematopoiesis and hematopoietic organs in arthropods.

    Science.gov (United States)

    Grigorian, Melina; Hartenstein, Volker

    2013-03-01

    Hemocytes (blood cells) are motile cells that move throughout the extracellular space and that exist in all clades of the animal kingdom. Hemocytes play an important role in shaping the extracellular environment and in the immune response. Developmentally, hemocytes are closely related to the epithelial cells lining the vascular system (endothelia) and the body cavity (mesothelia). In vertebrates and insects, common progenitors, called hemangioblasts, give rise to the endothelia and blood cells. In the adult animal, many differentiated hemocytes seem to retain the ability to proliferate; however, in most cases investigated closely, the bulk of hemocyte proliferation takes place in specialized hematopoietic organs. Hematopoietic organs provide an environment where undifferentiated blood stem cells are able to self-renew, and at the same time generate offspring that differentiate into different blood cell types. Hematopoiesis in vertebrates, taking place in the bone marrow, has been subject to intensive research by immunologists and stem cell biologists. Much less is known about blood cell formation in invertebrate animals. In this review, we will survey structural and functional properties of invertebrate hematopoietic organs, with a main focus on insects and other arthropod taxa. We will then discuss similarities, at the molecular and structural level, that are apparent when comparing the development of blood cells in hematopoietic organs of vertebrates and arthropods. Our comparative review is intended to elucidate aspects of the biology of blood stem cells that are more easily missed when focusing on one or a few model species.

  9. Rakstīšanas procesa izmantošana angļu valodas mācīšanā

    OpenAIRE

    Zdanovska, Ināra

    2012-01-01

    Darbs veltīts rakstīšanas procesa izmantošanai angļu valodas mācīšanā pamatskolā. Izpētes mērķis ir izpētīt procesa rakstīšanas pieejas teorijas, procesa rakstīšanas modeļus, pielāgot piemērotāko modeli atbilstoši skolēnu vajadzībām un izmēģināt to angļu valodas stundās. Lai izpētītu adoptētā procesa rakstīšanas modeļa efektivitāti, tika pielietota atsevišķa gadījuma izpētes metode. Tā ietvēra adaptētā procesa rakstīšanas modeļa izmēģināšanu, skolēnu testēšanu, aptaujas, novērošanu, datu vākš...

  10. Efeito de aditivos desaerantes nas características de compósitos de epóxi/fibras de vidro

    Directory of Open Access Journals (Sweden)

    Alexsandro Oliveira

    2014-01-01

    Full Text Available A presença de vazios é um importante fator a afetar as propriedades de compósitos poliméricos. Existem várias causas para a formação de vazios, entre elas, o aprisionamento de gás (frequentemente gás úmido durante o processo de impregnação dos reforços fibrosos com resina e os voláteis gerados durante a formulação da resina. A quantidade de bolhas de ar aprisionadas pode ser, por vezes, reduzida se o sistema de resina é sujeito a um processo de desgaseificação por vácuo ou pelo uso de aditivos químicos especiais. O objetivo deste trabalho é investigar o efeito de um agente desaerante nas propriedades finais de compósitos de resina epóxi moldados pelo processo de RTM utilizando como reforço mantas e tecidos de fibras de vidro. Os compósitos produzidos foram avaliados quanto as suas propriedades de tração, flexão, dureza, short beam e análise dinâmico mecânica (DMA. Em geral, a utilização do aditivo desaerante não provocou alterações significativas nas propriedades mecânicas, tais como resistência e módulo de tração e flexão, as quais são determinadas principalmente pelo tipo e fração volumétrica de fibras. Contudo, os resultados de resistência ao cisalhamento e de dureza mostram um efeito positivo com a inclusão do agente desaerante, levando à melhora na qualidade dos compósitos.

  11. Idiopathic myelofibrosis accompanied by peritoneal extramedullary hematopoiesis presenting as refractory ascites in a dog.

    Science.gov (United States)

    Rautenbach, Yolandi; Goddard, Amelia; Clift, Sarah J

    2017-03-01

    A 2.5-year-old spayed female American Pit Bull Terrier dog presented with a primary complaint of chronic refractory ascites. The dog's CBC displayed a moderate to severe macrocytic, hypochromic, nonregenerative anemia, and a moderate leukopenia as result of a moderate neutropenia and monocytopenia. Microscopic examination of the blood smear showed marked anisocytosis, mild polychromasia, mild acanthocytosis and ovalocytosis, moderate schistocytosis and poikilocytosis, and 4 metarubricytes/100 WBC. Abdominal ultrasonography revealed a homogenous, mild to moderately hyperechoic appearing liver as well as marked amounts of speckled anechoic to slightly hypoechoic peritoneal fluid. Cytology of the ascitic fluid demonstrated a sterile transudate, with evidence of a chronic inflammatory reaction as well as erythroid and myeloid precursor cells, and a few megakaryocytes with occasional micromegakaryocytes. Histologic sections of bone marrow, spleen, and liver were examined, using routine H&E stains, as well as a variety of immunohistochemistry and other special stains. Histopathology of the bone marrow and spleen revealed varying degrees of fibrosis, erythroid, and myeloid hyperplasia, as well as multiple small hyperplastic clusters of megakaryocytes. The megakaryocytes displayed many features of atypia such as increased cytoplasmic basophilia and occasional abnormal chromatin clumping with mitoses. Histopathologic examination of the liver disclosed evidence of mild extramedullary hematopoiesis. This case represents the first report of canine idiopathic myelofibrosis associated with peritoneal extramedullary hematopoiesis, resulting in refractory ascites. Although idiopathic myelofibrosis is a relatively rare condition in dogs, this case demonstrates that ascites caused by peritoneal implants of hematopoietic tissue may be the initial manifestation of myelofibrosis. © 2016 American Society for Veterinary Clinical Pathology.

  12. Influência de Negro de Fumo Modificado com Polianilina na Estrutura de Compósitos com Poli(Fluoreto de Vinilideno

    Directory of Open Access Journals (Sweden)

    Zucolotto Valtencir

    2002-01-01

    Full Text Available Compósitos condutores elétricos a base de poli(fluoreto de vinilideno (PVDF e negro de fumo modificado com polianilina (Eeonomer® foram preparados através do processamento por fusão. Resultados de reometria de torque indicaram que a presença de polianilina no negro de fumo é vantajosa ao processamento por fusão, reduzindo a viscosidade do fundido em comparação com a aditivação com negro de fumo puro. Compósitos contendo acima de 5% em peso de Eeonomer® apresentaram condutividade da ordem de 10-2 S/cm. Esse valor se manteve estável mesmo após tratamento térmico a 150degreesC por 170 h em atmosfera ambiente. Análises por calorimetria diferencial de varredura (DSC e difração de Raios-X mostraram que o tipo e a quantidade de Eeonomer®, assim como a taxa de resfriamento da amostra, podem afetar a temperatura de fusão, o grau de cristalinidade e a fase cristalina do PVDF presente no compósito.

  13. Resistência ao Cisalhamento Interlaminar de Compósitos com Resina Epóxi com Diferentes Arranjos das Fibras na Presença de Vazios

    Directory of Open Access Journals (Sweden)

    Costa Michelle L.

    2001-01-01

    Full Text Available A presença de vazios em compósitos estruturais pode ter efeitos significativos. Em geral, os vazios diminuem a resistência estática e a vida em fadiga de laminados. Essa influência é bastante pronunciada na resistência ao cisalhamento interlaminar, compressão, entre outras, onde as propriedades mecânicas da matriz exercem maior influência sobre o comportamento do compósito. O presente artigo descreve o estudo do efeito da porosidade na resistência ao cisalhamento interlaminar de sistemas de compósitos de tecido e tape (fitas unidirecionais de carbono aglutinados com matriz epóxi. Os laminados foram produzidos de maneira semelhante, bem como o processo de introdução de vazios (na faixa de 0a 12% de porosidade.Os compósitos foram avaliados por análises microscópicas e inspeção ultra-sônica e os valores de atenuação medidos foram convertidos em coeficientes de absorção para permitir uma normalização dos dados. O critério de fratura de Mar-Lin apresentou bom ajuste, mostrando-se adequado para o estudo de porosidade em compósitos. Por meio desse critério foi determinado que somente os laminados com porosidade acima de 0,9% para tecido de carbono/epóxi e acima de 0,75% para laminados de tape de carbono/epóxi é que apresentam redução de suas propriedades mecânicas

  14. Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta

    Energy Technology Data Exchange (ETDEWEB)

    He, Rui-Qing; Tang, Xiao-Feng; Zhang, Bao-Li [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Shanghai Institute of Hypertension, Shanghai (China); Li, Xiao-Dong [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Shanghai Institute of Hypertension, Shanghai (China); Hong, Mo-Na [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Shanghai Institute of Hypertension, Shanghai (China); Chen, Qi-Zhi [Shanghai Institute of Hypertension, Shanghai (China); Han, Wei-Qing, E-mail: whan020@gmail.com [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Shanghai Institute of Hypertension, Shanghai (China); Gao, Ping-Jin, E-mail: gaopingjin@sibs.ac.cn [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Shanghai Institute of Hypertension, Shanghai (China)

    2016-04-29

    Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-β and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediated Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes. - Highlights: • Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation. • PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation. • Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs.

  15. Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta

    International Nuclear Information System (INIS)

    He, Rui-Qing; Tang, Xiao-Feng; Zhang, Bao-Li; Li, Xiao-Dong; Hong, Mo-Na; Chen, Qi-Zhi; Han, Wei-Qing; Gao, Ping-Jin

    2016-01-01

    Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-β and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediated Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes. - Highlights: • Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation. • PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation. • Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs.

  16. Influência do tratamento químico da fibra de bananeira em compósitos de poli(etileno-co-acetato de vinila com e sem agente de expansão

    Directory of Open Access Journals (Sweden)

    Matheus V. G. Zimmermann

    2014-01-01

    Full Text Available Neste trabalho foi avaliada a influência do tratamento alcalino na fibra de bananeira (FB e seu uso como agente de reforço em compósitos expandidos de poli(etileno-co-acetato de vinila - EVA. O processo de mistura dos compósitos ocorreu em um misturador de rolos aberto e após conformados e expandidos em uma prensa aquecida com moldes de volumes variáveis. Os compósitos foram avaliados por suas propriedades mecânicas, térmicas e morfológicas. Os resultados indicam que o tratamento alcalino promove a extração de componentes menos estáveis na FB, tais como a lignina, hemicelulose, ceras e óleos de baixo peso molecular. O uso da FB nos compósitos proporciona um decréscimo das propriedades mecânicas de resistência à tração e rasgo em relação ao EVA puro devido a moderadas propriedades de interface polímero-fibra. Nos compósitos expandidos, as propriedades mecânicas decrescem com a diminuição da densidade em função da maior presença de espaços vazios no interior dos compósitos, porém as propriedades mecânicas específicas de resistência ao rasgo apresentaram melhores resultados com 10 pcr de FB em todos os moldes utilizados.

  17. Mājas darbi angļu valodas stundās profesionālās vidusskolas skolēnu leksikas pilveidei

    OpenAIRE

    Zemskova, Nataļja

    2010-01-01

    Diplomdarbs tika izstrādāts, lai noskaidrotu, kā dažādi mājas darbi var pilnveidot studentu vārdu krājumu angļu valodas stundās profesionālajās vidusskolās. Mājasdarbi ir skolotāju un skolēnu ikdienas rutīna. Skolotājiem ir dažāda attieksme pret mājasdarbiem, bet skolēni sūdzas, ka mājasdarbi ir garlaicīgi un bezjēdzīgi. Diplomdarba mērķis bija izpētīt, kā skolēni var bagātināt savu profesionālo vārdu krājumu, pildot angļu valodas mājasdarbu profesionālajā vidusskolā. La...

  18. Extramedullary hematopoiesis of the conjunctiva presenting as active systemic disease in a patient with myelofibrosis.

    Science.gov (United States)

    Cuttler, Nirupa; Heidemann, David; Cendrowski, Christopher; Armin, Ali-Reza; Folberg, Robert

    2014-12-01

    To report the clinicopathological correlation of extramedullary hematopoiesis (EMH) of the conjunctiva in a patient with a history of myelofibrosis. Case report. Elevated pink conjunctival lesions developed bilaterally in a 73-year-old man who had been treated for myelofibrosis for 13 years. EMH was detected in the examination of tissue from the lesion of the inferior fornix of the right eye. The appearance of conjunctival lesions in a patient with myelofibrosis may indicate underlying pathology of EMH that may necessitate a change in systemic treatment of this condition.

  19. Extramedullary Hematopoiesis in a Man With β-Thalassemia: An Uncommon Cause of an Adrenal Mass

    Directory of Open Access Journals (Sweden)

    Zeighami

    2015-06-01

    Full Text Available Introduction Extramedullary hematopoiesis (EMH commonly occurs in the spleen, liver and lymph nodes. Rare cases of EMH in the adrenal gland have been reported. Case Presentation We report the case of a 33-year-old man from the South of Iran suffering from major β-thalassemia, who underwent open left adrenalectomy and the histopathology revealed EMH. Conclusions In patients in which a history of hematologic disorders exists, careful imaging and hormonal assay should be done to certify a diagnosis of EMH. However, the surgical management becomes inevitable in certain cases.

  20. Compósitos SiCf /SiC utilizados em sistemas de proteção térmica SiCf /SiC composites for thermal protection systems

    Directory of Open Access Journals (Sweden)

    M. Florian

    2005-09-01

    Full Text Available Compósitos de carbeto de silício (SiC reforçado com fibras de carbeto de silício (SiCf são materiais candidatos em potencial para utilização em sistemas de proteção térmica em altas temperaturas devido principalmente à boa condutividade térmica na direção da fibra e muito baixa condutividade térmica na direção transversal à fibra, alta dureza, estabilidade térmica e à corrosão por oxidação. O compósito SiCf/SiC possui uma matriz de SiC reforçada com fibras contínuas policristalinas de SiC e é obtido por reações de conversão em altas temperaturas e atmosfera controlada, utilizando o compósito carbono/carbono como precursor. O processo de Reação Química em Vapor (CVR foi utilizado para a fabricação de compósitos SiCf/SiC com alta pureza na fase de SiC-beta. O compósito precursor de carbono/carbono foi fabricado com fibra de carbono não estabilizada e matriz carbonosa derivada da resina fenólica na forma de carbono isotrópico. O compósito convertido exibiu uma densidade de 1,75 g/cm³, com 40% de porosidade aberta e resistência à flexão de 80 MPa medida por ensaio flexão em 4 pontos. A área especifica medida pela técnica de BET é dependente da temperatura de conversão e das condições inicias do precursor de carbono, podendo chegar a 18 m²/g.Composites based on silicon carbide are potential candidate materials for thermal protection systems mainly due to its good thermal conductivity in fiber direction and very low transversal thermal conductivity, high hardness, corrosion and thermal resistance. SiCf/SiC composite presents a SiC matrix reinforced with SiC polycrystalline continuous fibers. The composite was obtained by conversion reactions at high temperature and controlled atmosphere from a carbon/carbon composite precursor. The CVR process was used to fabricate SiC /SiC composite with crystalline high-purity beta-SiC from a carbon-carbon precursor fabricated with non-stabilized carbon fiber and

  1. Whole blood angiopoietin-1 and -2 levels discriminate cerebral and severe (non-cerebral malaria from uncomplicated malaria

    Directory of Open Access Journals (Sweden)

    Tangpukdee Noppadon

    2009-12-01

    Full Text Available Abstract Background Severe and cerebral malaria are associated with endothelial activation. Angiopoietin-1 (ANG-1 and angiopoietin-2 (ANG-2 are major regulators of endothelial activation and integrity. The aim of this study was to investigate the clinical utility of whole blood angiopoietin (ANG levels as biomarkers of disease severity in Plasmodium falciparum malaria. Methods The utility of whole blood ANG levels was examined in Thai patients to distinguish cerebral (CM; n = 87 and severe (non-cerebral malaria (SM; n = 36 from uncomplicated malaria (UM; n = 70. Comparative statistics are reported using a non-parametric univariate analysis (Kruskal-Wallis test or Chi-squared test, as appropriate. Multivariate binary logistic regression was used to examine differences in whole blood protein levels between groups (UM, SM, CM, adjusting for differences due to ethnicity, age, parasitaemia and sex. Receiver operating characteristic curve analysis was used to assess the diagnostic accuracy of the ANGs in their ability to distinguish between UM, SM and CM. Cumulative organ injury scores were obtained for patients with severe disease based on the presence of acute renal failure, jaundice, severe anaemia, circulatory collapse or coma. Results ANG-1 and ANG-2 were readily detectable in whole blood. Compared to UM there were significant decreases in ANG-1 (p Conclusions These results suggest that whole blood ANG-1/2 levels are promising clinically informative biomarkers of disease severity in malarial syndromes.

  2. Pecular Features of Hematopoiesis in the Liver of Mature and Immature Green Frogs (Pelophylax Esculentus Complex

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    Akulenko N. M.

    2016-12-01

    Full Text Available The article describes characteristic features of the hematopoiesis in mature and immature green frogs (Pelophylax esculentus complex. Quantitative differences in liver myelograms were insignificant. However, in a sample of mature animals numerous significant correlations between the number of pigment inclusions in the liver and indicators of erythropoiesis and myelopoiesis were observed. Those correlations were absent in the immature frogs. We concluded that aft er the frogs’ breeding a lack of plastic resources, in particular, hemosiderin remains up to the hibernation.

  3. Extramedullary hematopoiesis with spinal cord compression in a child with thalassemia intermedia.

    Science.gov (United States)

    Ileri, Talia; Azik, Fatih; Ertem, Mehmet; Uysal, Zumrut; Gozdasoglu, Sevgi

    2009-09-01

    Spinal cord compression due to extramedullary hematopoiesis is an extremely rare complication of thalassemia intermedia. No cases with this complication have been reported in the first decade of life, because masses of heterotropic marrow developed in patients as a result of continuous erythropoiesis. We report the 9-year-old patient suffering from thalassemia intermedia and presenting spinal cord compression. We also review the literature about treatment options, because there is no consensus about the optimal treatment of these patients. Our patient was successfully treated with radiation therapy followed by hydroxyurea. With this combination therapy, he had no recurrence during the 4-year follow-up period. Clinical awareness of this phenomenon with the early treatment is essential for optimizing the successful outcome.

  4. Extramedullary hematopoiesis and paraplegia in a patient with hemoglobin e-Beta thalassemia.

    Science.gov (United States)

    Alam, M R; Habib, M S; Dhakal, G P; Khan, M R; Rahim, M A; Chowdhury, A J; Mahmud, T K

    2010-07-01

    Extramedullary hematopoiesis (EMH) occurs in patients with various hematologic disorders involving a chronic increase in the production of red blood cells, and is often associated polycythemia vera and sickle cell anaemia, but is less common with thalassemia especially with hemoglobin E-beta thalassemia. Spinal cord compression due to EMH is a extremely rare complication of thalassemia and may present with paraparesis or paraplegia with or without sensory impairment. Treatment options mostly include surgery and/or radiotherapy. Whereas cases presenting with paraplegia have been treated with either surgery or radiotherapy with equal frequency and efficacy, almost all reported cases with paraplegia have been treated with surgery with or without radiation therapy. We hereby report a case of hemoglobin E-beta thalassemia with paraplegia treated successfully with radiotherapy.

  5. Fetal betamethasone exposure attenuates angiotensin-(1-7)-Mas receptor expression in the dorsal medulla of adult sheep.

    Science.gov (United States)

    Marshall, Allyson C; Shaltout, Hossam A; Nautiyal, Manisha; Rose, James C; Chappell, Mark C; Diz, Debra I

    2013-06-01

    Glucocorticoids including betamethasone (BM) are routinely administered to women entering into early preterm labor to facilitate fetal lung development and decrease infant mortality; however, fetal steroid exposure may lead to deleterious long term consequences. In a sheep model of fetal programming, BM-exposed (BMX) offspring exhibit elevated mean arterial pressure (MAP) and decreased baroreflex sensitivity (BRS) for control of heart rate by 0.5-years of age associated with changes in the circulating and renal renin-angiotensin systems (RAS). In the brain solitary tract nucleus, angiotensin (Ang) II actions through the AT1 receptor oppose the beneficial actions of Ang-(1-7) at the Mas receptor for BRS regulation. Therefore, we examined Ang peptides, angiotensinogen (Aogen), and receptor expression in this brain region of exposed and control offspring of 0.5- and 1.8-years of age. Mas protein expression was significantly lower (>40%) in the dorsal medulla of BMX animals at both ages; however, AT1 receptor expression was not changed. BMX offspring exhibited a higher ratio of Ang II to Ang-(1-7) (2.30±0.36 versus 0.99±0.28; p<0.01) and Ang II to Ang I at 0.5-years. Although total Aogen was unchanged, Ang I-intact Aogen was lower in 0.5-year BMX animals (0.78±0.06 vs. 1.94±0.41; p<0.05) suggesting a greater degree of enzymatic processing of the precursor protein in exposed animals. We conclude that in utero BM exposure promotes an imbalance in the central RAS pathways of Ang II and Ang-(1-7) that may contribute to the elevated MAP and lower BRS in this model. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Modèles et méthodologies d’analyse des compétences. Le double éclairage des pratiques et des recherches de Hajjar et Baubion-Broye

    Directory of Open Access Journals (Sweden)

    Jacques Leplat

    2005-11-01

    Full Text Available Le thème des compétences est d’actualité et de nombreuses disciplines se sentent concernées par son étude, notamment différentes spécialités de la psychologie, de l’ergonomie et de la sociologie. Octares témoigne de cet intérêt puisqu’il a déjà édité deux ouvrages sur ce thème : Leplat, J. et de Montmollin, M. (eds. (2001. Les compétences en ergonomie. Recueil de textes. Dupray, A., Guitton, C. & Monchatre, S. (eds.. (2003. Réfléchir la compétence. Approches sociologiques, juridiques, éco...

  7. Expression of angiopoietin-1 in hypoxic pericytes: Regulation by hypoxia-inducible factor-2α and participation in endothelial cell migration and tube formation.

    Science.gov (United States)

    Park, Yoon Shin; Kim, Gyungah; Jin, Yoon Mi; Lee, Jee Young; Shin, Jong Wook; Jo, Inho

    2016-01-08

    We previously reported that hypoxia increases angiopoietin-1 (Ang1), but not Ang2, mRNA expression in bovine retinal pericytes (BRP). However, the mechanism underlying Ang1 expression is unknown. Here, we report that Ang1 protein expression increased in hypoxic BRP in a dose- and time-dependent manner. This increase was accompanied by an increase in hypoxia-inducible factor-2α (HIF2α) expression. Transfection with an antisense oligonucleotide for HIF2α partially inhibited the hypoxia-induced increase in Ang1 expression. HIF2α overexpression further potentiated hypoxia-stimulated Ang1 expression, suggesting that HIF2α plays an important role in Ang1 regulation in BRP. When fused the Ang1 promoter (-3040 to +199) with the luciferase reporter gene, we found that hypoxia significantly increased promoter activity by 4.02 ± 1.68 fold. However, progressive 5'-deletions from -3040 to -1799, which deleted two putative hypoxia response elements (HRE), abolished the hypoxia-induced increase in promoter activity. An electrophoretic mobility shift assay revealed that HIF2α was predominantly bound to a HRE site, located specifically at nucleotides -2715 to -2712. Finally, treatment with conditioned medium obtained from hypoxic pericytes stimulated endothelial cell migration and tube formation, which was completely blocked by co-treatment with anti-Ang1 antibody. This study is the first to demonstrate that hypoxia upregulates Ang1 expression via HIF2α-mediated transcriptional activation in pericytes, which plays a key role in angiogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Reverse translation of phase I biomarker findings links the activity of angiotensin-(1–7) to repression of hypoxia inducible factor-1α in vascular sarcomas

    International Nuclear Information System (INIS)

    Petty, W Jeffrey; Aklilu, Mebea; Varela, Victor A; Lovato, James; Savage, Paul D; Miller, Antonius A

    2012-01-01

    In a phase I study of angiotensin-(1–7) [Ang-(1–7)], clinical benefit was associated with reduction in plasma placental growth factor (PlGF) concentrations. The current study examines Ang-(1–7) induced changes in biomarkers according to cancer type and investigates mechanisms of action engaged in vitro. Plasma biomarkers were measured prior to Ang-(1–7) administration as well as 1, 2, 3, 4, and 6 hours after treatment. Tests for interaction were performed to determine the impact of cancer type on angiogenic hormone levels. If a positive interaction was detected, treatment-induced biomarker changes for individual cancer types were assessed. To investigate mechanisms of action, in vitro growth assays were performed using a murine endothelioma cell line (EOMA). PCR arrays were performed to identify and statistically validate genes that were altered by Ang-(1–7) treatment in these cells. Tests for interaction controlled for dose cohort and clinical response indicated a significant impact of cancer type on post-treatment VEGF and PlGF levels. Following treatment, PlGF levels decreased over time in patients with sarcoma (P = .007). Treatment of EOMA cells with increasing doses of Ang-(1–7) led to significant growth suppression at doses as low as 100 nM. PCR arrays identified 18 genes that appeared to have altered expression after Ang-(1–7) treatment. Replicate analyses confirmed significant changes in 8 genes including reduction in PlGF (P = .04) and hypoxia inducible factor 1α (HIF-1α) expression (P < .001). Ang-(1–7) has clinical and pre-clinical activity for vascular sarcomas that is linked to reduced HIF-1α and PlGF expression

  9. PROCESS OF RECOVERING URANIUM

    Science.gov (United States)

    Carter, J.M.; Larson, C.E.

    1958-10-01

    A process is presented for recovering uranium values from calutron deposits. The process consists in treating such deposits to produce an oxidlzed acidic solution containing uranium together with the following imparities: Cu, Fe, Cr, Ni, Mn, Zn. The uranium is recovered from such an impurity-bearing solution by adjusting the pH of the solution to the range 1.5 to 3.0 and then treating the solution with hydrogen peroxide. This results in the precipitation of uranium peroxide which is substantially free of the metal impurities in the solution. The peroxide precipitate is then separated from the solution, washed, and calcined to produce uranium trioxide.

  10. Rcan1-1L overexpression induces mitochondrial autophagy and improves cell survival in angiotensin II-exposed cardiomyocytes

    International Nuclear Information System (INIS)

    Duan, Hongyan; Li, Yongqiang; Yan, Lijie; Yang, Haitao; Wu, Jintao; Qian, Peng; Li, Bing; Wang, Shanling

    2015-01-01

    Mitochondrial autophagy is an important adaptive stress response and can be modulated by various key molecules. A previous study found that the regulator of calcineurin 1-1L (Rcan1-1L) may regulate mitochondrial autophagy and cause mitochondria degradation in neurocytes. However, the effect of Rcan1-1L on cardiomyocytes has not been determined. In the present study, we aimed to investigate the role of Rcan1-1L in angiotensin II (Ang II)-exposed human cardiomyocytes. Above all, Human adult cardiac myocytes (HACMs) were exposed to 200 nmol/L Ang II for 4 days. Enhanced H 2 O 2 production, cytochrome C release and mitochondrial permeability were observed in these cells, which were blocked by valsartan. Consistently, Ang II exposure significantly reduced cardiomyocyte viability. However, transfection of Rcan1-1L vector promoted cell viability and ameliorated the apoptosis caused by Ang II. Rcan1-1L clearly promoted mitochondrial autophagy in HACMs, with elevated autophagy protein (ATG) 5 and light chain 3 (LC3) expression. Transient mitochondrial biogenesis and reduced cytochrome C release was also induced by Rcan1-1L. Additionally, Rcan1-1L significantly inhibited calcineurin/nuclear factor of activated T cells (NFAT) signaling. We thus conclude that Rcan1-1L may play a protective role in Ang II-treated cardiomyocytes through the induction of mitochondrial autophagy, and may be an alternative method of cardiac protection. - Highlights: • Transfection of Rcan1-1L into HACMs promoted cell viability and reduced apoptosis. • Transfection of Rcan1-1L promoted mitochondrial autophagy in HACMs. • Rcan1-1L inhibited the calcineurin/nuclear factor of activated T cells signaling

  11. Rcan1-1L overexpression induces mitochondrial autophagy and improves cell survival in angiotensin II-exposed cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Hongyan; Li, Yongqiang; Yan, Lijie; Yang, Haitao; Wu, Jintao; Qian, Peng; Li, Bing; Wang, Shanling, E-mail: shanglingwang@126.com

    2015-07-01

    Mitochondrial autophagy is an important adaptive stress response and can be modulated by various key molecules. A previous study found that the regulator of calcineurin 1-1L (Rcan1-1L) may regulate mitochondrial autophagy and cause mitochondria degradation in neurocytes. However, the effect of Rcan1-1L on cardiomyocytes has not been determined. In the present study, we aimed to investigate the role of Rcan1-1L in angiotensin II (Ang II)-exposed human cardiomyocytes. Above all, Human adult cardiac myocytes (HACMs) were exposed to 200 nmol/L Ang II for 4 days. Enhanced H{sub 2}O{sub 2} production, cytochrome C release and mitochondrial permeability were observed in these cells, which were blocked by valsartan. Consistently, Ang II exposure significantly reduced cardiomyocyte viability. However, transfection of Rcan1-1L vector promoted cell viability and ameliorated the apoptosis caused by Ang II. Rcan1-1L clearly promoted mitochondrial autophagy in HACMs, with elevated autophagy protein (ATG) 5 and light chain 3 (LC3) expression. Transient mitochondrial biogenesis and reduced cytochrome C release was also induced by Rcan1-1L. Additionally, Rcan1-1L significantly inhibited calcineurin/nuclear factor of activated T cells (NFAT) signaling. We thus conclude that Rcan1-1L may play a protective role in Ang II-treated cardiomyocytes through the induction of mitochondrial autophagy, and may be an alternative method of cardiac protection. - Highlights: • Transfection of Rcan1-1L into HACMs promoted cell viability and reduced apoptosis. • Transfection of Rcan1-1L promoted mitochondrial autophagy in HACMs. • Rcan1-1L inhibited the calcineurin/nuclear factor of activated T cells signaling.

  12. Serial CT Findings of Resolving Extramedullary Hematopoiesis as Unilateral Posterior Mediastinal Mass after Splenectomy in Hereditary Spherocytosis: A Case Report

    International Nuclear Information System (INIS)

    Nam, Mi Yeon; Lee, Ju Won; Kim, Yeo Ju; Kim, Youn Jeong; Kang, Young Hye; Lee, Kyung Hee

    2012-01-01

    Intrathoracic extramedullary hematopoiesis (EMH) is a rare condition of the hereditary spherocytosis. EMH usually regresses or disappears after treatment; such as splenectomy in the case of spherocytosis. We report a case of hereditary spherocytosis. It is presented with an unilateral paravertebral posterior mediastinal mass. After splenectomy, it revealed shrinkage and fatty replacement on serial CT scans.

  13. Serial CT Findings of Resolving Extramedullary Hematopoiesis as Unilateral Posterior Mediastinal Mass after Splenectomy in Hereditary Spherocytosis: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Mi Yeon; Lee, Ju Won; Kim, Yeo Ju; Kim, Youn Jeong; Kang, Young Hye; Lee, Kyung Hee [Dept. of Radiology, Inha University Hospital, Incheon (Korea, Republic of)

    2012-03-15

    Intrathoracic extramedullary hematopoiesis (EMH) is a rare condition of the hereditary spherocytosis. EMH usually regresses or disappears after treatment; such as splenectomy in the case of spherocytosis. We report a case of hereditary spherocytosis. It is presented with an unilateral paravertebral posterior mediastinal mass. After splenectomy, it revealed shrinkage and fatty replacement on serial CT scans.

  14. Angiotensin-(1-7 Promotes Resolution of Neutrophilic Inflammation in a Model of Antigen-Induced Arthritis in Mice

    Directory of Open Access Journals (Sweden)

    Lívia C. Barroso

    2017-11-01

    Full Text Available Defective resolution of inflammation may be crucial for the initiation and development of chronic inflammatory diseases, such as arthritis. Therefore, it has been suggested that therapeutic strategies based on molecules that facilitate inflammation resolution present great potential for the treatment of chronic inflammatory diseases. In this study, we investigated the effects and role of angiotensin-(1-7 [Ang-(1-7] in driving resolution of neutrophilic inflammation in a model of arthritis. For this purpose, male C57BL/6 mice were subjected to antigen-induced arthritis and treated with Ang-(1-7 at the peak of the inflammatory process. Analysis of the number of inflammatory cells, apoptosis, and immunofluorescence for NF-κB was performed in the exudate collected from the knee cavity. Neutrophil accumulation in periarticular tissue was measured by assaying myeloperoxidase activity. Apoptosis of human neutrophil after treatment with Ang-(1-7 was evaluated morphologically and by flow cytometry, and NF-κB phosphorylation by immunofluorescence. Efferocytosis was evaluated in vivo. Therapeutic treatment with Ang-(1-7 at the peak of inflammation promoted resolution, an effect associated with caspase-dependent neutrophils apoptosis and NF-κB inhibition. Importantly, Ang-(1-7 was also able to induce apoptosis of human neutrophils, an effect associated with NF-κB inhibition. The pro-resolving effects of Ang-(1-7 were inhibited by the Mas receptor antagonist A779. Finally, we showed that Ang-(1-7 increased the efferocytic ability of murine macrophages. Our results clearly demonstrate that Ang-(1-7 resolves neutrophilic inflammation in vivo acting in two key step of resolution: apoptosis of neutrophils and their removal by efferocytosis. Ang-(1-7 is a novel mediator of resolution of inflammation.

  15. Avaliação das propriedades mecânicas e morfológicas de compósitos de PEAD com pó de Pinus taeda e alumina calcinada

    Directory of Open Access Journals (Sweden)

    Karine Grison

    2015-08-01

    Full Text Available ResumoNeste estudo foram desenvolvidos compósitos utilizando PEAD, pó de madeira (Pinus taeda, alumina calcinada e dois diferentes tipos de agentes compatibilizantes para avaliação das propriedades morfológicas e mecânicas dos mesmos. Para aumentar a interação entre a matriz polimérica e o pó de madeira foram utilizados 2% de polietileno graftizado com anidrido maleico em todas as formulações. Para efeito comparativo foi desenvolvida uma formulação com viniltrietoxisilano como compatibilizante para a alumina calcinada. O teor de cargas variou de 4% a 33% para os compósitos de carga única e mantiveram o percentual de 28% para os compósitos com as duas cargas. A interação entre a matriz polimérica e as cargas, proporcionada pelo agente compatibilizante anidrido maleico, foi observada nas micrografias da interface da matriz/carga. A utilização do silano não proporcionou efeito adicional nas propriedades mecânicas dos compósitos. Os compósitos isentos de alumina apresentaram maior resistência à tração, porém na resistência à flexão a presença da alumina contribuiu para o aumento desta propriedade provavelmente devido à pequena interação existente entre a interface do seu grão e a matriz polimérica.

  16. The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and langendorff-perfused hearts

    DEFF Research Database (Denmark)

    Aplin, Mark; Christensen, Gitte Lund; Schneider, Mikael

    2007-01-01

    The angiotensin II (AngII) type 1 receptor (AT(1)R) has been shown to activate extracellular signal-regulated kinases 1 and 2 (ERK1/2) through G proteins or G protein-independently through beta-arrestin2 in cellular expression systems. As activation mechanisms may greatly influence the biological...... effects of ERK1/2 activity, differential activation of the AT(1)R in its native cellular context could have important biological and pharmacological implications. To examine if AT(1)R activates ERK1/2 by G protein-independent mechanisms in the heart, we used the [Sar(1), Ile(4), Ile(8)]-AngII ([SII] Ang......II) analogue in native preparations of cardiac myocytes and beating hearts. We found that [SII] AngII does not activate G(q)-coupling, yet stimulates the beta-arrestin2-dependent ERK1/2. The G(q)-activated pool of ERK1/2 rapidly translocates to the nucleus, while the beta-arrestin2-scaffolded pool remains...

  17. Heme oxygenase-1 gene expression modulates angiotensin II-induced increase in blood pressure.

    Science.gov (United States)

    Yang, Liming; Quan, Shuo; Nasjletti, Alberto; Laniado-Schwartzman, Michal; Abraham, Nader G

    2004-06-01

    The heme-heme oxygenase (HO) system has been implicated in the regulation of vascular reactivity and blood pressure. This study examines the notion that overexpression of HO decreases pressor responsiveness to angiotensin II (Ang II). Five-day-old Sprague-Dawley rats received an intraleft ventricular injection of approximately 5x10(9) cfu/mL of retroviruses containing human HO-1 sense (LSN-HHO-1), rat HO-1 antisense (LSN-RHO-1-AS), or control retrovirus (LXSN). Three months later, rats were instrumented with femoral arterial and venous catheters for mean arterial pressure (MAP) determination and Ang II administration, respectively. Rats injected with LSN-HHO-1, but not with LXSN, expressed human HO-1 mRNA and protein in several tissues. BP increased with administration of Ang II in rats expressing and not expressing human HO-1. However, the Ang II-induced pressor response (mm Hg) in LSN-HHO-1 rats (16+/-3, 27+/-3, and 38+/-3 at 0.5, 2, and 10 ng) was surpassed (PHHO-1 rats with the HO inhibitor tin mesoporphyrin (SnMP) enhanced (P<0.05) the Ang II-induced pressor response to a level not different from that observed in LXSN rats. Rats injected with LSN-RHO-1-AS showed a decrease in renal HO-1 protein expression and HO activity relative to control LXSN rats. Administration of Ang II (0.1 to 2 ng) caused small (4 to 5 mm Hg) but significant increases in MAP in rats injected with LSN-RHO-1-AS (P<0.05) compared with rats injected with LXSN. These data demonstrate that overexpression of HO-1 brings about a reduction in pressor responsiveness to Ang II, which is most likely due to increased generation of an HO-1 product, presumably CO, with the ability to inhibit vascular reactivity to constrictor stimuli.

  18. Electrochemical performance studies of MnO2 nanoflowers recovered from spent battery

    International Nuclear Information System (INIS)

    Ali, Gomaa A.M.; Tan, Ling Ling; Jose, Rajan; Yusoff, Mashitah M.; Chong, Kwok Feng

    2014-01-01

    Highlights: • MnO 2 is recovered from spent zinc–carbon batteries as nanoflowers structure. • Recovered MnO 2 nanoflowers show high specific capacitance. • Recovered MnO 2 nanoflowers show stable electrochemical cycling up to 900 cycles. • Recovered MnO 2 nanoflowers show low resistance in EIS data. - Abstract: The electrochemical performance of MnO 2 nanoflowers recovered from spent household zinc–carbon battery is studied by cyclic voltammetry, galvanostatic charge/discharge cycling and electrochemical impedance spectroscopy. MnO 2 nanoflowers are recovered from spent zinc–carbon battery by combination of solution leaching and electrowinning techniques. In an effort to utilize recovered MnO 2 nanoflowers as energy storage supercapacitor, it is crucial to understand their structure and electrochemical performance. X-ray diffraction analysis confirms the recovery of MnO 2 in birnessite phase, while electron microscopy analysis shows the MnO 2 is recovered as 3D nanostructure with nanoflower morphology. The recovered MnO 2 nanoflowers exhibit high specific capacitance (294 F g −1 at 10 mV s −1 ; 208.5 F g −1 at 0.1 A g −1 ) in 1 M Na 2 SO 4 electrolyte, with stable electrochemical cycling. Electrochemical data analysis reveal the great potential of MnO 2 nanoflowers recovered from spent zinc–carbon battery in the development of high performance energy storage supercapacitor system

  19. Structure Identification Using High Resolution Mass Spectrometry Data and the EPA’s CompTox Chemistry Dashboard (EAS)

    Science.gov (United States)

    The iCSS CompTox Dashboard is a publicly accessible dashboard provided by the National Center for Computation Toxicology at the US-EPA. It serves a number of purposes, including providing a chemistry database underpinning many of our public-facing projects (e.g. ToxCast and ExpoC...

  20. Activation of MEK 1/2 and p42/44 MAPK by Angiotensin II in Hepatocyte Nucleus and their Potentiation by Ethanol

    Science.gov (United States)

    Aroor, Annayya R.; Lee, Youn Ju; Shukla, Shivendra D.

    2009-01-01

    Hepato-subcellular effect of Ang II and ethanol on the p42/44 MAP Kinase and MEK1/2 were investigated in the nucleus of rat hepatocytes. Hepatocytes were treated with ethanol (100 mM) for 24 hr and stimulated with angiotensin II (Ang II, 100 nM, 5 min). The levels of p42/44 MAPK and MEK1/2 were monitored in the nuclear fraction using antibodies. Ang II itself caused significant accumulation of phospho-p42/44 MAPK in the nucleus without any significant translocation of p42/44 MAPK protein there by suggesting activation of p42/44 MAPK in the nucleus. Ang II caused marked accumulation of phospho-MEK 1/2 in the nucleus without any significant accumulation of MEK1/2 protein. Ratio of phospho-MEK 1/2 to MEK 1/2 protein in the nucleus after Ang II treatment was 2.4 times greater than control suggesting phosphorylation of MEK 1/2 inside the nucleus. Ethanol had no effect on the protein level or the activation of p42/44 MAPK in the nucleus. Ethanol treatment potentiated nuclear activation of p42/44 MPAK by Ang II but not translocation of p42/44 MAPK protein. This was accompanied by potentiation of Ang II stimulated accumulation of phospho-MEK 1/2 in the nucleus by ethanol. MEK 1/2 inhibitor, U-0126 inhibited Ang II response or its potentiation by ethanol. These results suggest that Ang II mediated accumulation of phospho-p42/44 MAPK in the hepatocyte nucleus involves MEK 1/2 dependent activation and this effect is potentiated by ethanol. PMID:19560630

  1. Chenu F. (2015). L’évaluation des compétences professionnelles. Une mise à l'épreuve des notions et présupposés théoriques sous-jacents

    OpenAIRE

    Wittorski, Richard

    2016-01-01

    Dans son ouvrage intitulé L’évaluation des compétences professionnelles, Florent Chenu s’intéresse à une question « chargée » tant sur le plan scientifique (définitions multiples du terme compétence, souvent aujourd’hui considéré comme un « mot valise ») que sur le plan social (des enjeux et débats sociaux vifs concernant les modalités d’évaluation des compétences et, au-delà, concernant la façon de les reconnaître dans les milieux du travail). Dans ce contexte particulier, proposer une publi...

  2. Pasaku elementu izmantošana angļu valodas kā svešvalodas mācīšanā

    OpenAIRE

    Sprukta, Kristīne

    2010-01-01

    Bakalaura tēma aplūko dažādus pasaku elementus un to pielietojumu angļu valodas kā svešvalodas mācīšanā. Pētījuma mērķis ir iedrošināt septīto klašu skolniekus radoši izpausties,rakstot pasakas angļu valodā. Bakalaura mērķis ir izpētīt, vai skolēni, rakstot savas pasakas, iespaidojas no esošajām vai arī rada jaunas idejas, lai izpaustu sevi. Darba metodes ir attiecīgās literatūras pētīšana un eksperimentālas mācību stundas kā gadījumpētījuma analīze Aizupes pamatskolā. Tika pierādīts, ka bērn...

  3. SIRT1 Functions as an Important Regulator of Estrogen-Mediated Cardiomyocyte Protection in Angiotensin II-Induced Heart Hypertrophy

    Directory of Open Access Journals (Sweden)

    Tao Shen

    2014-01-01

    Full Text Available Background. Sirtuin 1 (SIRT1 is a member of the sirtuin family, which could activate cell survival machinery and has been shown to be protective in regulation of heart function. Here, we determined the mechanism by which SIRT1 regulates Angiotensin II- (AngII- induced cardiac hypertrophy and injury in vivo and in vitro. Methods. We analyzed SIRT1 expression in the hearts of control and AngII-induced mouse hypertrophy. Female C57BL/6 mice were ovariectomized and pretreated with 17β-estradiol to measure SIRT1 expression. Protein synthesis, cardiomyocyte surface area analysis, qRT-PCR, TUNEL staining, and Western blot were performed on AngII-induced mouse heart hypertrophy samples and cultured neonatal rat ventricular myocytes (NRVMs to investigate the function of SIRT1. Results. SIRT1 expression was slightly upregulated in AngII-induced mouse heart hypertrophy in vivo and in vitro, accompanied by elevated cardiomyocyte apoptosis. SIRT1 overexpression relieves AngII-induced cardiomyocyte hypertrophy and apoptosis. 17β-Estradiol was able to protect cardiomyocytes from AngII-induced injury with a profound upregulation of SIRT1 and activation of AMPK. Moreover, estrogen receptor inhibitor ICI 182,780 and SIRT1 inhibitor niacinamide could block SIRT1’s protective effect. Conclusions. These results indicate that SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection during AngII-induced heart hypertrophy and injury.

  4. The complex of PAMAM-OH dendrimer with Angiotensin (1–7 prevented the disuse-induced skeletal muscle atrophy in mice

    Directory of Open Access Journals (Sweden)

    Márquez-Miranda V

    2017-03-01

    Full Text Available Valeria Márquez-Miranda,1,2,* Johanna Abrigo,3,4,* Juan Carlos Rivera,3,4 Ingrid Araya-Durán,1 Javier Aravena,3,4 Felipe Simon,3,4 Nicolás Pacheco,1 Fernando Danilo González-Nilo,1,2,5 Claudio Cabello-Verrugio3,4 1Center for Bioinformatics and Integrative Biology (CBIB, Facultad de Ciencias Biologicas, Universidad Andres Bello, Santiago, 2Fundación Fraunhofer Chile Research, Las Condes, 3Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas & Facultad de Medicina, Universidad Andres Bello, 4Millennium Institute on Immunology and Immunotherapy, Santiago, 5Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile *These authors contributed equally to this work Abstract: Angiotensin (1–7 (Ang-(1–7 is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues – among them, skeletal muscle – by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine (PAMAM-OH dendrimer as an Ang-(1–7 carrier. Bioinformatics analysis showed that the Ang-(1–7-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1–7 and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1–7/PAMAM-OH complex, but not Ang-(1–7 alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1–7/PAMAM-OH complex being intraperitoneally

  5. Extramedullary hematopoiesis presented as cytopenia and massive paraspinal masses leading to cord compression in a patient with hereditary persistence of fetal hemoglobin.

    Science.gov (United States)

    Katchi, Tasleem; Kolandaivel, Krishna; Khattar, Pallavi; Farooq, Taliya; Islam, Humayun; Liu, Delong

    2016-01-01

    Extramedullary hematopoeisis (EMH) can occur in various physiological and pathologic states. The spleen is the most common site of EMH. We report a case with hereditary persistence of fetal hemoglobin with extramedullary hematopoiesis presented as cord compression and cytopenia secondary to multi-paraspinal masses. Treatment can be a challenge. Relapse is a possibility.

  6. Compósitos à base de gesso com resíduos de EVA e vermiculita Gypsum-based composites with EVA waste and vermiculite

    Directory of Open Access Journals (Sweden)

    Marilia P. de Oliveira

    2012-06-01

    Full Text Available O gesso é um dos materiais de construção mais antigos de que se tem conhecimento. Algumas de suas propriedades lhes conferem vantagens, tais como resistência ao fogo e isolamentos térmico e acústico. Objetivou-se, com este trabalho, avaliar as propriedades físico-mecânicas de compósitos à base de gesso com a incorporação de resíduos da indústria de calçados, o etileno acetato de vinila (EVA e a vermiculita. O desenvolvimento desses compósitos tem como propósito a produção de elementos de revestimento para proteção térmica de alvenarias. Para determinar a influência dos teores de resíduo de EVA e vermiculita e da relação água/gesso nas propriedades massa específica aparente e nas resistências a flexão e a compressão, foram incorporados cinco diferentes percentuais desses materiais, combinados com três relações água/gesso. Os resultados foram analisados por meio da estatística multivariável e indicaram que a massa específica aparente de ambos os compósitos e a resistência à flexão do compósito com vermiculita, mostraram maior dependência da relação água/gesso; por sua vez, o percentual de agregado apresentou maior influência na resistência à flexão do compósito com EVA e na resistência a compressão de ambos os compósitos.Gypsum is one of the oldest known building materials. Some of its properties confer advantages such as fire resistance, thermal and acoustic insulation. This work aims to study the physical and mechanical properties of gypsum-based composite with the incorporation of residues from the footwear industry ethylene vinyl acetate (EVA and vermiculite. The aim to develop these composites is to produce components for thermal protection of masonry. To determine the influence of different residue levels of EVA and vermiculite, and the water/plaster ratio on the bulk density, flexural and compressive strength, five different percentages of these materials were incorporated combined with

  7. El vínculo entre sexualidad y violencia en el teatro de Angélica Liddell

    OpenAIRE

    Topolska, Ewelina Maria

    2014-01-01

    Angélica Liddell’s surge to (relative) fame in recent years (a process which began in 2000, peaking around 2008/09) resulted in an increasing number of articles being published about her theatre, not to mention a significant number of interviews she gave for the Spanish and international press. There is also a doctoral thesis by Ana Vidal Egea concerning Atra Bilis’ (the name of Liddell’s group) work. However, no existing study engaged in detailed analysis of the artist’s theatrical productio...

  8. Lipid rafts are required for signal transduction by angiotensin II receptor type 1 in neonatal glomerular mesangial cells

    Energy Technology Data Exchange (ETDEWEB)

    Adebiyi, Adebowale, E-mail: aadebiyi@uthsc.edu; Soni, Hitesh; John, Theresa A.; Yang, Fen

    2014-05-15

    Angiotensin II (ANG-II) receptors (AGTRs) contribute to renal physiology and pathophysiology, but the underlying mechanisms that regulate AGTR function in glomerular mesangium are poorly understood. Here, we show that AGTR1 is the functional AGTR subtype expressed in neonatal pig glomerular mesangial cells (GMCs). Cyclodextrin (CDX)-mediated cholesterol depletion attenuated cell surface AGTR1 protein expression and ANG-II-induced intracellular Ca{sup 2+} ([Ca{sup 2+}]{sub i}) elevation in the cells. The COOH-terminus of porcine AGTR1 contains a caveolin (CAV)-binding motif. However, neonatal GMCs express CAV-1, but not CAV-2 and CAV-3. Colocalization and in situ proximity ligation assay detected an association between endogenous AGTR1 and CAV-1 in the cells. A synthetic peptide corresponding to the CAV-1 scaffolding domain (CSD) sequence also reduced ANG-II-induced [Ca{sup 2+}]{sub i} elevation in the cells. Real-time imaging of cell growth revealed that ANG-II stimulates neonatal GMC proliferation. ANG-II-induced GMC growth was attenuated by EMD 66684, an AGTR1 antagonist; BAPTA, a [Ca{sup 2+}]{sub i} chelator; KN-93, a Ca{sup 2+}/calmodulin-dependent protein kinase II inhibitor; CDX; and a CSD peptide, but not PD 123319, a selective AGTR2 antagonist. Collectively, our data demonstrate [Ca{sup 2+}]{sub i}-dependent proliferative effect of ANG-II and highlight a critical role for lipid raft microdomains in AGTR1-mediated signal transduction in neonatal GMCs. - Highlights: • AGTR1 is the functional AGTR subtype expressed in neonatal mesangial cells. • Endogenous AGTR1 associates with CAV-1 in neonatal mesangial cells. • Lipid raft disruption attenuates cell surface AGTR1 protein expression. • Lipid raft disruption reduces ANG-II-induced [Ca{sup 2+}]{sub i} elevation in neonatal mesangial cells. • Lipid raft disruption inhibits ANG-II-induced neonatal mesangial cell growth.

  9. Maxillofacial extramedullary hematopoiesis in a child with sickle cell presenting as bilateral periorbital cellulitis.

    Science.gov (United States)

    Reiersen, David A; Mandava, Mamatha; Jeroudi, Majed; Gungor, Anil

    2014-07-01

    Review of a case of paraosseous extramedullary hematopoiesis (EMH) affecting the maxillary sinuses and retro-orbital spaces imitating bilateral orbital cellulitis. Maxillofacial EMH causes diagnostic/therapeutic challenges. This case report describes a 4-year-old African American male with sickle cell disease (HbSS) who presented with bilateral orbitofacial swelling. Diagnosis was made with imaging and confirmed with tissue sampling. Partial exchange transfusion was utilized to stop the progression of maxillofacial EMH and to treat the patient's chronic anemia. Follow-up MRI showed regression of orbital and retro-orbital involvement. Early treatment with conservative modalities and close observation may prevent need for more invasive treatments. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Angiotensin-(1-7 relieved renal injury induced by chronic intermittent hypoxia in rats by reducing inflammation, oxidative stress and fibrosis

    Directory of Open Access Journals (Sweden)

    W. Lu

    Full Text Available We aimed to study the renal injury and hypertension induced by chronic intermittent hypoxia (CIH and the protective effects mediated by angiotensin 1-7 [Ang(1-7]. We randomly assigned 32 male Sprague-Dawley rats (body weight 180-200 g to normoxia control, CIH, Ang(1-7-treated normoxia, and Ang(1-7-treated CIH groups. Systolic blood pressure (SBP was monitored at the start and end of each week. Renal sympathetic nerve activity (RSNA was recorded. CTGF and TGF-β were detected by immunohistochemistry and western blotting. Tissue parameters of oxidative stress were also determined. In addition, renal levels of interleukin-6, tumor necrosis factor-α, nitrotyrosine, and hypoxia-inducible factor-1α were determined by immunohistochemistry, immunoblotting, and ELISA. TUNEL assay results and cleaved caspase 3 and 12 were also determined. Ang(1-7 induced a reduction in SBP together with a restoration of RSNA in the rat model of CIH. Ang(1-7 treatment also suppressed the production of reactive oxygen species, reduced renal tissue inflammation, ameliorated mesangial expansion, and decreased renal fibrosis. Thus, Ang(1-7 treatment exerted renoprotective effects on CIH-induced renal injury and was associated with a reduction of oxidative stress, inflammation and fibrosis. Ang(1-7 might therefore represent a promising therapy for obstructive sleep apnea-related hypertension and renal injury.

  11. Engineered Murine HSCs Reconstitute Multi-lineage Hematopoiesis and Adaptive Immunity

    Directory of Open Access Journals (Sweden)

    Yi-Fen Lu

    2016-12-01

    Full Text Available Hematopoietic stem cell (HSC transplantation is curative for malignant and genetic blood disorders, but is limited by donor availability and immune-mismatch. Deriving HSCs from patient-matched embryonic/induced-pluripotent stem cells (ESCs/iPSCs could address these limitations. Prior efforts in murine models exploited ectopic HoxB4 expression to drive self-renewal and enable multi-lineage reconstitution, yet fell short in delivering robust lymphoid engraftment. Here, by titrating exposure of HoxB4-ESC-HSC to Notch ligands, we report derivation of engineered HSCs that self-renew, repopulate multi-lineage hematopoiesis in primary and secondary engrafted mice, and endow adaptive immunity in immune-deficient recipients. Single-cell analysis shows that following engraftment in the bone marrow niche, these engineered HSCs further specify to a hybrid cell type, in which distinct gene regulatory networks of hematopoietic stem/progenitors and differentiated hematopoietic lineages are co-expressed. Our work demonstrates engineering of fully functional HSCs via modulation of genetic programs that govern self-renewal and lineage priming.

  12. Deployed Flight Test of the Iraqi Air Force Comp Air 7SLX (CA-7)

    Science.gov (United States)

    2014-02-28

    been built with a castering nose wheel mounted to the engine mount, a simple yet effective design. The team purchased new engine mounts and castering ...nose wheels from Aero Comp Inc. to solve these problems on all the CA-7s they refurbished, which Fred Webster called “a pretty big modification .”22...from a Cessna 310. The UAE had made numerous other modifications .2 The United States Central Command Air Forces (CENTAF) was working with the

  13. FoRSIC : De l'ingénierie des compétences à l'ingénierie des connaissances.

    OpenAIRE

    Ertzscheid , Olivier; Link-Pezet , Jo; Lacombe , Elisabeth

    2002-01-01

    FoRSIC [1] est un dispositif d'ingénierie des connaissances, qui s'ancre dans le champ de la formation à la recherche documentaire. Après avoir précisé le contexte théorique qui le sous-tend, nous décrirons ici les méthodologies qui nous ont permis de faire émerger des représenta-tions structurantes et partageables de ce domaine, à l'aide d'une ontologie des compétences docu-mentaires que nous relions au réseau sémantique du modèle de domaine.

  14. Analyse in the patients with refractory heart purification treated by continuous blood purification

    International Nuclear Information System (INIS)

    Cai Xun; Huang Chengwen; Huang Zhongliang

    2006-01-01

    Objective: To investigate the application of continuous blood purification (CBP) and the effect of the angiotensin II (Ang II), aldosterone (ALD), atrial natriuretic peptide (ANP) in plasma with refractory heart failure (RHF) treated by CBP. Methods: 35 cases with RHF were treated by CBP. Blood pressure, heart rate, respiration, blood oxygen saturation, blood markers of biochemistry, blood gas analysis, left ventricle ejection fraction (LVEF), cardiac function and Ang II, ALD, ANF in plasma were checked before and after treatment. Results: the systolic pressure, diastolic pressure, heart rate, respiration, serum creatinine, blood urea nitroge, Ang II, ALD, ANF in plasma after treatment were significantly lower than those before treatment of CBP (P 3 - , PaO 2 , LVEF after treatment were significantly higher than those before treatment of CBP (P + , Na + , Cl - of blood serum were recovered normal after treatment, and cardiac function was recovered (P<0.05, P<0.01). Conclusion: In the patients with RHF, CBP can efficiently treat the water-electrolyte disturbance, keep the acid-base balance, decrease the levels of AngII, ALD, ANF in plasma, clear the inflammatory mediator and improve cardiac function. (authors)

  15. Effects of Dicto-Comp and Dictation on the Writing Skill of Female Adult Iranian EFL Learners

    Science.gov (United States)

    Adel, Rahil; Hashemian, Mahmood

    2015-01-01

    This study was an attempt to clarify and remind L2 learners/teachers of 2 kinds of writing: dicto-comp and dictation. We explored the effect of controlled writing on the accuracy of the writing of adult Iranian EFL learners. Prior to the study, the homogeneity of 30 adult EFL learners was checked through an OPT test. Thirty participants were…

  16. Role of insulin-like growth factor-1 (IGF-1) in regulating cell cycle progression

    International Nuclear Information System (INIS)

    Ma, Qi-lin; Yang, Tian-lun; Yin, Ji-ye; Peng, Zhen-yu; Yu, Min; Liu, Zhao-qian; Chen, Fang-ping

    2009-01-01

    Aims: Insulin-like growth factor-1 (IGF-1) is a polypeptide protein hormone, similar in molecular structure to insulin, which plays an important role in cell migration, cell cycle progression, cell survival and proliferation. In this study, we investigated the possible mechanisms of IGF-1 mediated cell cycle redistribution and apoptosis of vascular endothelial cells. Method: Human umbilical vein endothelial cells (HUVECs) were pretreated with 0.1, 0.5, or 2.5 μg/mL of IGF-1 for 30 min before the addition of Ang II. Cell cycle redistribution and apoptosis were examined by flow cytometry. Expression of Ang II type 1 (AT 1 ) mRNA and cyclin E protein were determined by RT-PCR and Western blot, respectively. Results: Ang II (1 μmol/L) induced HUVECs arrested at G 0 /G 1 , enhanced the expression level of AT 1 mRNA in a time-dependent manner, reduced the enzymatic activity of nitric oxide synthase (NOS) and nitric oxide (NO) content as well as the expression level of cyclin E protein. However, IGF-1 enhanced NOS activity, NO content, and the expression level of cyclin E protein, and reduced the expression level of AT 1 mRNA. L-NAME significantly counteracted these effects of IGF-1. Conclusions: Our data suggests that IGF-1 can reverse vascular endothelial cells arrested at G 0 /G 1 and apoptosis induced by Ang II, which might be mediated via a NOS-NO signaling pathway and is likely associated with the expression levels of AT1 mRNA and cyclin E proteins.

  17. Comparação do comportamento à flexão com restrições à deflexão de placas de compósitos de matriz polimérica epoxídica em função do tipo de fibra de reforço

    Directory of Open Access Journals (Sweden)

    Morais Willy A. de

    2003-01-01

    Full Text Available Placas finas de compósitos de matriz polimérica epoxídica reforçada por fibras de vidro, carbono ou aramida, bem como placas de um compósito híbrido vidro-aramida, foram submetidas a ensaios de flexão. As condições de fixação dos corpos de prova foram tais que o ensaios foram realizados com deflexão restrita. Os resultados experimentais obtidos para a deflexão máxima dos compósitos puderam ser qualitativamente previstos usando-se o método de balanço de energia de Ritz. Os compósitos reforçados por fibras de carbono apresentaram os maiores valores de energia de iniciação e de força máxima, o que foi atribuído às altas propriedades intrínsecas das fibras. As propriedades específicas do compósito híbrido foram superiores às dos compósitos apenas com fibras de vidro ou fibras aramidas. Este efeito sinergístico indicou um projeto adequado na fabricação deste compósito. O modo de falha macroscópico de todos os compósitos foi semelhante. Na face frontal, a interação compósito - punção seguiu o comportamento previsto pela Lei de Hertz. Na face posterior, houve preferencialmente delaminação.

  18. Extramedullary hematopoiesis presented as cytopenia and massive paraspinal masses leading to cord compression in a patient with hereditary persistence of fetal hemoglobin

    OpenAIRE

    Katchi, Tasleem; Kolandaivel, Krishna; Khattar, Pallavi; Farooq, Taliya; Islam, Humayun; Liu, Delong

    2016-01-01

    Background Extramedullary hematopoeisis (EMH) can occur in various physiological and pathologic states. The spleen is the most common site of EMH. Case presentation We report a case with hereditary persistence of fetal hemoglobin with extramedullary hematopoiesis presented as cord compression and cytopenia secondary to multi-paraspinal masses. Conclusion Treatment can be a challenge. Relapse is a possibility.

  19. Splenomegaly unresponsive to standard and salvage chemotherapy in Langerhans cell histiocytosis: a case of extramedullary hematopoiesis.

    Science.gov (United States)

    Christiansen, Ellen C; Ellwein, Marcine; Neglia, Joseph P

    2012-06-01

    Langerhans cell histiocytosis (LCH) is a proliferative disorder of dendritic cells which has evaded efforts to clearly define pathogenesis, diagnostic criteria, and therapeutic response markers. Strides have been made at classification with the recent development of a quantified score of disease severity. Splenic involvement is an indicator of poor prognosis, with spleen size its surrogate marker in evaluation and scoring. We describe a case of pediatric LCH with progressive splenomegaly despite treatment, which when examined at splenectomy revealed no LCH involvement but extramedullary hematopoiesis. These findings thus challenge our understanding of splenomegaly as a marker of disease. Copyright © 2011 Wiley Periodicals, Inc.

  20. Agglomeration and Deposition Behaviour of Solid Recovered Fuel

    DEFF Research Database (Denmark)

    Pedersen, Morten Nedergaard; Jensen, Peter Arendt; Nielsen, Mads

    2015-01-01

    Waste derived fuels such as Solid Recovered Fuel (SRF) are increasingly being used in the cement industry as a means to reduce cost [1]. SRF is produced by separating the combustible fraction from industrial or municipal solid waste (MSW). The recovered fraction has a higher content of combustibl...

  1. Oral delivery of Angiotensin-converting enzyme 2 and Angiotensin-(1-7) bioencapsulated in plant cells attenuates pulmonary hypertension.

    Science.gov (United States)

    Shenoy, Vinayak; Kwon, Kwang-Chul; Rathinasabapathy, Anandharajan; Lin, Shina; Jin, Guiying; Song, Chunjuan; Shil, Pollob; Nair, Anand; Qi, Yanfei; Li, Qiuhong; Francis, Joseph; Katovich, Michael J; Daniell, Henry; Raizada, Mohan K

    2014-12-01

    Emerging evidences indicate that diminished activity of the vasoprotective axis of the renin-angiotensin system, constituting angiotensin-converting enzyme 2 (ACE2) and its enzymatic product, angiotensin-(1-7) [Ang-(1-7)] contribute to the pathogenesis of pulmonary hypertension (PH). However, long-term repetitive delivery of ACE2 or Ang-(1-7) would require enhanced protein stability and ease of administration to improve patient compliance. Chloroplast expression of therapeutic proteins enables their bioencapsulation within plant cells to protect against gastric enzymatic degradation and facilitates long-term storage at room temperature. Besides, fusion to a transmucosal carrier helps effective systemic absorption from the intestine on oral delivery. We hypothesized that bioencapsulating ACE2 or Ang-(1-7) fused to the cholera nontoxin B subunit would enable development of an oral delivery system that is effective in treating PH. PH was induced in male Sprague Dawley rats by monocrotaline administration. Subset of animals was simultaneously treated with bioencapsulaed ACE2 or Ang-(1-7) (prevention protocol). In a separate set of experiments, drug treatment was initiated after 2 weeks of PH induction (reversal protocol). Oral feeding of rats with bioencapsulated ACE2 or Ang-(1-7) prevented the development of monocrotaline-induced PH and improved associated cardiopulmonary pathophysiology. Furthermore, in the reversal protocol, oral ACE2 or Ang-(1-7) treatment significantly arrested disease progression, along with improvement in right heart function, and decrease in pulmonary vessel wall thickness. In addition, a combination therapy with ACE2 and Ang-(1-7) augmented the beneficial effects against monocrotaline-induced lung injury. Our study provides proof-of-concept for a novel low-cost oral ACE2 or Ang-(1-7) delivery system using transplastomic technology for pulmonary disease therapeutics. © 2014 American Heart Association, Inc.

  2. The angiotensin-(1-7/Mas axis counteracts angiotensin II-dependent and –independent pro-inflammatory signaling in human vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Laura A Villalobos

    2016-12-01

    Full Text Available Background and aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7 is a member of the renin-angiotensin system (RAS that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7 to counteract human aortic smooth muscle cell (HASMC inflammation triggered by RAS-dependent and –independent stimuli, such as Ang II or interleukin (IL-1.Methods and Results: In cultured HASMC, the expression of iNOS and the release of nitric oxide were stimulated by both Ang II and IL-1, as determined by Western blot and indirect immunofluorescence or the Griess method, respectively. iNOS induction was inhibited by Ang-(1-7 in a concentration-dependent manner. This effect was equally blocked by two different Mas receptor antagonists, A779 and D-Pro7-Ang-(1-7, suggesting the participation of a unique Mas receptor subtype. Using pharmacological inhibitors, the induction of iNOS was proven to rely on the consecutive upstream activation of NADPH oxidase and NF-B. Indeed, Ang-(1-7 markedly inhibited the activation of the NADPH oxidase and subsequently of NF-B, as determined by lucigenin-derived chemiluminiscence and electromobility shift assay, respectively.Conclusion: Ang-(1-7 can act as a counter-regulator of the inflammation of vascular smooth muscle cells triggered by Ang II, but also by other stimuli beyond the RAS. Activating or mimicking the Ang-(1-7/Mas axis may represent a pharmacological opportunity to attenuate the pro-inflammatory environment that promotes and sustains the development of vascular diseases.

  3. Intrathoracic extramedullary hematopoiesis: appearance on /sup 99m/Tc sulfur colloid marrow scan

    International Nuclear Information System (INIS)

    Bronn, L.J.; Paquelet, J.R.; Tetalman, M.R.

    1980-01-01

    Imaging of the bone marrow by radionuclide scanning was performed using colloids, which are phagocytized by the reticuloendothelial cells of the marrow, or radioiron, which is incorporated into reticulocytes. The use of the former radiopharmaceutical is based on the assumption, generally valid except in aplastic states or after irradiation, that the distribution of hematopoietic and reticuloendothelial tissue in the marrow is similar. Regardless of the method used, active adult marrow is normally distributed only in the axial skeleton and proximal humeri and femurs. Marrow imaging has been used in the evaluation of myeloproliferative disorders, leukemia, lymphoma, aplastic states, malignancy metastatic to marrow, and hemolytic anemia. We report a case of thalassemia major in which the diagnosis of intrathoracic extramedullary hematopoiesis was confirmed with the /sup 99m/Tc sulfur colloid bone marrow scan

  4. Angiotensina-(1-7 durante o processo inicial na cascata da ovulação em bovinos Angiotensin-(1-7 during the initial process of ovulatory cascade in cattle

    Directory of Open Access Journals (Sweden)

    Joabel Tonellotto dos Santos

    2012-10-01

    Full Text Available O presente estudo teve como objetivo avaliar o efeito da Ang-(1-7 e de seu receptor (MAS na regulação da ovulação. No experimento I, utilizando um modelo in vitro de cultivo de células foliculares, foi avaliado o efeito do tratamento com Ang-(1-7 ou do bloqueio do receptor MAS através do inibidor d-Ala7-Ang-(1-7 (A-779 na expressão de RNAm para epirregulina (Ereg; um marcador inicial do processo de ovulação em células da granulosa. No experimento II, foi utilizado um modelo in vivo de injeção intrafolicular no qual vinte vacas tiveram o ciclo estral sincronizado e, quando os folículos atingiram um diâmetro mínimo de 12mm, foi realizada a injeção intrafolicular de A-779 ou solução salina 0,9%. No momento da injeção intrafolicular, foi realizada uma aplicação IM de análogo de GnRH. A suplementação com Ang-(1-7 ou o bloqueio de seu receptor MAS em sistema de cultivo de células da granulosa não alteraram o padrão de expressão de RNAm para Ereg. A aplicação intrafolicular de A-779 (10-5M não bloqueou a ovulação quando realizada antes do início do pico esperado de LH (100% das vacas ovularam nos grupos A-779 e controle, sugerindo que a Ang-(1-7 não possui papel relevante no início da cascata ovulatória em bovinos.This study aimed to evaluate the effect of Ang-(1-7 and its receptor (MAS in the regulation of the ovulatory cascade. In the experiment I, the effect of Ang-(1-7 or d-Ala7-Ang-(1-7 (A-779; Ang-(1-7 antagonist on the epirregulin (Ereg; initial marker of ovulation process mRNA expression in granulosa cells was assessed using an in vitro model of follicular cell culture. In experiment II, it was used an in vivo intrafollicular injection model, in which twenty cows had their follicular waves synchronized and the ovarian follicular size was daily monitored by ultrasound. Follicles that reached a minimum diameter of 12mm were injected with A-779 or saline 0.9%. At the time of the intrafollicular injection

  5. Effet sur la compétitivité des réglementations relatives à la gestion des effluents

    DEFF Research Database (Denmark)

    Andersen, Mikael Skou

    2004-01-01

    Grâce à un regard approfondi sur le secteur laitier dans les pays de l'OCDE, cette étude permet de mieux analyser l'impact des subventions à l'agriculture et des politiques de l'environnement sur l'environnement et sur la compétitivité internationale des produits laitiers. Ce chapitre étudie les ...

  6. Role of Mas receptor in renal blood flow response to angiotensin-(1-7) in ovariectomized estradiol treated rats.

    Science.gov (United States)

    Saberi, Shadan; Dehghani, Aghdas; Nematbakhsh, Mehdi

    2016-01-01

    The angiotensin 1-7 (Ang 1-7), is abundantly produced in kidneys and antagonizes the function of angiotensin II through Mas receptor (MasR) or other unknown mechanisms. In the current study, the role of MasR and steroid hormone estrogen on renal blood flow response to Ang 1-7 administration was investigated in ovariectomized (OV) female rats. OV female Wistar-rats received estradiol (500 μg/kg/week) or vehicle for two weeks. In the day of the experiment, the animals were anesthetized, cannulated, and the responses including mean arterial pressure, renal blood flow (RBF), and renal vascular resistance at the constant level of renal perfusion pressure to graded infusion of Ang 1-7 at 0, 100 and 300 ng/kg/min were determined in OV and OV estradiol-treated (OVE) rats, treated with vehicle or MasR antagonist; A779. RBF response to Ang 1-7 infusion increased dose-dependently in vehicle (Pdose <0.001) and A779-treated (Pdose <0.01) animals. However, when MasR was blocked, the RBF response to Ang 1-7 significantly increased in OV animals compared with OVE rats (P<0.05). When estradiol was limited by ovariectomy, A779 increased RBF response to Ang 1-7 administration, while this response was attenuated in OVE animals.

  7. Chronic Idiopathic Myelofibrosis Presenting as Cauda Equina Compression due to Extramedullary Hematopoiesis: A Case Report

    Science.gov (United States)

    Goh, Duck-Ho; Cho, Dae-Chul; Park, Seong-Hyun; Hwang, Jeong-Hyun; Sung, Joo-Kyung

    2007-01-01

    Extramedullary hematopoiesis (EMH) is occasionally reported in idiopathic myelofibrosis and is generally found in the liver, spleen, and lymph nodes several years after diagnosis. Myelofibrosis presenting as spinal cord compression, resulting from EMH tissue is very rare. A 39-yr-old man presented with back pain, subjective weakness and numbness in both legs. Sagittal magnetic resonance imaging showed multiple anterior epidural mass extending from L4 to S1 with compression of cauda equina and nerve root. The patient underwent gross total removal of the mass via L4, 5, and S1 laminectomy. Histological analysis showed islands of myelopoietic cells surrounded by fatty tissue, consistent with EMH, and bone marrow biopsy performed after surgery revealed hypercellular marrow and megakaryocytic hyperplasia and focal fibrosis. The final diagnosis was chronic idiopathic myelofibrosis leading to EMH in the lumbar spinal canal. Since there were no abnormal hematological findings except mild myelofibrosis, additional treatment such as radiothepary was not administered postoperatively for fear of radiotoxicity. On 6 month follow-up examination, the patient remained clinically stable without recurrence. This is the first case of chronic idiopathic myelofibrosis due to EMH tissue in the lumbar spinal canal in Korea. PMID:18162730

  8. Uranium material removing and recovering device

    International Nuclear Information System (INIS)

    Takita, Shin-ichi.

    1997-01-01

    A uranium material removing and recovering device for use in removing surplus uranium heavy metal (UO 2 ) generated in a uranium handling facility comprises a uranium material removing device and a uranium material recovering device. The uranium material removing device comprises an adsorbing portion filled with a uranium adsorbent, a control portion for controlling the uranium adsorbent of the uranium adsorbing portion by a controlling agent, a uranium adsorbing device connected thereto and a jetting device for jetting the adsorbing liquid to equipments deposited with uranium. The recovering device comprises a recovering apparatus for recovering uranium materials deposited with the adsorbent liquid removed by the jetting device and a recovering tank for storing the recovered uranium materials. The device of the present invention can remove surplus uranium simply and safely, mitigate body's load upon removing and recovering operations, facilitate the processing for the exchange of the adsorbent and reduces the radioactive wastes. (T.M.)

  9. Non-Radial Oscillation Modes of Superfluid Neutron Stars Modeled with CompOSE

    Directory of Open Access Journals (Sweden)

    Prashanth Jaikumar

    2018-03-01

    Full Text Available We compute the principal non-radial oscillation mode frequencies of Neutron Stars described with a Skyrme-like Equation of State (EoS, taking into account the possibility of neutron and proton superfluidity. Using the CompOSE database and interpolation routines to obtain the needed thermodynamic quantities, we solve the fluid oscillation equations numerically in the background of a fully relativistic star, and identify imprints of the superfluid state. Though these modes cannot be observed with current technology, increased sensitivity of future Gravitational-Wave Observatories could allow us to observe these oscillations and potentially constrain or refine models of dense matter relevant to the interior of neutron stars.

  10. Antenatal betamethasone attenuates the angiotensin-(1-7)-Mas receptor-nitric oxide axis in isolated proximal tubule cells.

    Science.gov (United States)

    Su, Yixin; Bi, Jianli; Pulgar, Victor M; Chappell, Mark C; Rose, James C

    2017-06-01

    We previously reported a sex-specific effect of antenatal treatment with betamethasone (Beta) on sodium (Na + ) excretion in adult sheep whereby treated males but not females had an attenuated natriuretic response to angiotensin-(1-7) [Ang-(1-7)]. The present study determined the Na + uptake and nitric oxide (NO) response to low-dose Ang-(1-7) (1 pM) in renal proximal tubule cells (RPTC) from adult male and female sheep antenatally exposed to Beta or vehicle. Data were expressed as percentage of basal uptake or area under the curve for Na + or percentage of control for NO. Male Beta RPTC exhibited greater Na + uptake than male vehicle cells (433 ± 28 vs. 330 ± 26%; P 0.05). Ang-(1-7) significantly inhibited Na + uptake in RPTC from vehicle male (214 ± 11%) and from both vehicle (190 ± 14%) and Beta (209 ± 11%) females but failed to attenuate Na + uptake in Beta male cells. Beta exposure also abolished stimulation of NO by Ang-(1-7) in male but not female RPTC. Both the Na + and NO responses to Ang-(1-7) were blocked by Mas receptor antagonist d-Ala 7 -Ang-(1-7). We conclude that the tubular Ang-(1-7)-Mas-NO pathway is attenuated in males and not females by antenatal Beta exposure. Moreover, since primary cultures of RPTC retain both the sex and Beta-induced phenotype of the adult kidney in vivo they appear to be an appropriate cell model to examine the effects of fetal programming on Na + handling by the renal tubules. Copyright © 2017 the American Physiological Society.

  11. Dynamical behavior of a three species food chain model with Beddington-DeAngelis functional response

    International Nuclear Information System (INIS)

    Naji, Raid Kamel; Balasim, Alla Tariq

    2007-01-01

    A three species food chain model with Beddington-DeAngelis functional response is investigated. The local stability analysis is carried out and global behavior is simulated numerically for a biologically feasible choice of parameters. The persistence conditions of a food chain model are established. The bifurcation diagrams are obtained for different parameters of the model after intensive numerical simulations. The results of simulations show that the model could exhibit chaotic dynamics for realistic and biologically feasible parametric values. Finally, the effect of immigration within prey species is investigated. It is observed that adding small amount of constant immigration to prey species stabilize the system

  12. Role of insulin-like growth factor-1 (IGF-1) in regulating cell cycle progression

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Qi-lin; Yang, Tian-lun [Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Yin, Ji-ye [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan (China); Peng, Zhen-yu [Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Yu, Min [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan (China); Liu, Zhao-qian, E-mail: liuzhaoqian63@126.com [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan (China); Chen, Fang-ping, E-mail: xychenfp@public.cs.hn.Cn [Department of Haematology, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China)

    2009-11-06

    Aims: Insulin-like growth factor-1 (IGF-1) is a polypeptide protein hormone, similar in molecular structure to insulin, which plays an important role in cell migration, cell cycle progression, cell survival and proliferation. In this study, we investigated the possible mechanisms of IGF-1 mediated cell cycle redistribution and apoptosis of vascular endothelial cells. Method: Human umbilical vein endothelial cells (HUVECs) were pretreated with 0.1, 0.5, or 2.5 {mu}g/mL of IGF-1 for 30 min before the addition of Ang II. Cell cycle redistribution and apoptosis were examined by flow cytometry. Expression of Ang II type 1 (AT{sub 1}) mRNA and cyclin E protein were determined by RT-PCR and Western blot, respectively. Results: Ang II (1 {mu}mol/L) induced HUVECs arrested at G{sub 0}/G{sub 1}, enhanced the expression level of AT{sub 1} mRNA in a time-dependent manner, reduced the enzymatic activity of nitric oxide synthase (NOS) and nitric oxide (NO) content as well as the expression level of cyclin E protein. However, IGF-1 enhanced NOS activity, NO content, and the expression level of cyclin E protein, and reduced the expression level of AT{sub 1} mRNA. L-NAME significantly counteracted these effects of IGF-1. Conclusions: Our data suggests that IGF-1 can reverse vascular endothelial cells arrested at G{sub 0}/G{sub 1} and apoptosis induced by Ang II, which might be mediated via a NOS-NO signaling pathway and is likely associated with the expression levels of AT1 mRNA and cyclin E proteins.

  13. A angústia, o nada e a morte em Heidegger Anguish, nothingness and death in Heidegger

    Directory of Open Access Journals (Sweden)

    Marco Aurélio Werle

    2003-01-01

    Full Text Available O artigo investiga a relação entre os conceitos de medo, angústia, nada e morte na filosofia da existência de Heidegger. Pretende-se apontar para o papel destes fenômenos existenciais na passagem do ser-aí desde a inautenticidade para a autenticidade de seu ser.This paper investigates the relationship between the concepts of fear, anguish, nothingness and death in Heidegger's philosophy of existence. It points to the role of these existential phenomena in the transformation of "Dasein", from the inauthenticity to the authenticity of its Being.

  14. Usinabilidade de materiais compósitos poliméricos para aplicações automotivas

    Directory of Open Access Journals (Sweden)

    Juan Carlos Horta Gutiérrez

    2014-12-01

    Full Text Available A cada dia o avanço tecnológico nos leva a encruzilhadas como a construção de veículos mais leves, com menor consumo de combustível e mais seguros. Neste sentido, materiais compósitos poliméricos são materiais usados atualmente em diferentes aplicações nas quais a leveza combinada com um alto módulo de elasticidade são características importantes. Poliamidas reforçadas com fibras de vidro se apresentam como materiais de grande futuro em aplicações automotivas. Desta forma, torna-se importante o estudo do comportamento deste tipo de material quando submetidos a processos de usinagem. Dentre os processos de usinagem o processo de furação é um dos mais utilizados nos componentes de material compósito. Neste trabalho será analisada a influência do avanço, da velocidade de corte e da geometria da ferramenta na força de avanço, pressão específica de corte e desvios dimensionais do furo realizado. Os testes foram realizados em poliamida sem reforço (PA6 e reforçada com 30% fibra de vidro (PA66-GF30 utilizando brocas de carbonetos sinterizados (K20 com ângulos de ponta diferente. Os resultados apontam claramente para a melhor usinabilidade do material reforçado em comparação ao sem reforço.

  15. Glucagon increase after chronic AT1 blockade is more likely related to an indirect leptin-dependent than to a pancreatic α-cell-dependent mechanism

    DEFF Research Database (Denmark)

    Mildner, Martin; Müller-Fielitz, Helge; Stölting, Ines

    2017-01-01

    II stimulation (0.01-100 μM) in α cells (InR1G9) and isolated murine islets. We determined plasma glucagon in rats that were chronically treated with AngII (9 μg/h) or the ARBs telmisartan (8 mg/kg/day) and candesartan (16 mg/kg/day) and correlated glucagon with additional hormones (e.g. leptin). Glucagon...... with AngII or candesartan and also when Sprague Dawley rats were treated with telmisartan in parallel to high-calorie feeding. Plasma glucagon and leptin negatively correlated in ARB-treated rats. The glucagon release from InR1G9 cells or islets after AngII, AngIV or Ang(1-7) is unspecific since it only...

  16. HSF1 phosphorylation by ERK/GSK3 suppresses RNF126 to sustain IGF-IIR expression for hypertension-induced cardiomyocyte hypertrophy.

    Science.gov (United States)

    Huang, Chih-Yang; Lee, Fa-Lun; Peng, Shu-Fen; Lin, Kuan-Ho; Chen, Ray-Jade; Ho, Tsung-Jung; Tsai, Fu-Jen; Padma, Vijaya V; Kuo, Wei-Wen; Huang, Chih-Yang

    2018-02-01

    Hypertension-induced cardiac hypertrophy and apoptosis are major characteristics of early-stage heart failure (HF). Inhibition of extracellular signal-regulated kinases (ERK) efficaciously suppressed angiotensin II (ANG II)-induced cardiomyocyte hypertrophy and apoptosis by blocking insulin-like growth factor II receptor (IGF-IIR) signaling. However, the detailed mechanism by which ANG II induces ERK-mediated IGF-IIR signaling remains elusive. Here, we found that ANG II activated ERK to upregulate IGF-IIR expression via the angiotensin II type I receptor (AT 1 R). ERK activation subsequently phosphorylates HSF1 at serine 307, leading to a secondary phosphorylation by glycogen synthase kinase III (GSK3) at serine 303. Moreover, we found that ANG II mediated ERK/GSK3-induced IGF-IIR protein stability by downregulating the E3 ubiquitin ligase of IGF-IIR RING finger protein CXXVI (RNF126). The expression of RNF126 decreased following ANG II-induced HSF1 S303 phosphorylation, resulting in IGF-IIR protein stability and increased cardiomyocyte injury. Inhibition of GSK3 significantly alleviated ANG II-induced cardiac hypertrophy in vivo and in vitro. Taken together, these results suggest that HSF1 phosphorylation stabilizes IGF-IIR protein stability by downregulating RNF126 during cardiac hypertrophy. ANG II activates ERK/GSK3 to phosphorylate HSF1, resulting in RNF126 degradation, which stabilizes IGF-IIR protein expression and eventually results in cardiac hypertrophy. HSF1 could be a valuable therapeutic target for cardiac diseases among hypertensive patients. © 2017 Wiley Periodicals, Inc.

  17. [Spinal cord compression due to extramedullary hematopoiesis in a patient with myelofibrosis].

    Science.gov (United States)

    Hijikata, Yasuhiro; Ando, Tetsuo; Inagaki, Tomonori; Watanabe, Hirohisa; Ito, Mizuki; Sobue, Gen

    2014-01-01

    Development and growth of hematopoietic tissue outside of the bone marrow is termed extramedullary hematopoiesis (EMH). It occurs in patients with hematological diseases such as myelofibrosis and thalassemia. Liver and spleen are the usual sites of EMH. However, spinal cord compression caused by EMH is a rare complication. A 65-year-old man with myelofibrosis was admitted to our hospital with progressive paraparesis. Thoracic spine MRI revealed epidural masses causing cord compression. Histological examination of the epidural mass showed evidence of EMH consisting of megakaryocytic and erythroid hyperplasia. After surgical decompression and radiotherapy, lower limb weakness and sensory disturbance were significantly improved. MRI showed disappearance of the spinal cord compression. With this therapy, he had no recurrence until he died of myelofibrosis. Spinal EMH should be considered as a differential diagnosis in patients with hematological diseases presenting with paraparesis. Surgical decompression and radiotherapy are effective approaches for the treatment of paraparesis due to EMH.

  18. Dicósimo, Daniel y Simonassi, Silvia (comp., Trabajadores y empresarios en la Argentina del siglo XX: indagaciones desde la historia social

    Directory of Open Access Journals (Sweden)

    Valeria Ianni

    2013-01-01

    Full Text Available Dicósimo, Daniel y Simonassi, Silvia (comp., Trabajadores y empresarios en la Argentina del siglo XX: indagaciones desde la historia social, Prohistoria ediciones, Rosario, 2011 (194 págs..

  19. Role of the spleen in cyclophosphamide-induced hematosuppression and extramedullary hematopoiesis in mice.

    Science.gov (United States)

    Wang, Yuli; Meng, Qinggang; Qiao, Haiquan; Jiang, Hongchi; Sun, Xueying

    2009-05-01

    Extramedullary hematopoiesis (EMH) is induced in spleens due to various diseases. The aim of this study is to investigate the role of spleen in cyclophosphamide (CTX)-induced hematosuppression and EMH in mice. Balb/c mice were IP injected with 300 mg/kg CTX 2 weeks after splenectomy or sham operation and randomly sacrificed 1, 3, 7, 14, and 21 days after injection. Blood samples were collected, and spleens were weighed, histologically analyzed, and then used for flow cytometry. There were significant differences in white blood count, red blood count, platelet numbers and hemoglobin concentration between the splenectomized and sham-operated mice after CTX injection. The cellularity of the spleen was reduced 3 days following CTX treatment but then rose 7 days after CTX treatment. The numbers of colony-forming units in the spleen reached a peak 7 days after CTX injection, then declined. Flow cytometry demonstrated the percentage of CD34(+) and CD117(+) cells in the spleen increased 7 days after CTX injection, indicating the hematopoietic stem and progenitor cells in the spleen. The study indicates that EMH occurs as a compensatory reaction to CTX-induced hematosuppression in the murine spleen, implying that conservation of the spleen may promote the recovery of cancer patients from chemotherapy-induced hematosuppression.

  20. Assignment of CSF-1 to 5q33.1: evidence for clustering of genes regulating hematopoiesis and for their involvement in the deletion of the long arm of chromosome 5 in myeloid disorders

    International Nuclear Information System (INIS)

    Pettenati, M.J.; Le Beau, M.M.; Lemons, R.S.; Shima, E.A.; Kawasaki, E.S.; Larson, R.A.; Sherr, C.J.; Diaz, M.O.; Rowley, J.D.

    1987-01-01

    The CSF-1 gene encodes a hematopoietic colony-stimulating factor (CSF) that promotes growth, differentiation, and survival of mononuclear phagocytes. By using somatic cell hybrids and in situ hybridization, the authors localized this gene to human chromosome 5 at bands q31 to q35, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, the CSF-1 gene was found to be deleted in the 5q- chromosome of a patient with refractory anemia who had a del(5) (q15q33.3) and in that of a second patient with acute nonlymphocytic leukemia de novo who had a similar distal breakpoint [del(5)(q13q33.3)]. The gene was present in the deleted chromosome of a third patient, with therapy-related acute nonlymphocytic leukemia, who had a more proximal breakpoint in band q33 [del(5)(q22q33.1)]. Hybridization of the CSF-1 probe to metaphase cells of a fourth patient, with acute nonlymphocytic leukemia de novo, who had a rearrangement of chromosomes 5 and 21 resulted in labeling of the breakpoint junctions of both rearranged chromosomes; this suggested that CSF-1 is located at 5q33.1. Thus, a small segment of chromosome 5 contains GM-CSF (the gene encoding the granulocyte-macrophage CSF), CSF-1, and FMS, which encodes the CSF-1 receptor, in that order from the centromere; this cluster of genes may be involved in the altered hematopoiesis associated with a deletion of 5q

  1. Automated evaluation of matrix elements between contracted wavefunctions: A Mathematica version of the FRODO program

    Science.gov (United States)

    Angeli, C.; Cimiraglia, R.

    2013-02-01

    ] hereafter to be referred to as papers I and II, respectively dedicated to the automated evaluation of the matrix elements of the molecular electronic Hamiltonian between internally contracted functions [3] (ICFs). In paper II the program FRODO (after Formal Reduction Of Density Operators) was presented with the purpose of providing working formulas for each occurrence of the ICFs. The original FRODO program was written in the MuPAD computer algebra system [4] and was actively used in our group for the generation of the matrix elements to be employed in the third-order n-electron valence state perturbation theory (NEVPT) [5-8] as well as in the internally contracted configuration interaction (IC-CI) [9]. We present a new version of the program FRODO written in the Mathematica system [10]. The reason for the rewriting of the program lies in the fact that, on the one hand, MuPAD does not seem to be any longer available as a stand-alone system and, on the other hand, Mathematica, due to its ubiquitousness, appears to be increasingly the computer algebra system most widely used nowadays. Restrictions: The program is limited to no more than doubly excited ICFs. Running time: The examples described in the Readme file take a few seconds to run. References: [1] C. Angeli, R. Cimiraglia, Comp. Phys. Comm. 166 (2005) 53. [2] C. Angeli, R. Cimiraglia, Comp. Phys. Comm. 171 (2005) 63. [3] H.-J. Werner, P. J. Knowles, Adv. Chem. Phys. 89 (1988) 5803. [4] B. Fuchssteiner, W. Oevel: http://www.mupad.de Mupad research group, university of Paderborn. Mupad version 2.5.3 for Linux. [5] C. Angeli, R. Cimiraglia, S. Evangelisti, T. Leininger, J.-P. Malrieu, J. Chem. Phys. 114 (2001) 10252. [6] C. Angeli, R. Cimiraglia, J.-P. Malrieu, J. Chem. Phys. 117 (2002) 9138. [7] C. Angeli, B. Bories, A. Cavallini, R. Cimiraglia, J. Chem. Phys. 124 (2006) 054108. [8] C. Angeli, M. Pastore, R. Cimiraglia, Theor. Chem. Acc. 117 (2007) 743. [9] C. Angeli, R. Cimiraglia, Mol. Phys. in press, DOI:10

  2. EPA:DHA 6:1 prevents angiotensin II-induced hypertension and endothelial dysfunction in rats: role of NADPH oxidase- and COX-derived oxidative stress.

    Science.gov (United States)

    Niazi, Zahid Rasul; Silva, Grazielle C; Ribeiro, Thais Porto; León-González, Antonio J; Kassem, Mohamad; Mirajkar, Abdur; Alvi, Azhar; Abbas, Malak; Zgheel, Faraj; Schini-Kerth, Valérie B; Auger, Cyril

    2017-12-01

    Eicosapentaenoic acid:docosahexaenoic acid (EPA:DHA) 6:1, an omega-3 polyunsaturated fatty acid formulation, has been shown to induce a sustained formation of endothelial nitric oxide (NO) synthase-derived NO, a major vasoprotective factor. This study examined whether chronic intake of EPA:DHA 6:1 prevents hypertension and endothelial dysfunction induced by angiotensin II (Ang II) in rats. Male Wister rats received orally corn oil or EPA:DHA 6:1 (500 mg kg -1 per day) before chronic infusion of Ang II (0.4 mg kg -1 per day). Systolic blood pressure was determined by tail cuff sphingomanometry, vascular reactivity using a myograph, oxidative stress using dihydroethidium and protein expression by immunofluorescence and western blot analysis. Ang II-induced hypertension was associated with reduced acetylcholine-induced relaxations of secondary branch mesenteric artery rings affecting the endothelium-dependent hyperpolarization (EDH)- and the NO-mediated relaxations, both of which were improved by the NADPH oxidase inhibitor VAS-2870. The Ang II treatment induced also endothelium-dependent contractile responses (EDCFs), which were abolished by the cyclooxygenase (COX) inhibitor indomethacin. An increased level of vascular oxidative stress and expression of NADPH oxidase subunits (p47 phox and p22 phox ), COX-1 and COX-2, endothelial NO synthase and Ang II type 1 receptors were observed in the Ang II group, whereas SK Ca and connexin 37 were downregulated. Intake of EPA:DHA 6:1 prevented the Ang II-induced hypertension and endothelial dysfunction by improving both the NO- and EDH-mediated relaxations, and by reducing EDCFs and the expression of target proteins. The present findings indicate that chronic intake of EPA:DHA 6:1 prevented the Ang II-induced hypertension and endothelial dysfunction in rats, most likely by preventing NADPH oxidase- and COX-derived oxidative stress.

  3. Effect of resin liners on the microleakage of class V dental composite restorations Efeito do uso de forradores resinosos sobre a microinfiltração de restaurações classe V em compósito odontológico

    Directory of Open Access Journals (Sweden)

    Roberta Caroline Bruschi Alonso

    2004-03-01

    Full Text Available PURPOSE: The aim of this study was to evaluate the effect of an adhesive applied in layers of different thickness or in association with a filled adhesive or with a low viscosity composite liner on the microleakage of composite restorations. METHODS: Forty bovine incisors were prepared with round cavities (4mm diameter X 2mm depth on the cementoenamel junction. The teeth were assigned to four groups according to the liner used: 1 (control - application of 1 layer of the Scotchbond Multi Purpose adhesive system (SBMP; 2 - application of 3 layers of SBMP; 3 - application of 1 layer of SBMP followed by application of one layer of Optibond FL adhesive; 4 - application of one layer of SBMP followed by application of flowable composite Flow-it. All cavities were restored using composite resin Z100. The microleakage test was conducted according to ISO (TR11405. Data were analyzed by Kruskall-Wallis test (a=0.05. RESULTS: Group 4 showed less leakage than Group 1. Groups 2 and 3 showed intermediate values and there were no statistical differences when they were compared to the values of Groups 1 and 4 CONCLUSION: The use of resin liners with flowable composites can reduce the microleakage of composite restorations.OBJETIVO: O objetivo desse estudo foi avaliar os efeitos da aplicação de um adesivo em diferentes espessuras ou em associação com um adesivo com carga ou com compósito de baixa viscosidade na microinfiltração marginal de restaurações com compósito odontológico. MÉTODOS: Quarenta incisivos bovinos foram selecionados e cavidades circulares (4mm de diâmetro X 2mm de profundidade foram preparadas na região da junção cemento-esmalte. Os dentes foram então divididos em quatro grupos de acordo com o forramento utilizado: 1: (controle aplicação do sistema de união Scotchbond Multi Uso (SBMU - 1 camada de adesivo; 2: aplicação de 3 camadas do adesivo SBMU; 3: aplicação do SBMU, seguido pela aplicação de uma camada do adesivo

  4. Angiotensin-(1?7) inhibits inflammation and oxidative stress to relieve lung injury induced by chronic intermittent hypoxia in rats

    OpenAIRE

    Lu, W.; Kang, J.; Hu, K.; Tang, S.; Zhou, X.; Yu, S.; Li, Y.; Xu, L.

    2016-01-01

    Obstructive sleep apnea is associated with inflammation and oxidative stress in lung tissues and can lead to metabolic abnormalities. We investigated the effects of angiotensin1–7 [Ang-(1–7)] on lung injury in rats induced by chronic intermittent hypoxia (CIH). We randomly assigned 32 male Sprague-Dawley rats (180–200 g) to normoxia control (NC), CIH-untreated (uCIH), Ang-(1–7)-treated normoxia control (N-A), and Ang-(1–7)-treated CIH (CIH-A) groups. Oxidative stress biomarkers were measured ...

  5. Dual repressive effect of angiotensin II-type 1 receptor blocker telmisartan on angiotensin II-induced and estradiol-induced uterine leiomyoma cell proliferation.

    Science.gov (United States)

    Isobe, Aki; Takeda, Takashi; Sakata, Masahiro; Miyake, Asako; Yamamoto, Toshiya; Minekawa, Ryoko; Nishimoto, Fumihito; Oskamoto, Yoko; Walker, Cheryl Lyn; Kimura, Tadashi

    2008-02-01

    Although uterine leiomyomas or fibroids are the most common gynecological benign tumor and greatly affect reproductive health and well-being, the pathophysiology and epidemiology of uterine leiomyomas are poorly understood. Elevated blood pressure has an independent, positive association with risk for clinically detected uterine leiomyoma. Angiotensin II (Ang II) is a key biological peptide in the renin-angiotensin system that regulates blood pressure. In this study, we investigated the potential role of Ang II (1-1000 nM) in the proliferation of rat ELT-3 leiomyoma cells in vitro. RT-PCR and western blot analysis with cell proliferation and DNA transfection assays were performed to determine the mechanism of action of Ang II. Ang II induced ELT-3 leiomyoma cell proliferation (P estradiol-induced cell proliferation (P < 0.01). AT(1)R, but not AT(2)R, plays a role in Ang II-induced ELT-3 cell proliferation. These experimental findings in vitro highlight the potential role of Ang II in the proliferation of leiomyoma cells.

  6. Effects of intraluteal implants of prostaglandin E1 or E2 on angiogenic growth factors in luteal tissue of Angus and Brahman cows.

    Science.gov (United States)

    Weems, Yoshie S; Ma, Yan; Ford, Stephen P; Nett, Terry M; Vann, Rhonda C; Lewis, Andrew W; Neuendorff, Don A; Welsh, Thomas H; Randel, Ronald D; Weems, Charles W

    2014-12-01

    Previously, it was reported that intraluteal implants containing prostaglandin E1 or E2 (PGE1 and PGE2) in Angus or Brahman cows prevented luteolysis by preventing loss of mRNA expression for luteal LH receptors and luteal unoccupied and occupied LH receptors. In addition, intraluteal implants containing PGE1 or PGE2 upregulated mRNA expression for FP prostanoid receptors and downregulated mRNA expression for EP2 and EP4 prostanoid receptors. Luteal weight during the estrous cycle of Brahman cows was reported to be lesser than that of Angus cows but not during pregnancy. The objective of this experiment was to determine whether intraluteal implants containing PGE1 or PGE2 alter vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), angiopoietin-1 (ANG-1), and angiopoietin-2 (ANG-2) protein in Brahman or Angus cows. On Day 13 of the estrous cycle, Angus cows received no intraluteal implant and corpora lutea were retrieved, or Angus and Brahman cows received intraluteal silastic implants containing vehicle, PGE1, or PGE2 on Day 13 and corpora lutea were retrieved on Day 19. Corpora lutea slices were analyzed for VEGF, FGF-2, ANG-1, and ANG-2 angiogenic proteins via Western blot. Day-13 Angus cow luteal tissue served as preluteolytic controls. Data for VEGF were not affected (P > 0.05) by day, breed, or treatment. PGE1 or PGE2 increased (P Angus cows compared with Day-13 and Day-19 Angus controls but decreased (P Angus controls. There was no effect (P > 0.05) of PGE1 or PGE2 on ANG-1 in Angus luteal tissue when compared with Day-13 or Day-19 controls, but ANG-1 was decreased (P Angus Vehicle controls when compared with Day-13 Angus controls, which was prevented (P Angus cows. There was no effect (P > 0.05) of PGE1 or PGE2 on ANG-2 in Brahman cows. PGE1 or PGE2 may alter cow luteal FGF-2, ANG-1, or ANG-2 but not VEGF to prevent luteolysis; however, species or breed differences may exist. Published by Elsevier Inc.

  7. Security Administrator Street Smarts A Real World Guide to CompTIA Security+ Skills

    CERN Document Server

    Miller, David R

    2011-01-01

    A step-by-step guide to the tasks involved in security administration If you aspire to a career in security administration, one of your greatest challenges will be gaining hands-on experience. This book takes you through the most common security admin tasks step by step, showing you the way around many of the roadblocks you can expect on the job. It offers a variety of scenarios in each phase of the security administrator's job, giving you the confidence of first-hand experience. In addition, this is an ideal complement to the brand-new, bestselling CompTIA Security+ Study Guide, 5th Edition o

  8. Role of Mas receptor in renal blood flow response to angiotensin (1-7) in male and female rats.

    Science.gov (United States)

    Nematbakhsh, Mehdi; Safari, Tahereh

    2014-01-01

    Epidemiologic and clinical studies have shown that progression of renal disease in male is faster than that in female. However, the exact mechanisms are not well recognized. Angiotensin (1-7) (Ang 1-7) receptor, called "Mas", is an element in the depressor arm of renin angiotensin system (RAS), and its expression is enhanced in females. We test the hypothesis that Mas receptor (MasR) blockade (A779) attenuates renal blood flow (RBF) in response to infusion of graded doses of Ang 1-7 in female rats. Male and female Wistar rats were anesthetized and catheterized. Then, the mean arterial pressure (MAP), RBF, and controlled renal perfusion pressure (RPP) responses to infusion of graded doses of Ang 1-7 (100-1000 ng/kg/min i.v.) with and without A779 were measured in the animals. Basal MAP, RPP, RBF, and renal vascular resistance (RVR) were not significantly different between the two groups. After Ang 1-7 administration, RPP was controlled at a constant level. However, RBF increased in a dose-related manner in response to Ang 1-7 infusion in both male and female rats (Pdoserenal diseases.

  9. Functional and Biochemical Endothelial Profiling In Vivo in a Murine Model of Endothelial Dysfunction; Comparison of Effects of 1-Methylnicotinamide and Angiotensin-converting Enzyme Inhibitor

    Science.gov (United States)

    Bar, Anna; Olkowicz, Mariola; Tyrankiewicz, Urszula; Kus, Edyta; Jasinski, Krzysztof; Smolenski, Ryszard T.; Skorka, Tomasz; Chlopicki, Stefan

    2017-01-01

    Although it is known that 1-methylnicotinamide (MNA) displays vasoprotective activity in mice, as yet the effect of MNA on endothelial function has not been demonstrated in vivo. Here, using magnetic resonance imaging (MRI) we profile the effects of MNA on endothelial phenotype in mice with atherosclerosis (ApoE/LDLR-/-) in vivo, in comparison to angiotensin (Ang) -converting enzyme (ACE) inhibitor (perindopril), with known vasoprotective activity. On a biochemical level, we analyzed whether MNA- or perindopril-induced improvement in endothelial function results in changes in ACE/Ang II-ACE2/Ang-(1–7) balance, and L-arginine/asymmetric dimethylarginine (ADMA) ratio. Endothelial function and permeability were evaluated in the brachiocephalic artery (BCA) in 4-month-old ApoE/LDLR-/- mice that were non-treated or treated for 1 month or 2 months with either MNA (100 mg/kg/day) or perindopril (10 mg/kg/day). The 3D IntraGate®FLASH sequence was used for evaluation of BCA volume changes following acetylcholine (Ach) administration, and for relaxation time (T1) mapping around BCA to assess endothelial permeability using an intravascular contrast agent. Activity of ACE/Ang II and ACE2/Ang-(1–7) pathways as well as metabolites of L-arginine/ADMA pathway were measured using liquid chromatography/mass spectrometry-based methods. In non-treated 6-month-old ApoE/LDLR-/- mice, Ach induced a vasoconstriction in BCA that amounted to –7.2%. 2-month treatment with either MNA or perindopril resulted in the reversal of impaired Ach-induced response to vasodilatation (4.5 and 5.5%, respectively) and a decrease in endothelial permeability (by about 60% for MNA-, as well as perindopril-treated mice). Improvement of endothelial function by MNA and perindopril was in both cases associated with the activation of ACE2/Ang-(1–7) and the inhibition of ACE/Ang II axes as evidenced by an approximately twofold increase in Ang-(1–9) and Ang-(1–7) and a proportional decrease in Ang II

  10. The US EPA CompTox Chemistry Dashboard as a source of data to fill data gaps for chemical sources of risk

    Science.gov (United States)

    Chemical risk assessment is both time-consuming and difficult because it requires the assembly of data for chemicals generally distributed across multiple sources. The US EPA CompTox Chemistry Dashboard is a publicly accessible web-based application providing access to various da...

  11. Sinterização ultrarrápida por micro-ondas de compósitos particulados PZT/FCO preparados por mistura em ultrassom

    Directory of Open Access Journals (Sweden)

    C. P. Fernandez

    Full Text Available Resumo Pós de Pb(Zr0,53Ti0,47O3 (PZT e Fe2CoO4 (FCO, foram sintetizados separadamente pelo método Pechini e misturados em ultrassom, nas proporções molares 80/20 e 50/50 (PZT/FCO. Os compósitos preparados foram prensados e submetidos à sinterização em forno convencional e sinterização ultrarrápida assistida por micro-ondas. A caracterização estrutural e microestrutural das amostras foram realizadas por difração de raios X e microscopia eletrônica de varredura, respectivamente. Medidas de constante dielétrica em função da temperatura, resistividade elétrica e coeficiente de acoplamento magnetoelétrico foram também realizadas. Os resultados evidenciaram que o método de mistura do PZT com a FCO por ultrassom foi rápido e eficiente, gerando, após sinterização, compósitos particulados com conectividade global (0-3 e distribuição uniforme de grãos da fase ferromagnética (FCO na matriz ferroelétrica (PZT. Da análise estrutural, verificou-se que a sinterização por micro-ondas propiciou um arranjo diferenciado no esquema de conectividade local na amostra (1-3 e (2-3, relacionada com a intensificação dos processos de difusão que ocorrem nesse tipo de sinterização principalmente em sistemas nanométricos. Pelos altos valores de resistividade obtidos, comprovou-se que a integridade das fases foi conservada nos dois métodos de sinterização, sendo mais eficiente na sinterização por micro-ondas, característica que garantiu o comportamento magnetoelétrico em todos os compósitos estudados neste trabalho. Os valores do campo Hmax foram dependentes da concentração da fase ferrita e da sinterização; para a composição 80/20 de 1,4 e 1,9 kOe, e para 50/50 de 3,5 e 3,0 kOe nas amostras sinterizadas por micro-ondas e convencionalmente, compatíveis com a literatura e que confirmaram a integridade das fases constituintes PZT e FCO.

  12. Development and validation of a real-time PCR assay for the detection of anguillid herpesvirus 1.

    Science.gov (United States)

    van Beurden, S J; Voorbergen-Laarman, M A; Roozenburg, I; van Tellingen, J; Haenen, O L M; Engelsma, M Y

    2016-01-01

    Anguillid herpesvirus 1 (AngHV1) causes a haemorrhagic disease with increased mortality in wild and farmed European eel, Anguilla anguilla (L.) and Japanese eel Anguilla japonica, Temminck & Schlegel). Detection of AngHV1 is currently based on virus isolation in cell culture, antibody-based typing assays or conventional PCR. We developed, optimized and concisely validated a diagnostic TaqMan probe based real-time PCR assay for the detection of AngHV1. The primers and probe target AngHV1 open reading frame 57, encoding the capsid protease and scaffold protein. Compared to conventional PCR, the developed real-time PCR is faster, less labour-intensive and has a reduced risk of cross-contamination. The real-time PCR assay was shown to be analytically sensitive and specific and has a high repeatability, efficiency and r(2) -value. The diagnostic performance of the assay was determined by testing 10% w/v organ suspensions and virus cultures from wild and farmed European eels from the Netherlands by conventional and real-time PCR. The developed real-time PCR assay is a useful tool for the rapid and sensitive detection of AngHV1 in 10% w/v organ suspensions from wild and farmed European eels. © 2015 John Wiley & Sons Ltd.

  13. The histone demethylase Jarid1b is required for hematopoietic stem cell self-renewal

    DEFF Research Database (Denmark)

    Stewart, Morag H; Albert, Mareike; Sroczynska, Patrycja

    2015-01-01

    Jarid1b/KDM5b is a histone demethylase that regulates self-renewal and differentiation in stem cells and cancer, however its function in hematopoiesis is unclear. Here, we find that Jarid1b is highly expressed in primitive hematopoietic compartments and is overexpressed in acute myeloid leukemias...... compromises hematopoietic stem cell (HSC) self-renewal capacity and suggest that Jarid1b is a positive regulator of HSC potential.......Jarid1b/KDM5b is a histone demethylase that regulates self-renewal and differentiation in stem cells and cancer, however its function in hematopoiesis is unclear. Here, we find that Jarid1b is highly expressed in primitive hematopoietic compartments and is overexpressed in acute myeloid leukemias....... Constitutive genetic deletion of Jarid1b did not impact steady-state hematopoiesis. In contrast, acute deletion of Jarid1b from bone marrow increased peripheral blood T cells and, following secondary transplantation, resulted in loss of bone marrow reconstitution. Our results reveal that deletion of Jarid1b...

  14. Recovering hydrocarbons with surfactants from lignin

    Energy Technology Data Exchange (ETDEWEB)

    Naae, D.G.; Whittington, L.E.; Ledoux, W.A.; Debons, F.E.

    1988-11-29

    This patent describes a method of recovering hydrocarbons from an underground hydrocarbon formation penetrated by at least one injection well and at least one production well, which comprises: injecting into the formation through an injection well a surfactant slug comprising about 0.1% to about 10% by weight of surfactants produced from lignin, the surfactants produced by placing lignin in contact with water, converting the lignin into low molecular weight lignin phenols by reducing the lignin in the presence of a reducing agent of carbon monoxide or hydrogen creating a reduction reaction mixture comprising oil soluble lignin phenols, the reduction occurring at a temperature greater than about 200/sup 0/C and a pressure greater than about 100 psi, recovering the oil soluble lignin phenols from the reduction mixture, and converting the lignin phenols into lignin surfactants by a reaction selected from the group consisting of alkoxylation, sulfonation, sulfation, aklylation, sulfomethylation, and alkoxysulfation; injecting into the formation through the injection well a drive fluid to push the surfactant slug towards a production well; and recovering hydrocarbons at the production well.

  15. Hydroxyurea as a first-line treatment of extramedullary hematopoiesis in patients with beta thalassemia: Four case reports.

    Science.gov (United States)

    Karimi, Mehran; Cohan, Nader; Pishdad, Parisa

    2015-01-01

    Extramedullary hematopoiesis (EMH) is evidenced by erythropoietic masses, which occurs as a compensatory mechanism to overcome hypoxia during chronic anemia. EMH masses in spinal cord could lead to cord compression and neurological symptoms. Besides transfusion, radiotherapy, and surgery, hydroxyurea (HU) is also a treatment strategy in EMH. We described four cases of beta thalassemia with EMH who were treated with HU as a monotherapy. INTERVENTION (AND TECHNIQUE): HU therapy was done in all patients without any transfusion during therapy. HU is a good treatment option for patients with EMH and it could be a substitute for radiotherapy and invasive surgery or regular blood transfusion.

  16. Beneficial Effects of Long-Term Administration of an Oral Formulation of Angiotensin-(1–7 in Infarcted Rats

    Directory of Open Access Journals (Sweden)

    Fúlvia D. Marques

    2012-01-01

    Full Text Available In this study was evaluated the chronic cardiac effects of a formulation developed by including angiotensin(Ang-(1–7 in hydroxypropyl β-cyclodextrin (HPβCD, in infarcted rats. Myocardial infarction (MI was induced by left coronary artery occlusion. HPβCD/Ang-(1–7 was administered for 60 days (76 μg/Kg/once a day/gavage starting immediately before infarction. Echocardiography was utilized to evaluate usual cardiac parameters, and radial strain method was used to analyze the velocity and displacement of myocardial fibers at initial time and 15, 30, and 50 days after surgery. Real-time PCR was utilized to evaluate the fibrotic signaling involved in the remodeling process. Once-a-day oral HPβCD/Ang-(1–7 administration improved the cardiac function and reduced the deleterious effects induced by MI on TGF-β and collagen type I expression, as well as on the velocity and displacement of myocardial fibers. These findings confirm cardioprotective effects of Ang-(1–7 and indicate HPβCD/Ang-(1–7 as a feasible formulation for long-term oral administration of this heptapeptide.

  17. Real-time prediction of Physicochemical and Toxicological Endpoints Using the Web-based CompTox Chemistry Dashboard (ACS Fall meeting) 10 of 12

    Science.gov (United States)

    The EPA CompTox Chemistry Dashboard developed by the National Center for Computational Toxicology (NCCT) provides access to data for ~750,000 chemical substances. The data include experimental and predicted data for physicochemical, environmental fate and transport and toxicologi...

  18. Cord Compression due to Extramedullary Hematopoiesis in an Adolescent with Known Beta Thalassemia Major

    Science.gov (United States)

    Soman, Salil; Rosenfeld, David L; Roychowdhury, Sudipta; Drachtman, Richard A; Cohler, Alan

    2009-01-01

    We describe a 16 year-old male with β thalassemia major and gait disturbances that had not been given blood transfusions due to a severe childhood transfusion reaction. Thoracic spine MRI demonstrated hematopoietic marrow throughout the spine and epidural masses causing cord compression consistent with extramedullary hematopoiesis (EMH). After treatment with steroids, radiotherapy and monitored blood transfusions, the patient demonstrated significant improvement of his paraspinal lesions and near complete resolution of his neurological symptoms. While EMH causing cord compression in adolescents is rare in the current era of bone marrow transplantation or chronic transfusions, it should be considered when thalassemia major patients present with neurological deficits. The well defined imaging features of EMH can play a central role in its diagnosis and management, especially because surgical and / or radiotherapeutic intervention are often considered in cases of failed medical treatment. PMID:22470615

  19. Spinal cord compression secondary to extramedullary hematopoiesis in a dog.

    Science.gov (United States)

    Williams, Lindsay M; Skeen, Todd M

    2013-03-15

    An 11-year-old spayed female Siberian Husky was evaluated because of a 2-week history of progressive paraparesis. Results of neurologic examination were consistent with a T3-L3 myelopathy. There were no abnormalities on CBC, and hypercalcemia was noted on serum biochemical analysis. Several hypoechoic splenic nodules were evident on abdominal ultrasonography, and results of fine-needle aspiration cytology were consistent with splenic extramedullary hematopoiesis (EMH). Two compressive, extradural masses in the dorsal epidural space of the thoracolumbar region of the spinal cord were seen on MRI images. A dorsal laminectomy was performed to remove the extradural spinal masses. Results of histologic examination of tissue samples were consistent with EMH. Following surgery, clinical signs of paraparesis resolved, and there was no recurrence of the masses 24 months after surgery. Extramedullary hematopoesis should be considered as a differential diagnosis in dogs in which results of diagnostic imaging indicate a epidural mass. In human patients, spinal EMH usually occurs secondary to an underlying hematologic disease, but it can also occur spontaneously. Treatment options reported for humans include surgical decompression, radiation therapy, chemotherapy, and blood transfusion. The dog of this report responded favorably to surgical decompression and was clinically normal 2 years after surgery.

  20. Efeito de diferentes fotopolimerizadores e meio de imersão na rugosidade e na cor de um compósito nanoparticulado

    Directory of Open Access Journals (Sweden)

    Suéllen Campos PLASTER

    Full Text Available Resumo Introdução O consumo excessivo de refrigerantes parece alterar as propriedades dos compósitos e essa alteração pode estar relacionada à unidade fotopolimerizadora. Objetivo Avaliar a alteração da rugosidade superficial (ΔR e da cor (ΔE de um compósito polimerizado por diferentes fotopolimerizadores, imerso em água destilada ou Coca-Cola®. Metodologia Sessenta amostras da resina nanoparticulada (FiltekMR Z350 XT, 3M foram distribuídas de acordo com as diferentes unidades de fotopolimerização: a luz halógena de quartzo-tungstênio-halogênio (QTH; b Luz de Emissão Diodo - LED 1 com ponteira de polímero; c LED 2 com ponteira de fibra ótica. Metade de cada grupo (n=10 foi mantida em água destilada ou imersa em Coca-Cola® 2×/dia por 20 minutos, durante 14 dias. Os dados foram submetidos aos testes Mann-Whitney e Kruskal-Wallis (p≤0,05. Resultado A ΔR não foi significante entre os grupos: em água: QTH = 0,006; LED 1 = 0,019; LED 2 = 0,010 (p=0,33; em refrigerante: QTH = 0,021; LED 1= 0,011; LED 2 = 0,030 (p=0,86. A ΔE não foi significativa entre os fotopolimerizadores: em água: QTH = 1,40; LED 1 = 1,80; LED 2 = 1,60 (p=0,31; em refrigerante: QTH = 2,51; LED 1= 1,91; LED 2 = 2,61 (p=0,41, mas foi significante comparando os meios de imersão (p=0,01, exceto para LED 1 (p=0,54. Conclusão As unidades fotopolimerizadoras não interferiram na rugosidade superficial e na cor da resina composta nanoparticulada. Os mergulhos diários em refrigerante não alteraram a lisura, mas alteraram a cor de modo visualmente perceptível, mas clinicamente aceitável, conforme os parâmetros da literatura científica.

  1. Stabilization of Angiotensin-(1-7) by key substitution with a cyclic non-natural amino acid.

    Science.gov (United States)

    Wester, Anita; Devocelle, Marc; Tallant, E Ann; Chappell, Mark C; Gallagher, Patricia E; Paradisi, Francesca

    2017-10-01

    Angiotensin-(1-7) [Ang-(1-7)], a heptapeptide hormone of the renin-angiotensin-aldosterone system, is a promising candidate as a treatment for cancer that reflects its anti-proliferative and anti-angiogenic properties. However, the peptide's therapeutic potential is limited by the short half-life and low bioavailability resulting from rapid enzymatic metabolism by peptidases including angiotensin-converting enzyme (ACE) and dipeptidyl peptidase 3 (DPP 3). We report the facile assembly of three novel Ang-(1-7) analogues by solid-phase peptide synthesis which incorporates the cyclic non-natural δ-amino acid ACCA. The analogues containing the ACCA substitution at the site of ACE cleavage exhibit complete resistance to human ACE, while substitution at the DDP 3 cleavage site provided stability against DPP 3 hydrolysis. Furthermore, the analogues retain the anti-proliferative properties of Ang-(1-7) against the 4T1 and HT-1080 cancer cell lines. These results suggest that ACCA-substituted Ang-(1-7) analogues which show resistance against proteolytic degradation by peptidases known to hydrolyze the native heptapeptide may be novel therapeutics in the treatment of cancer.

  2. Mass-Spectrometry Based Structure Identification of "Known-Unknowns" Using the EPA's CompTox Dashboard (ACS Spring National Meeting) 4 of 7

    Science.gov (United States)

    The CompTox Dashboard is a publicly accessible database provided by the National Center for Computational Toxicology at the US-EPA. The dashboard provides access to a database containing ~720,000 chemicals and integrates a number of our public-facing projects (e.g. ToxCast and Ex...

  3. Evidence for a cyclic AMP-dependent pathway in angiotensin AT1-receptor activation of human omental arteries

    Directory of Open Access Journals (Sweden)

    Hoa Ytterberg

    2001-03-01

    Full Text Available Enhanced responses to vasoconstriction induced by neuropeptide Y and α2-adrenoceptor agonists have been seen following pharmacological activation of the adenylyl cyclase (AC system. Since preliminary studies revealed only minor responses to angiotensin II (Ang II in human omental arteries, we have investigated whether enhanced activity of AC may unravel further functional Ang II receptors. Human omental arteries were obtained in conjunction with elective gut surgery. After dissection of the vessel, the endothelium was removed by 10 sec of Triton X-100 treatment. Ring segments (1—2 mm long were mounted on a myograph and studied. Ang II produced small contractions, 27±5% relative to the response elicited by 60 mM K+. However, enhanced Ang II (105±10%, p<0.001 responses were seen during AC activation by forskolin (0.11 µM. This enhanced contractile response to Ang II was not inhibited by the angiotensin II type 2 (AT2-receptor antagonist PD 123319 (0.1 µM, but was blocked in an insurmountable way by the angiotensin II type 1 (AT1-receptor antagonist candesartan (1 nM and in a surmountable manner by losartan (0.1 µM and irbesartan (0.1 µM. Pertussis toxin (a Gi-protein blocker and the protein kinase C inhibitor, RO31—8220 (0.01, 0.1 and 1 µM, markedly reduced this response, while the protein kinase A inhibitor, H89 (1, 10 µM, had no effect. RT-PCR provided evidence for the presence of mRNA for both AT1- and AT2-receptors. The results suggest that both a cAMP-dependent and a cAMP-independent mechanism are involved in the contractile responses to Ang II in human omental arteries and that both responses are mediated via the AT1-receptor.

  4. The Sirt1 activator SRT1720 attenuates angiotensin II-induced atherosclerosis in apoE{sup −/−} mice through inhibiting vascular inflammatory response

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yi xi; Zhang, Man; Cai, Yuehua; Zhao, Qihui; Dai, Wenjian, E-mail: wjdai@126.com

    2015-10-02

    Activation of the silent mating type information regulation 2 homolog 1 (SIRT1) has been shown consistent antiinflammatory function. However, little information is available on the function of SIRT1 during Angiotensin II (AngII)-induced atherosclerosis. Here we report atheroprotective effects of sirt1 activation in a model of AngII-accelerated atherosclerosis, characterized by suppression pro-inflammatory transcription factors Nuclear transcription factor (NF)-κB and Signal Transducers and Activators of Transcription. (STAT) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the SIRT1 agonist SRT1720 substantially attenuated AngII-accelerated atherosclerosis with decreasing blood pressure and inhibited NF-κB and STAT3 activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in AngII-treated VSMCs and macrophages: SIRT1 activation inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of AngII and highlight actions of SIRT1 activation to inhibit AngII signaling, which is atheroprotective. - Highlights: • SRT1720 reduced atherosclerotic lesion size in aortic arches and atherosclerotic lesion macrophage content. • SRT1720 could inhibit the phosphorylation of STAT3 and p65 phosphorylation and translocation. • SRT1720 could inhibit the expression of proinflammatory factor.

  5. Increased Functional Half-life of Fibroblast Growth Factor-1 by Recovering a Vestigial Disulfide Bond

    Directory of Open Access Journals (Sweden)

    Jihun Lee

    2010-12-01

    Full Text Available The fibroblast growth factor (FGF family of proteins contains an absolutely conserved Cys residue at position 83 that is present as a buried free cysteine. We have previously shown that mutation of the structurally adjacent residue, Ala66, to cysteine results in the formation of a stabilizing disulfide bond in FGF-1. This result suggests that the conserved free cysteine residue at position 83 in the FGF family of proteins represents a vestigial half-cystine. Here, we characterize the functional half-life and mitogenic activity of the oxidized form of the Ala66Cys mutation to identify the effect of the recovered vestigial disulfide bond between Cys83 and Cys66 upon the cellular function of FGF-1. The results show that the mitogenic activity of this mutant is significantly increased and that its functional half-life is greatly extended. These favorable effects are conferred by the formation of a disulfide bond that simultaneously increases thermodynamic stability of the protein and removes a reactive buried thiol at position 83. Recovering this vestigial disulfide by introducing a cysteine at position 66 is a potentially useful protein engineering strategy to improve the functional half-life of other FGF family members.

  6. Compósito de colágeno com silicato e hidroxiapatita como material para endodontia: preparação e caracterização = Collagen composite with silicate and hydroxyapatite as endodontic material: preparation and characterization

    Directory of Open Access Journals (Sweden)

    E'Gues, Miguel Antônio Menezes

    2008-01-01

    Full Text Available Objetivo: Este trabalho teve por objetivo preparar e caracterizar um novo compósito de colágeno com silicato e hidroxiapatita que possa vir a ser utilizado como material endodôntico em capeamento pulpar direto e em pulpotomia. Metodologia: Os materiais utilizados como matéria-prima foram colágeno do tipo I na forma aniônica, silicato (cimento Portland Branco e hidroxiapatita sintetizada. Estes materiais foram misturados em proporções variadas de modo a obter um material compósito na forma de pasta. Os materiais obtidos foram caracterizados por técnicas de calorimetria exploratória diferencial, termogravimetria, microscopia eletrônica de varredura (MEV, espectrometria de dispersão de energia de Raios-X e espectroscopia na região do infravermelho. Resultados: A presença de colágeno no compósito foi demonstrada por transições térmicas típicas daquelas encontradas para o colágeno do tipo I (~48ºC, independentemente da proporção utilizada, e também por imagens de MEV, onde as fibras colagênicas também puderam ser observadas interligando as partículas de silicato. A composição química de todos compósitos de colágeno foi praticamente idêntica à do silicato utilizado. Conclusão: Os resultados mostraram que a estrutura da matriz de colágeno nos compósitos testados não foi alterada. Esta é uma característica importante para a utilização em endodontia do material compósito proposto, objetivando uma reparação tecidual de forma "mais natural"

  7. Impregnação de filmes do compósito de policarbonato (PC e sílicagel (Si com corante fotocrômico em fluido supercrítico = Impregnation of composite from polycarbonate (PC and silica gel (Si films with photochromic dye in supercritical fluid

    Directory of Open Access Journals (Sweden)

    Fernanda de Almeida Fin de Lima

    2010-01-01

    Full Text Available O objetivo deste trabalho foi estudar a impregnação do corante fotocromático Reversacol Graphit® em filmes do compósito de policarbonato (PC e sílica-gel (Si, com a finalidade de obter aplicações em lentes fotocrômicas. Filmes de PC puros também foramimpregnados nas mesmas condições, para verificar o efeito da adição de sílica-gel. Os filmes do compósito foram produzidos em proporções de Si:PC de 1:40 e 1:80 (m m-1, pelo método casting. Para a impregnação do corante Reversacol Graphit nos filmes obtidos foiutilizado o processo supercrítico, pela sua eficiência e benefícios. A impregnação foi feita nos tempos de 15, 30, 45, 60, 90, 120, 150 e 180 min. A temperatura e a pressão adotadas foram de 60ºC e 120 bar. A quantidade de pigmento impregnado nos filmes de Si:PC – 1:40e 1:80 (m m-1 foi de 29 e 23% de massa de corante por massa de compósito, respectivamente, e para o filme de PC puro foi de apenas 2,2% massa de corante por massa de compósito. Pelas análises térmicas, verificou-se que os filmes do compósito apresentarammaior estabilidade térmica. Pela técnica de microscopia eletrônica, observou-se que os filmes de PC puro e dos compósitos Si:PC – 1:40 e 1:80 (m m-1 apresentaram uma superfície lisa e homogênea.The aim of this work was to study the impregnation of the photochromic dye Reversacol Graphit® in composite films ofpolycarbonate (PC and silica gel, with the purpose of finding applications in photochromic lenses. Pure PC films were also impregnated in the same conditions, to verify the effect of the silica-gel addition. The composites films were produced in Si:PC ratios of 1:40 and 1:80 (m m-1, using the casting method . For the impregnation of the dye Reversacol Graphit in the obtained films, the supercritical process was used due to its efficiency and benefits. The impregnation was made in the times of 15, 30, 45, 60, 90, 120, 150 and 180 minutes. The adopted temperature and pressure

  8. Efeito de impactos repetidos de baixa energia em compósitos pultrudados

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    Morais Willy Ank de

    2001-01-01

    Full Text Available Danos internos podem ser gerados em compósitos de matriz polimérica submetidos a impactos de baixa energia. O efeito repetido de eventos desse tipo pode levar, eventualmente, à falha da estrutura. Neste trabalho dois tipos de perfis pultrudados foram submetidos a impactos por queda livre de peso de 0,5 m e 1,0 m de altura. Os resultados obtidos foram analisados em função da disposição das fibras nos perfis e mostram que a existência de uma camada rica em resina em um dos perfis, contribui para reduzir significativamente o desempenho deste perfil. Este comportamento foi associado à formação prematura de trincas na camada rica em resina. O número de eventos de impacto, o tempo de duração de cada choque e a forma da área danificada foram correlacionados com a presença, ou não, da região rica em resina. Os resultados obtidos indicam ainda que a diferença na microestrutura dos perfis analisados é mais significativa para os ensaios de menor energia (queda de 0,5 m. Para os ensaios de maior energia (queda de 1 m a configuração do material teve apenas uma importância secundária.

  9. The transcription factor ETS-1 regulates angiotensin II-stimulated fibronectin production in mesangial cells.

    Science.gov (United States)

    Hua, Ping; Feng, Wenguang; Rezonzew, Gabriel; Chumley, Phillip; Jaimes, Edgar A

    2012-06-01

    Angiotensin II (ANG II) produced as result of activation of the renin-angiotensin system (RAS) plays a critical role in the pathogenesis of chronic kidney disease via its hemodynamic effects on the renal microcirculation as well as by its nonhemodynamic actions including the production of extracellular matrix proteins such as fibronectin, a multifunctional extracellular matrix protein that plays a major role in cell adhesion and migration as well as in the development of glomerulosclerosis. ETS-1 is an important transcription factor essential for normal kidney development and glomerular integrity. We previously showed that ANG II increases ETS-1 expression and is required for fibronectin production in mesangial cells. In these studies, we determined that ANG II induces phosphorylation of ETS-1 via activation of the type 1 ANG II receptor and that Erk1/2 and Akt/PKB phosphorylation are required for these effects. In addition, we characterized the role of ETS-1 on the transcriptional activation of fibronectin production in mesangial cells. We determined that ETS-1 directly activates the fibronectin promoter and by utilizing gel shift assays and chromatin immunoprecipitation assays identified two different ETS-1 binding sites that promote the transcriptional activation of fibronectin in response to ANG II. In addition, we identified the essential role of CREB and its coactivator p300 on the transcriptional activation of fibronectin by ETS-1. These studies unveil novel mechanisms involved in RAS-induced production of the extracellular matrix protein fibronectin in mesangial cells and establish the role of the transcription factor ETS-1 as a direct mediator of these effects.

  10. Identification of intracellular proteins and signaling pathways in human endothelial cells regulated by angiotensin-(1-7).

    Science.gov (United States)

    Meinert, Christian; Gembardt, Florian; Böhme, Ilka; Tetzner, Anja; Wieland, Thomas; Greenberg, Barry; Walther, Thomas

    2016-01-01

    The study aimed to identify proteins regulated by the cardiovascular protective peptide angiotensin-(1-7) and to determine potential intracellular signaling cascades. Human endothelial cells were stimulated with Ang-(1-7) for 1 h, 3 h, 6 h, and 9 h. Peptide effects on intracellular signaling were assessed via antibody microarray, containing antibodies against 725 proteins. Bioinformatics software was used to identify affected intracellular signaling pathways. Microarray data was verified exemplarily by Western blot, Real-Time RT-PCR, and immunohistochemical studies. The microarray identified 110 regulated proteins after 1 h, 119 after 3 h, 31 after 6 h, and 86 after 9 h Ang-(1-7) stimulation. Regulated proteins were associated with high significance to several metabolic pathways like “Molecular Mechanism of Cancer” and “p53 signaling” in a time dependent manner. Exemplarily, Western blots for the E3-type small ubiquitin-like modifier ligase PIAS2 confirmed the microarray data and displayed a decrease by more than 50% after Ang-(1-7) stimulation at 1 h and 3 h without affecting its mRNA. Immunohistochemical studies with PIAS2 in human endothelial cells showed a decrease in cytoplasmic PIAS2 after Ang-(1-7) treatment. The Ang-(1-7) mediated decrease of PIAS2 was reproduced in other endothelial cell types. The results suggest that angiotensin-(1-7) plays a role in metabolic pathways related to cell death and cell survival in human endothelial cells.

  11. Papel de la angiotensina-(1-7 sobre la recaptación neuronal de noradrenalina en la hipertensión

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    Mariela M. Gironacci

    2010-01-01

    Full Text Available RESUMENPreviamente demostramos que la angiotensina (Ang-(1-7, en contraste con la Ang II, disminuyela liberación y la síntesis de noradrenalina (NA en ratas espontáneamentehipertensas (SHR. En el presente trabajo investigamos en ratas SHR el efecto de la Ang-(1-7 sobre la recaptación neuronal y la expresión del transportador de NA (NET, principalresponsable de la eliminación de NA del espacio sináptico. Si bien la Ang-(1-7 no presentaun efecto agudo sobre la recaptación neuronal de noradrenalina, tiene un papel estimuladorsobre el contenido proteico del NET a largo plazo. Esta acción la ejerce a través de laestimulación de la síntesis proteica de novo del transportador por la activación del receptorMas. Esto sugeriría que, a través de la regulación de los niveles de NA en el espacio sináptico,la Ang-(1-7 contribuiría a la regulación de la presión arterial.REV ARGENT CARDIOL 2010;78:151-155.

  12. AT1-receptor mediated vascular damage in myocardium, kidneys and liver in rats Lesão vascular mediada pelo receptor AT1 esses efeitos em miocárdio, rins e fígado de ratos

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    Maria do Carmo Fernandez Vailati

    2010-07-01

    Full Text Available The systemic aspect of vascular damage induced by angiotensin II (ANG II has been poorly explored in the literature. Considering the presence of ANG II and its specific receptor AT1, in several organs, all tissues might be potentially affected by its effects. The aims of this study were: To evaluate the early histological changes in the heart, liver and kidneys, produced by ANG II infusion, to evaluate the protective effect of losartan. Wistar rats were distributed into three groups: control (no treatment, treated with ANG II, and treated with ANG II + losartan. ANG II was continuously infused over 72 hours by subcutaneous osmotic pumps. Histological sections of the myocardium, kidneys and liver were stained and observed for the presence of necrosis. There were ANG II-induced perivascular inflammation and necrosis of the arteriolar wall in the myocardium, kidney, and liver by, which were partially prevented by losartan. There was no significant correlation between heart and kidney damage. Tissue lesion severity was lower than that of vascular lesions, without statistical difference between groups. ANG II causes vascular injury in the heart, kidneys and liver, indicating a systemic vasculotoxic effect; the mechanisms of damage/protection vary depending on the target organ; perivascular lesions may occur even when anti-hypertensive doses of losartan are used.O aspecto sistêmico da lesão vascular induzida pela angiotensina II (ANG II tem sido pouco explorada na literatura. Considerando a presença de ANG II e de seu receptor AT1 em diversos órgãos, todos os tecidos poderiam ser potencialmente afetados por esses efeitos. Os objetivos deste estudo foram: avaliar as alterações histológicas iniciais no coração, fígado e rins, produzidas pela infusão de ANG II, e avaliar o efeito protetor do losartan. Ratos Wistar foram divididos em três grupos: controle (sem tratamento, tratados com ANG II, e tratados com ANG II + losartan. A ANG II foi

  13. ADMA induces monocyte adhesion via activation of chemokine receptors in cultured THP-1 cells.

    Science.gov (United States)

    Chen, Meifang; Li, Yuanjian; Yang, Tianlun; Wang, Yongjin; Bai, Yongping; Xie, Xiumei

    2008-08-01

    Asymmetric dimethylarginine (ADMA), an endogenous NOS inhibitor, is also an important inflammatory factor contributing to the development of atherosclerosis (AS). The present study was to test the effect of ADMA on angiotensin (Ang) II-induced monocytic adhesion. Human monocytoid cells (THP-1) or isolated peripheral blood monocyte cells (PBMCs) were incubated with Ang II (10(-6)M) or exogenous ADMA (30 microM) for 4 or 24h in the absence or presence of losartan or antioxidant PDTC. In cultured THP-1 cells, Ang II (10(-6)M) for 24h elevated the level of ADMA in the medium, upregulated the protein expression of protein arginine methyltransferase (PRMT) and decreased the activity of dimethylarginine dimethylaminohydrolase (DDAH). Both of Ang II and ADMA increased monocytic adhesion to human umbilical vein endothelial cells (HUVECs), elevated the levels of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8 and tumor necrosis factor (TNF)-alpha and upregulated CCR(2) and CXCR(2) mRNA expression, concomitantly with increase in reactive oxygen species (ROS) generation and activation of nuclear factor (NF)-kappaB. Pretreatment with losartan (10 microM) or PDTC (10 microM) abolished the effects mediated by Ang II or ADMA. In isolated PBMCs from healthy individuals, ADMA upregulated the expression of CXCR(2) mRNA, which was attenuated by losartan (10 microM), however, ADMA had no effect on surface protein expression of CCR(2). The present results suggest that ADMA may be involved in monocytic adhesion induced by Ang II via activation of chemokine receptors by ROS/NF-kappaB pathway.

  14. Five years post whiplash injury: Symptoms and psychological factors in recovered versus non-recovered

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    Stålnacke Britt-Marie

    2010-07-01

    Full Text Available Abstract Background Few studies have focused on the differences between persons who are recovered after whiplash injury and those who suffer from persistent disability. The primary aim of this study was therefore to examine differences in symptoms, psychological factors and life satisfaction between subjects classified as recovered and those with persistent disability five years after whiplash injury based on the Neck Disability Index (NDI. Methods A set of questionnaires was answered by 158 persons (75 men, 83 women to assess disability (NDI, pain intensity (VAS, whiplash-related symptoms (Rivermead Post-Concussion Symptoms Questionnaire, RPQ, post-traumatic stress (Impact of Event Scale, IES, depression (Beck's depression inventory, BDI and life satisfaction (LiSat-11. The participants were divided into three groups based on the results of the NDI: recovered (34.8%, mild disability (37.3% and moderate/severe disability (27.3%. Results The moderate/severe group reported significantly higher VAS, BDI and IES scores and lower level of physical health and psychological health compared to the mild and the recovered groups. Less significant differences were reported between the mild and the recovered groups. Conclusions The group with the highest disability score reported most health problems with pain, symptoms, depression, post-traumatic stress and decreased life satisfaction. These findings indicate that classifying these subjects into subgroups based on disability levels makes it possible to optimize the management and treatment after whiplash injury.

  15. Cord Compression due to Extramedullary Hematopoiesis in an Adolescent with Known Beta Thalassemia Major

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    Alan COHLER

    2009-01-01

    Full Text Available We describe a 16 year-old male with ß thalassemia major and gait disturbances that had not been given blood transfusions due to a severe childhood transfusion reaction. Thoracic spine MRI demonstrated hematopoietic marrow throughout the spine and epidural masses causing cord compression consistent with extramedullary hematopoiesis (EMH. After treatment with steroids, radiotherapy and monitored blood transfusions, the patient demonstrated significant improvement of his paraspinal lesions and near complete resolution of his neurological symptoms. While EMH causing cord compression in adolescents is rare in the current era of bone marrow transplantation or chronic transfusions, it should be considered when thalassemia major patients present with neurological deficits. The well defined imaging features of EMH can play a central role in its diagnosis and management, especially because surgical and / or radiotherapeutic intervention are often considered in cases of failed medical treatment.

  16. Dlk1 in normal and abnormal hematopoiesis

    DEFF Research Database (Denmark)

    Sakajiri, S; O'kelly, J; Yin, D

    2005-01-01

    normals. Also, Dlk1 mRNA was elevated in mononuclear, low density bone marrow cells from 11/38 MDS patients, 5/11 AML M6 and 2/4 AML M7 samples. Furthermore, 5/6 erythroleukemia and 2/2 megakaryocytic leukemia cell lines highly expressed Dlk1 mRNA. Levels of Dlk1 mRNA markedly increased during...... (particularly M6, M7), and it appears to be associated with normal development of megakaryocytes and B cells....

  17. Suscetibilidade genética na lesão pulmonar aguda e síndrome da angústia respiratória aguda Genetic susceptibility in acute lung injury and acute respiratory distress syndrome

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    Fernando Suparregui Dias

    2009-12-01

    Full Text Available A lesão pulmonar aguda e sua forma mais grave, a síndrome da angústia respiratória aguda, são o denominador comum de várias doenças que podem provocar uma inflamação exagerada nos pulmões. Nos últimos anos, essa variabilidade tem sido atribuída, pelo menos em parte, a fatores genéticos. O presente estudo tem por objetivos revisar o papel dos principais genes envolvidos na suscetibilidade, morbidade e mortalidade na lesão pulmonar aguda e na síndrome da angústia respiratória aguda. Através de pesquisa nas bases de dados PubMed e LiLACS, empregando-se os unitermos lesão pulmonar aguda, síndrome da angústia respiratória aguda e síndrome da angústia respiratória do adulto em combinação com polimorfismos genéticos, foram selecionados 69 artigos, dos quais 38 foram incluídos nesta revisão. Foram também considerados artigos relevantes extraídos das referências bibliográficas nos artigos selecionados das bases de dados. Os polimorfismos genéticos são variantes gênicas presentes em pelo menos 1% da população. A presença destas variantes genéticas pode influenciar a expressão de mediadores da resposta inflamatória, afetando diretamente a suscetibilidade à lesão pulmonar aguda, a intensidade da inflamação no parênquima pulmonar, a evolução e o desfecho destes pacientes. Estudos de associação com grandes populações e passíveis de reprodução permitirão de modo definitivo a inclusão da genômica no arsenal diagnóstico, prognóstico e terapêutico de pacientes com lesão pulmonar aguda/síndrome da angústia respiratória agudaAcute lung injury and its most severe presentation, acute respiratory distress syndrome, are a common denominator for several diseases which can lead to exaggerated lung inflammation. In the last years this variability has been ascribed, at least partially, to genetic issues. This study aims to review the role of the main genes involved in acute lung injury and acute respiratory

  18. Eugeniusz Misiło, comp. and ed., with an intro. Akcja “Wisła” 1947: Dokumenty i materiały.

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    Jerzy Borzęcki

    2016-02-01

    Full Text Available Eugeniusz Misiło, comp. and ed., with an intro. Akcja “Wisła” 1947: Dokumenty i materiały. Warsaw: Archiwum Ukraińskie and Management Academy Group, 2012. 1246 pp. Illustrations. Maps. Documents section. Appendices section. Biographies sections. Miscellaneous lists. English-language summary. Indexes. Cloth.

  19. Sub-chronic 90-day toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yanli [Department of pharmacology, School of Pharmacy, Huazhong University of Science and Technology, Wuhan 400030 (China); Feng, Yongdong [Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 400030 (China); Li, Yanling [Department of pharmacology, School of Pharmacy, Huazhong University of Science and Technology, Wuhan 400030 (China); Xu, Yiping; Shi, Nian [Department of hygienic toxicology, School of Public Health, Huazhong University of Science and Technology, Wuhan 400030 (China); Hu, Guo-fu [Molecular Oncology Research Institute, Tufts Medical Center, Tufts University, Boston 02111 (United States); Wu, Yunxia, E-mail: wuyunxia@hust.edu.cn [Department of pharmacology, School of Pharmacy, Huazhong University of Science and Technology, Wuhan 400030 (China)

    2017-01-15

    Neamine, an inhibitor of angiogenin (ANG), is a new investigative anticancer drug currently in preclinical stage. Here we report the 90-day sub-chronic toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo. Neamine has a No Observed Adverse Effect Level (NOAEL) of 12 and 16 mg·kg{sup −1}·d{sup −1} for female and male rats, respectively. No mortality was found. The adverse effects included increased organ coefficients of spleen and kidney, increased BUN in both female and male rats at high dose, increased CR and decreased organ coefficients of heart and liver in male rats at high dose. All of which, except the kidney coefficient and BUN in males, returned to normal levels after 28-day recovery. Histopathological examination revealed vacuolar degeneration of glomerulus, degeneration of renal tubules and cast in the kidneys, which were also recovered except in males of high-dosing group. These results indicate that kidney is the most susceptible organ for neamine toxicity. Tissue microarray analysis validated that ANG is up-regulated in hepatocellular carcinoma accompanied by increased nuclear translocation, suggesting that ANG is a possible target for drug development in liver cancer treatment. Neamine blocked nuclear translocation of ANG in HUVEC and HepG2 cells, and inhibited ANG-stimulated cell proliferation without affecting basal level cell proliferation. Neamine also inhibited progression of HepG2 xenografts in athymic mice accompanied by decreased angiogenesis and cancer cell proliferation. These results suggest that neamine is a specific ANG inhibitor with low toxicity and high anti-liver cancer efficacy. - Highlights: • The NOAEL of neamine is 12 mg·kg{sup −1}·d{sup −1} for females and 16 mg·kg{sup −}1·d{sup −1} for males. • The most susceptible organ for neamine toxicity is kidney. • Neamine inhibits the progression of xenograft HepG2 liver cancer in athymic mice.

  20. Sub-chronic 90-day toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo

    International Nuclear Information System (INIS)

    Wu, Yanli; Feng, Yongdong; Li, Yanling; Xu, Yiping; Shi, Nian; Hu, Guo-fu; Wu, Yunxia

    2017-01-01

    Neamine, an inhibitor of angiogenin (ANG), is a new investigative anticancer drug currently in preclinical stage. Here we report the 90-day sub-chronic toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo. Neamine has a No Observed Adverse Effect Level (NOAEL) of 12 and 16 mg·kg −1 ·d −1 for female and male rats, respectively. No mortality was found. The adverse effects included increased organ coefficients of spleen and kidney, increased BUN in both female and male rats at high dose, increased CR and decreased organ coefficients of heart and liver in male rats at high dose. All of which, except the kidney coefficient and BUN in males, returned to normal levels after 28-day recovery. Histopathological examination revealed vacuolar degeneration of glomerulus, degeneration of renal tubules and cast in the kidneys, which were also recovered except in males of high-dosing group. These results indicate that kidney is the most susceptible organ for neamine toxicity. Tissue microarray analysis validated that ANG is up-regulated in hepatocellular carcinoma accompanied by increased nuclear translocation, suggesting that ANG is a possible target for drug development in liver cancer treatment. Neamine blocked nuclear translocation of ANG in HUVEC and HepG2 cells, and inhibited ANG-stimulated cell proliferation without affecting basal level cell proliferation. Neamine also inhibited progression of HepG2 xenografts in athymic mice accompanied by decreased angiogenesis and cancer cell proliferation. These results suggest that neamine is a specific ANG inhibitor with low toxicity and high anti-liver cancer efficacy. - Highlights: • The NOAEL of neamine is 12 mg·kg −1 ·d −1 for females and 16 mg·kg − 1·d −1 for males. • The most susceptible organ for neamine toxicity is kidney. • Neamine inhibits the progression of xenograft HepG2 liver cancer in athymic mice.

  1. Influência da relação estequiométrica resina/endurecedor em propriedades mecânicas de compósitos ternários hierárquicos resina - epóxi/tecido de fibra de carbono/nanotubos de carbono

    Directory of Open Access Journals (Sweden)

    Kássio André Lacerda

    2014-01-01

    Full Text Available A produção de materiais que apresentem alto desempenho em suas aplicações exige avanços tecnológicos e científicos. Os elevados valores de resistência à tração e módulo de elasticidade, aliados à flexibilidade, baixa densidade e alta razão de aspecto, fazem dos nanotubos de carbono excepcionais candidatos para reforçar compósitos poliméricos. Preparamos por laminação sistemas compósitos ternários à base de resina epóxi/tecidos de fibra de carbono (para os binários, acrescendo nanotubos de carbono para os sistemas ternários. Os parâmetros estequiométricos do sistema epoxídico (valor de Phr e concentração de nanotubos de carbono empregado nos sistemas compósitos tiveram avaliadas suas morfologias (MEV, propriedades térmicas (TG e mecânicas (ASTM D790. Embora o sistema epoxídico com Phr 10,0 tenha apresentado uma maior estabilidade térmica, os compósitos ternários produzidos a partir do sistema com Phr 26,6 mostraram valores de tensão máxima e módulo de elasticidade até 8 vezes maiores que aqueles produzidos com o sistema Phr 10. A adição de nanotubos de carbono aos compósitos com Phr 26,6 resultou em ganhos adicionais de aproximadamente 38 e 15% na tensão máxima e no módulo de elasticidade, respectivamente. Esses resultados revelaram a limitação nos métodos de integralização de nanoestruturas a sistemas compósitos, onde as dispersões estão limitadas a uma série de fatores inerentes a interação química e/ou física durante a fabricação dos compósitos nanoestruturados.

  2. Characterization of Angiotensin II Molecular Determinants Involved in AT1 Receptor Functional Selectivity.

    Science.gov (United States)

    Domazet, Ivana; Holleran, Brian J; Richard, Alexandra; Vandenberghe, Camille; Lavigne, Pierre; Escher, Emanuel; Leduc, Richard; Guillemette, Gaétan

    2015-06-01

    The octapeptide angiotensin II (AngII) exerts a variety of cardiovascular effects through the activation of the AngII type 1 receptor (AT1), a G protein-coupled receptor. The AT1 receptor engages and activates several signaling pathways, including heterotrimeric G proteins Gq and G12, as well as the extracellular signal-regulated kinases (ERK) 1/2 pathway. Additionally, following stimulation, βarrestin is recruited to the AT1 receptor, leading to receptor desensitization. It is increasingly recognized that specific ligands selectively bind and favor the activation of some signaling pathways over others, a concept termed ligand bias or functional selectivity. A better understanding of the molecular basis of functional selectivity may lead to the development of better therapeutics with fewer adverse effects. In the present study, we developed assays allowing the measurement of six different signaling modalities of the AT1 receptor. Using a series of AngII peptide analogs that were modified in positions 1, 4, and 8, we sought to better characterize the molecular determinants of AngII that underlie functional selectivity of the AT1 receptor in human embryonic kidney 293 cells. The results reveal that position 1 of AngII does not confer functional selectivity, whereas position 4 confers a bias toward ERK signaling over Gq signaling, and position 8 confers a bias toward βarrestin recruitment over ERK activation and Gq signaling. Interestingly, the analogs modified in position 8 were also partial agonists of the protein kinase C (PKC)-dependent ERK pathway via atypical PKC isoforms PKCζ and PKCι. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  3. Invention de soi et compétences à l’ère des réseaux sociaux

    Directory of Open Access Journals (Sweden)

    Daniel Apollon

    2011-06-01

    Full Text Available Les réseaux sociaux en ligne encouragent de nouvelles approches de la compétence centrées sur la construction biographique de l’individu et l’invention de soi. Ce nouvel art de faire des « produsagers », répond au besoin d’inventer une réponse individuelle et collective au sentiment aliénant de vacuité des sociétés post-industrielles et post-traditionnelles. Combinant opposition et soumission aux éléments structurants et aliénants de cette modernité tardive, ces produsagers réactualisent diverses ruses, tactiques et schèmes immémoriaux déjà explorés par divers auteurs avant Internet. Sur cette toile de fond, l’auteur propose une réinterprétation plus large de la notion de compétence.Social media practices encourage new approaches and visions of competence focusing on the construction of individual biography and the "invention of oneself". The new "artful skills" of "produsers" address the need to invent individual and collective responses to the sense of alienating emptiness pervading postindustrial and posttraditional societies. Combining and submission and opposition to both structuring and alienating aspects of late modernity, these produsagers actualize various tricks, tactics and immemorial schemes already mapped by various authors before the Internet. On this backdrop the author proposes a broader reinterpretation of the concept of competence.

  4. SCIDAC Center for simulation of wave particle interactions CompX participation

    Energy Technology Data Exchange (ETDEWEB)

    Harvey, R.W. [CompX, Del Mar, CA (United States)

    2017-11-14

    Harnessing the energy that is released in fusion reactions would provide a safe and abundant source of power to meet the growing energy needs of the world population. The next step toward the development of fusion as a practical energy source is the construction of ITER, a device capable of producing and controlling the high performance plasma required for self-sustaining fusion reactions, or “burning” plasma. The input power required to drive the ITER plasma into the burning regime will be supplied primarily with a combination of external power from radio frequency waves in the ion cyclotron range of frequencies and energetic ions from neutral beam injection sources, in addition to internally generated Ohmic heating from the induced plasma current that also serves to create the magnetic equilibrium for the discharge. The ITER project is a large multi-billion dollar international project in which the US participates. The success of the ITER project depends critically on the ability to create and maintain burning plasma conditions, it is absolutely necessary to have physics-based models that can accurately simulate the RF processes that affect the dynamical evolution of the ITER discharge. The Center for Simulation of WavePlasma Interactions (CSWPI), also known as RF-SciDAC, is a multi-institutional collaboration that has conducted ongoing research aimed at developing: (1) Coupled core-to-edge simulations that will lead to an increased understanding of parasitic losses of the applied RF power in the boundary plasma between the RF antenna and the core plasma; (2) Development of models for core interactions of RF waves with energetic electrons and ions (including fusion alpha particles and fast neutral beam ions) that include a more accurate representation of the particle dynamics in the combined equilibrium and wave fields; and (3) Development of improved algorithms that will take advantage of massively parallel computing platforms at the petascale level and

  5. Les représentations des enseignants quant à leurs profils de compétences relatives à l’ordinateur : vers une théorie des TIC en éducation

    Directory of Open Access Journals (Sweden)

    François Desjardins

    2005-02-01

    Full Text Available Depuis plusieurs années, dans la littérature, on peut sentir un besoin de préciser l’ensemble de connaissances et de compétences relatives aux ordinateurs nécessaires à l’enseignement et à l’apprentissage. Dans ce contexte, cette recherche vise à développer un modèle global qui permettrait de classer à la fois les outils, leurs usages, leurs incidences ainsi que les connaissances et compétences impliquées dans l’intégration des TIC en éducation de façon à pouvoir comprendre les diverses relations qui existent entre chacune de ces composantes. Une première opérationnalisation de ce modèle a donné lieu au développement d’un instrument permettant de recueillir les représentations des enseignants quant à leurs compétences. Cet article présente le modèle élaboré, le questionnaire qui en a découlé et les résultats des premières analyses statistiques des profils recueillis auprès de plus de 600 enseignants francophones de l’Ontario.

  6. Evaluar la Coordinación Motriz Global en Educación Secundaria: El Test Motor SportComp. [Motor co-ordination assessment in Secondary Education: The SportComp Test].

    Directory of Open Access Journals (Sweden)

    Luis Miguel Ruiz-Perez

    2017-07-01

    Full Text Available El objetivo de este estudio fue el desarrollo y evaluación métrica del Test Motor SportComp, instrumento diseñado para ayudar a los profesores de educación física en la evaluación de la coordinación motriz global de sus alumnos de Educación Secundaria. En la actualidad no existen tests que evalúen la coordinación motriz de forma válida y fiable y que puedan ser empleados por el profesorado de educación física en el contexto de sus clases de manera rápida y económica. El presente test se construyó a partir de una revisión de la literatura científica sobre medición motriz entre los 12 y 17 años. La validez de contenido de las pruebas empleadas fue evaluada por expertos y las pruebas seleccionadas fueron aplicadas a 5732 escolares de estas edades. Se analizaron los resultados mediante la técnica de componentes principales que permitió la extracción de un solo factor formado por 5 tareas motrices relacionadas con la coordinación motriz global. El Coeficiente de Correlación Intraclase (CCI permitió obtener una fiabilidad test-retest de (CCI=0,91. Asimismo, mostró una satisfactoria validez criterial con la batería MABC-2 uno de los más reconocidos para la detección de problemas de coordinación motriz. Las propiedades métricas del presente test son muy satisfactorias y ofrecen buenas posibilidades para ser empleado por los profesores de educación física en sus clases por su bajo coste económico, poco tiempo de aplicación reclamado y poseer normas ajustadas por edad y sexo. Asimismo, este test ofrece el potencial de poder servir para detectar a los alumnos con sospecha de poseer problemas de coordinación motriz y por lo tanto contribuir a la mejora de los programas de educación física que palíen esta condición. Abstract The purpose of this study was the development and metric evaluation of the SportComp Motor Test, an instrument designed to aid physical education teachers in the assessment of gross motor

  7. Crosstalk between TEMs and endothelial cells modulates angiogenesis and metastasis via IGF1-IGF1R signalling in epithelial ovarian cancer.

    Science.gov (United States)

    Wang, Xinjing; Zhu, Qinyi; Lin, Yingying; Wu, Li; Wu, Xiaoli; Wang, Kai; He, Qizhi; Xu, Congjian; Wan, Xiaoping; Wang, Xipeng

    2017-10-24

    Epithelial ovarian cancer (EOC) is the leading cause of death from gynaecologic malignancies and has a poor prognosis due to metastasis. Drugs targeting the angiogenesis pathway significantly improve patient outcome. However, the key factors linking angiogenesis and metastasis have not been elucidated. In this study, we found Tie2 expressing monocytes (CD14 + Tie2 + , TEMs) as key contributors to angiogenesis and metastasis of EOC. Tissue slides were evaluated by immunofluorescence for the presence of total tissue macrophages and TEMs. The correlation between microvascular density (MVD) values and the TEMs number or ratio was calculated in both ovarian cancer tissues and peritoneum. The rate of TEMs in monocytes was evaluated in the peripheral blood of female healthy donors, benign cysts patients, and EOC patients using flow cytometry. The TEMs rate in ascites from EOC patients was also evaluated by flow cytometry. The concentration of Ang2, as the ligand of Tie2, was examined by ELISA in serum samples of EOC patients, benign cysts patients, and ascites samples of EOC patients. The effects of Ang2 on the migration and the cytokine expression of TEMs were further examined. The pro- angiogenesis activity of TEMs via IGF1 was performed in both in vivo and in vitro. And the IGF1 blocking test was performed using neutralising antibody. TEMs were significantly higher in tumour foci, peripheral blood and ascites in EOC patients. The proportion of TEMs among total tissue macrophages was positively correlated with tumour MVD. In vivo animal results showed that TEMs promoted EOC angiogenesis and metastasis. Further functional and mechanisms studies revealed that concentration of angiopoietin 2 (Ang2), a ligand of Tie2, was elevated in EOC ascites which further recruit TEMs in a dose-dependent manner as a powerful chemokine to TEMs. Recruited TEMs promoted endothelial cell function through IGF1-activated downstream signalling. Blocking secreted IGF1 using inhibiting antibody

  8. Fluorine-18 fluorodeoxyglucose splenic uptake from extramedullary hematopoiesis after granulocyte colony-stimulating factor stimulation.

    Science.gov (United States)

    Abdel-Dayem, H M; Rosen, G; El-Zeftawy, H; Naddaf, S; Kumar, M; Atay, S; Cacavio, A

    1999-05-01

    Two patients with sarcoma, one with recurrent osteosarcoma of the spine and the other with metastatic synovial cell sarcoma, were treated with high-dose chemotherapy that produced severe leukopenia. The patients received granulocyte colony-stimulating factor (G-CSF) to stimulate the bone marrow (480 mg given subcutaneously twice daily for 5 to 7 days); their responses were seen as a marked increase in peripheral leukocyte count with no change in the erythrocyte or platelet counts. The patients had fluorine-18 fluorodeoxyglucose (F-18 FDG) imaging 24 hours after the end of G-CSF treatment. Diffusely increased uptake of F-18 FDG was seen in the bone marrow in both patients. In addition, markedly increased uptake in the spleen was noted in both, indicating that the spleen was the site of extramedullary hematopoiesis. The patients had no evidence of splenic metastases. The first patient had a history of irradiation to the dorsal spine, which was less responsive to G-CSF administration than was the nonirradiated lumbar spine.

  9. Single-Cell Network Analysis Identifies DDIT3 as a Nodal Lineage Regulator in Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Cristina Pina

    2015-06-01

    Full Text Available We explore cell heterogeneity during spontaneous and transcription-factor-driven commitment for network inference in hematopoiesis. Since individual genes display discrete OFF states or a distribution of ON levels, we compute and combine pairwise gene associations from binary and continuous components of gene expression in single cells. Ddit3 emerges as a regulatory node with positive linkage to erythroid regulators and negative association with myeloid determinants. Ddit3 loss impairs erythroid colony output from multipotent cells, while forcing Ddit3 in granulo-monocytic progenitors (GMPs enhances self-renewal and impedes differentiation. Network analysis of Ddit3-transduced GMPs reveals uncoupling of myeloid networks and strengthening of erythroid linkages. RNA sequencing suggests that Ddit3 acts through development or stabilization of a precursor upstream of GMPs with inherent Meg-E potential. The enrichment of Gata2 target genes in Ddit3-dependent transcriptional responses suggests that Ddit3 functions in an erythroid transcriptional network nucleated by Gata2.

  10. Angiotensin-converting enzyme 2, Angiotensin-(1-7) and Mas: new players of the Renin Angiotensin System

    DEFF Research Database (Denmark)

    Santos, Robson AS; Ferreira, Anderson J; Verano-Braga, Thiago

    2013-01-01

    /proliferative arm of the RAS consisting of ACE, Ang II and AT1 receptor. In this brief review, we will discuss recent findings related to the biological role of the ACE2/Ang-(1-7)/Mas arm in the cardiovascular and renal systems, as well as in metabolism. In addition, we will highlight the potential interactions...

  11. Dietary sodium deprivation evokes activation of brain regional neurons and down-regulation of angiotensin II type 1 receptor and angiotensin-convertion enzyme mRNA expression.

    Science.gov (United States)

    Lu, B; Yang, X J; Chen, K; Yang, D J; Yan, J Q

    2009-12-15

    Previous studies have indicated that the renin-angiotensin-aldosterone system (RAAS) is implicated in the induction of sodium appetite in rats and that different dietary sodium intakes influence the mRNA expression of central and peripheral RAAS components. To determine whether dietary sodium deprivation activates regional brain neurons related to sodium appetite, and changes their gene expression of RAAS components of rats, the present study examined the c-Fos expression after chronic exposure to low sodium diet, and determined the relationship between plasma and brain angiotensin I (ANG I), angiotensin II (ANG II) and aldosterone (ALD) levels and the sodium ingestive behavior variations, as well as the effects of prolonged dietary sodium deprivation on ANG II type 1 (AT1) and ANG II type 2 (AT2) receptors and angiotensin-convertion enzyme (ACE) mRNA levels in the involved brain regions using the method of real-time polymerase chain reaction (PCR). Results showed that the Fos immunoreactivity (Fos-ir) expression in forebrain areas such as subfornical organ (SFO), paraventricular hypothalamic nuclei (PVN), supraoptic nucleus (SON) and organum vasculosum laminae terminalis (OVLT) all increased significantly and that the levels of ANG I, ANG II and ALD also increased in plasma and forebrain in rats fed with low sodium diet. In contrast, AT1, ACE mRNA in PVN, SON and OVLT decreased significantly in dietary sodium depleted rats, while AT2 mRNA expression did not change in the examined areas. These results suggest that many brain areas are activated by increased levels of plasma and/or brain ANG II and ALD, which underlies the elevated preference for hypertonic salt solution after prolonged exposure to low sodium diet, and that the regional AT1 and ACE mRNA are down-regulated after dietary sodium deprivation, which may be mediated by increased ANG II in plasma and/or brain tissue.

  12. C-X-C motif chemokine 12 influences the development of extramedullary hematopoiesis in the spleens of myelofibrosis patients.

    Science.gov (United States)

    Wang, Xiaoli; Cho, Sool Yeon; Hu, Cing Siang; Chen, Daniel; Roboz, John; Hoffman, Ronald

    2015-02-01

    Myelofibrosis (MF) is characterized by the constitutive mobilization of hematopoietic stem cells (HSC) and hematopoietic progenitor cells (HPC) and the establishment of extramedullary hematopoiesis. The mechanisms underlying this abnormal HSC/HPC trafficking pattern remain poorly understood. We demonstrated that both splenic and peripheral blood (PB) MF CD34(+) cells equally share a defective ability to home to the marrow, but not to the spleens, of NOD/LtSz-Prkdc(scid) mice. This trafficking pattern could not be attributed to discordant expression of integrins or chemokine receptors other than the downregulation of C-X-C chemokine receptor type 4 by both PB and splenic MF CD34(+) cells. The number of both splenic MF CD34(+) cells and HPCs that migrated toward splenic MF plasma was, however, significantly greater than the number that migrated toward PB MF plasma. The concentration of the intact HSC/HPC chemoattractant C-X-C motif chemokine 12 (CXCL12) was greater in splenic MF plasma than PB MF plasma, as quantified using mass spectrometry. Functionally inactive truncated products of CXCL12, which are the product of proteolytic degradation by serine proteases, were detected at similar levels in both splenic and PB MF plasma. Treatment with an anti-CXCL12 neutralizing antibody resulted in a reduction in the degree of migration of splenic MF CD34(+) cells toward both PB and splenic MF plasma, validating the role of CXCL12 as a functional chemoattractant. Our data indicate that the MF splenic microenvironment is characterized by increased levels of intact, functional CXCL12, which contributes to the localization of MF CD34(+) cells to the spleen and the establishment of extramedullary hematopoiesis. Copyright © 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  13. Autosomal dominant cyclic hematopoiesis: Genetics, phenotype, and natural history

    Energy Technology Data Exchange (ETDEWEB)

    Palmer, S.E.; Stephens, K.; Dale, D.C. [Univ. of Washington, Seattle, WA (United States)

    1994-09-01

    Autosomal dominant cyclic hematopoiesis (ADCH; cyclic neutropenia) is a rare disorder manifested by transient neutropenia that recurs every three weeks. To facilitate mapping the ADCH gene by genetic linkage analysis, we studied 9 ADCH families with 42 affected individuals. Pedigrees revealed AD inheritance with no evidence for decreased penetrance. Similar intra- and interfamilial variable expression was observed, with no evidence to support heterogeneity. At least 3 families displayed apparent new mutations. Many adults developed chronic neutropenia, while offspring always cycled during childhood. Children displayed recurrent oral ulcers, gingivitis, lymphadenopathy, fever, and skin and other infections with additional symptoms. Interestingly, there were no cases of neonatal infection. Some children required multiple hospitalizations for treatment. Four males under age 18 died of Clostridium sepsis following necrotizing enterocolitis; all had affected mothers. No other deaths due to ADCH were found; most had improvement of symptoms and infections as adults. Adults experienced increased tooth loss prior to age 30 (16 out of 27 adults, with 9 edentulous). No increase in myelodysplasia, malignancy, or congenital anomalies was observed. Recombinant G-CSF treatment resulted in dramatic improvement of symptoms and infections. The results suggest that ADCH is not a benign disorder, especially in childhood, and abdominal pain requires immediate evaluation. Diagnosis of ADCH requires serial blood counts in the proband and at least one CBC in relatives to exclude similar disorders. Genetic counseling requires specific histories as well as CBCs of each family member at risk to determine status regardless of symptom history, especially to assess apparent new mutations.

  14. Compósitos Bioativos Obtidos a Partir da Inserção de Vidro Bioativo em Matriz de Poli(Metacrilato de Metila Bioactive Composites Obtained from Bioactive Glass Particles into Poly(Methyl Methacrylate

    Directory of Open Access Journals (Sweden)

    Paulo E. Silva Junior

    2001-09-01

    Full Text Available Várias biocerâmicas são capazes de se ligarem a tecidos vivos (bioatividade, no entanto apresentam propriedades mecânicas muito diferentes daquelas exibidas por tecidos naturais. Tal fato acaba por restringir o uso desses materiais em um mais extenso número de aplicações biomédicas. Compósitos de matriz polimérica reforçada com uma fase bioativa podem combinar o comportamento bioativo característico de algumas biocerâmicas com propriedades mecânicas próximas à de tecidos humanos. O presente trabalho tem como objetivo sintetizar e caracterizar compósitos de matriz polimérica reforçada por partículas de vidro bioativo. Os compósitos foram produzidos a partir da polimerização em massa de metacrilato de metila na presença de partículas de vidro bioativo (vidro de silicato de cálcio, fósforo e sódio. Partículas de vidro foram adicionadas ao monômero em diversas concentrações para permitir a variação das propriedades mecânicas e da bioatividade desses compósitos. A bioatividade dos materiais produzidos foi avaliada através de testes in vitro realizados a 37ºC em uma solução simuladora do fluido humano por períodos de tempo de 0 hora a 30 dias. Em seguida, os compósitos submetidos aos testes in vitro foram caracterizados por espectroscopia de infravermelho. O procedimento de síntese mostrou-se eficaz na produção de compósitos com diferentes frações volumétricas de partículas distribuídas homogeneamente pelo material. Os resultados dos testes in vitro revelaram a deposição de uma camada de hidroxiapatita carbonatada (HCA na superfície dos materiais, comprovando a bioatividade dos compósitos. Foi ainda observado que a cinética de deposição da camada de HCA pode ser controlada pela fração volumétrica da fase bioativa.Some bioceramics have the ability to bind to tissues but they show mechanical properties very different from the ones of natural tissues. This fact restricts the use of these

  15. Extramedullary hematopoiesis (EMH) in laboratory animals: offering an insight into stem cell research.

    Science.gov (United States)

    Chiu, Shao-Chih; Liu, Hua-Hsing; Chen, Chia-Ling; Chen, Pin-Ru; Liu, Ming-Chao; Lin, Shinn-Zong; Chang, Ko-Tung

    2015-01-01

    Extramedullary hematopoiesis (EMH) is a pathological process secondary to underlying bone marrow (BM) insufficiency in adults. It is characterized by the emergence of multipotent hematopoietic progenitors scattered around the affected tissue, most likely in the spleen, liver, and lymph node, etc. EMH in patients frequently receives less medical attention and is neglected unless a compressive or obstructive hematopoietic mass appears to endanger the patient's life. However, on a biological basis, EMH reflects the alteration of relationships among hematopoietic stem and progenitor cells (HSPCs) and their original and new microenvironments. The ability of hematopoietic stem cells (HSCs) to mobilize from the bone marrow and to accommodate and function in extramedullary tissues is rather complicated and far from our current understanding. Fortunately, many reports from the studies of drugs and genetics using animals have incidentally found EMH to be involved. Thereby, the molecular basis of EMH could further be elucidated from those animals after cross-comparison. A deeper understanding of the extramedullary hematopoietic niche could help expand stem cells in vitro and establish a better treatment in patients for stem cell transplantation.

  16. Aspirin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription

    International Nuclear Information System (INIS)

    Wang, Xianwei; Lu, Jingjun; Khaidakov, Magomed; Mitra, Sona; Ding, Zufeng; Raina, Sameer; Goyal, Tanu; Mehta, Jawahar L.

    2012-01-01

    Aspirin (acetyl salicylic acid, ASA) is a common drug used for its analgesic and antipyretic effects. Recent studies show that ASA not only blocks cyclooxygenase, but also inhibits NADPH oxidase and resultant reactive oxygen species (ROS) generation, a pathway that underlies pathogenesis of several ailments, including hypertension and tissue remodeling after injury. In these disease states, angiotensin II (Ang II) activates NADPH oxidase via its type 1 receptor (AT1R) and leads to fibroblast growth and collagen synthesis. In this study, we examined if ASA would inhibit NADPH oxidase activation, upregulation of AT1R transcription, and subsequent collagen generation in mouse cardiac fibroblasts challenged with Ang II. Mouse heart fibroblasts were isolated and treated with Ang II with or without ASA. As expected, Ang II induced AT1R expression, and stimulated cardiac fibroblast growth and collagen synthesis. The AT1R blocker losartan attenuated these effects of Ang II. Similarly to losartan, ASA, and its SA moiety suppressed Ang II-mediated AT1R transcription and fibroblast proliferation as well as expression of collagens and MMPs. ASA also suppressed the expression of NADPH oxidase subunits (p22 phox , p47 phox , p67 phox , NOX2 and NOX4) and ROS generation. ASA did not affect total NF-κB p65, but inhibited its phosphorylation and activation. These observations suggest that ASA inhibits Ang II-induced NADPH oxidase expression, NF-κB activation and AT1R transcription in cardiac fibroblasts, and fibroblast proliferation and collagen expression. The critical role of NADPH oxidase activity in stimulation of AT1R transcription became apparent in experiments where ASA also inhibited AT1R transcription in cardiac fibroblasts challenged with H 2 O 2 . Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. -- Highlights: ► Aspirin in therapeutic concentrations decreases mouse cardiac fibroblast growth and collagen

  17. Aspirin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xianwei, E-mail: XWang2@UAMS.edu; Lu, Jingjun; Khaidakov, Magomed; Mitra, Sona; Ding, Zufeng; Raina, Sameer; Goyal, Tanu; Mehta, Jawahar L., E-mail: MehtaJL@UAMS.edu

    2012-03-15

    Aspirin (acetyl salicylic acid, ASA) is a common drug used for its analgesic and antipyretic effects. Recent studies show that ASA not only blocks cyclooxygenase, but also inhibits NADPH oxidase and resultant reactive oxygen species (ROS) generation, a pathway that underlies pathogenesis of several ailments, including hypertension and tissue remodeling after injury. In these disease states, angiotensin II (Ang II) activates NADPH oxidase via its type 1 receptor (AT1R) and leads to fibroblast growth and collagen synthesis. In this study, we examined if ASA would inhibit NADPH oxidase activation, upregulation of AT1R transcription, and subsequent collagen generation in mouse cardiac fibroblasts challenged with Ang II. Mouse heart fibroblasts were isolated and treated with Ang II with or without ASA. As expected, Ang II induced AT1R expression, and stimulated cardiac fibroblast growth and collagen synthesis. The AT1R blocker losartan attenuated these effects of Ang II. Similarly to losartan, ASA, and its SA moiety suppressed Ang II-mediated AT1R transcription and fibroblast proliferation as well as expression of collagens and MMPs. ASA also suppressed the expression of NADPH oxidase subunits (p22{sup phox}, p47{sup phox}, p67{sup phox}, NOX2 and NOX4) and ROS generation. ASA did not affect total NF-κB p65, but inhibited its phosphorylation and activation. These observations suggest that ASA inhibits Ang II-induced NADPH oxidase expression, NF-κB activation and AT1R transcription in cardiac fibroblasts, and fibroblast proliferation and collagen expression. The critical role of NADPH oxidase activity in stimulation of AT1R transcription became apparent in experiments where ASA also inhibited AT1R transcription in cardiac fibroblasts challenged with H{sub 2}O{sub 2}. Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. -- Highlights: ► Aspirin in therapeutic concentrations decreases mouse cardiac

  18. Recovering recyclable materials from shredder residue

    Science.gov (United States)

    Jody, Bassam J.; Daniels, Edward J.; Bonsignore, Patrick V.; Brockmeier, Norman F.

    1994-02-01

    Each year, about 11 million tons of metals are recovered in the United States from about 10 million discarded automobiles. The recovered metals account for about 75 percent of the total weight of the discarded vehicles. The balance of the material, known as shredder residue, amounts to about three million tons annually and is currently landfilled. The residue contains a diversity of potentially recyclable materials, including polyurethane foams, iron oxides, and certain thermoplastics. This article discusses a process under development at Argonne National Laboratory to separate and recover the recyclable materials from this waste stream. The process consists essentially of two stages. First, a physical separation is used to recover the foams and the metal oxides, followed by a chemical process to extract certain thermoplastics. The status of the technology and the process economics are reviewed here.

  19. A persistent cough as atypical clinical presentation of intrathoracic extramedullary hematopoiesis (EMH) in a female with thalassemia intermedia.

    Science.gov (United States)

    Abdulla, Mohammad Aj; Yassin, Mohamed A; Abdelrazek, Mohamed; Mudawi, Deena; Ibrahim, Firyal; Soliman, Dina S; ElOmri, Halima; Nashwan, Abdulqadir J; Fernihough, Liam; De Sanctis, Vincenzo; Soliman, Ashraf T

    2018-02-16

    Extramedullary hematopoiesis (EMH) is a rare disorder, defined as the appearance of hematopoietic elements outside the bone marrow or peripheral blood. The most common sites of EMH are liver and spleen, but it has been documented in other organs such as the mediastinum, lymph nodes, breast, and central nervous system. EMH occurs as a compensatory mechanism for bone marrow dysfunction in severe thalassemia. We report a case of EMH presenting as a posterior mediastinal mass in a 34-year-old woman with thalassemia intermedia with chronic cough and shortness of breath on exertion. The diagnosis of EMH was confirmed by a CT-guided fine needle biopsy. All symptoms disappeared after surgical removal of the mass.

  20. Desenvolvimento de perfis extrudados de compósitos de polietileno de alta densidade com farinha de madeira

    OpenAIRE

    Cristiano Ribeiro de Santi

    2009-01-01

    A extrusão de perfis poliméricos apresenta algumas peculiaridades decorrentes do comportamento de fluxo destes materiais durante o processamento. Por outro lado, o projeto e construção de matrizes para perfis ainda tem sido mais resultado da experiência dos profissionais envolvidos do que um projeto de engenharia na sua essência. Neste trabalho, procurou-se aliar conceitos de engenharia auxiliada por computador ao comportamento reológico de compósitos termoplásticos reforçados com madeira no ...

  1. Targeting metastatic breast cancer with ANG1005, a novel peptide-paclitaxel conjugate that crosses the blood-brain-barrier (BBB

    Directory of Open Access Journals (Sweden)

    Fei Li

    2017-03-01

    Full Text Available We devoted this short interview piece with Dr Shou-Ching Tang at Augusta University to feature some promising results from a clinical phase II trial on a novel brain-penetrating peptide-paclitaxel-conjugate, ANG1005, in treating brain metastatic breast cancer. These results were presented by Dr. Tang at the recent annual meeting of the European Society for Medical Oncology (ESMO 2016 Congress. This development heralds an important step forward towards the development of effective chemotherapeutic agents, which can cross the blood-brain-barrier and effectively treat and prevent the brain metastatic cancers.

  2. Addition of a Nitric Oxide Donor to an Angiotensin II Type 1 Receptor Blocker May Cancel Its Blood Pressure-Lowering Effects.

    Science.gov (United States)

    Yahiro, Eiji; Miura, Shin-Ichiro; Suematsu, Yasunori; Matsuo, Yoshino; Arimura, Tadaaki; Kuwano, Takashi; Imaizumi, Satoshi; Iwata, Atsushi; Uehara, Yoshinari; Saku, Keijiro

    2015-01-01

    While physiological levels of nitric oxide (NO) protect the endothelium and have vasodilatory effects, excessive NO has adverse effects on the cardiovascular system. Recently, new NO-releasing pharmacodynamic hybrids of angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) have been developed.We analyzed whether olmesartan with NO-donor side chains (Olm-NO) was superior to olmesartan (Olm) for the control of blood pressure (BP). Although there was no significant difference in binding affinity to AT1 wild-type (WT) receptor between Olm and Olm-NO in a cell-based binding assay, the suppressive effect of Olm-NO on Ang II-induced inositol phosphate (IP) production was significantly weaker than that of Olm in AT1 WT receptor-expressing cells. While Olm had a strong inverse agonistic effect on IP production, Olm-NO did not. Next, we divided 18 C57BL mice into 3 groups: Ang II (infusion using an osmotic mini-pump) as a control group, Ang II (n = 6) + Olm, and Ang II (n = 6) + Olm-NO groups (n = 6). Olm-NO did not block Ang II-induced high BP after 10 days, whereas Olm significantly decreased BP. In addition, Olm, but not Olm-NO, significantly reduced the ratio of heart weight to body weight (HW/BW) with downregulation of the mRNA levels of atrial natriuretic peptide.An ARB with a NO-donor may cancel BP-lowering effects probably due to excessive NO and a weak blocking effect by Olm-NO toward AT1 receptor activation.

  3. Desenvolvimento e fabrico de compósitos de matriz polimérica com fibras naturais

    OpenAIRE

    Pereira, Júlio Miguel da Cruz Rodrigues

    2017-01-01

    Os compósitos de matriz polimérica com fibras curtas têm propriedades que se têm vindo a relevar como extremamente interessantes para uma ampla variedade de aplicações. Presentemente são fabricados, com recurso a diversas técnicas de processamento, desde componentes específicos para aplicação aeroespacial até artefactos de grande difusão. Estão na agenda mundial, os problemas com a poluição de materiais de origem plástica que fazem uso do petróleo como matéria-prima, a biodegradação destes...

  4. Influence of a pre-treatment with lithium, anabolic agents and hypertransfusion on the regeneration of the hematopoiesis in mice after radiation damage. Einfluss einer Vorbehandlung mit Lithium, Anabolikum und Hypertransfusion auf die Regeneration der Haematopoese bei der Maus nach Strahlenschaden

    Energy Technology Data Exchange (ETDEWEB)

    Bartenstein, P.

    1985-08-27

    In this work it was investigated, whether a week-long pre-treatment with Lithium carbonate, the anabolic agent Deca-Durabolin and syngeneic blood transfusions effected a stimulation, especially of the granulopoiesis, in mice and whether with these measures an increase in the number of pluripotent and myeloically determined stem cells CFUs and CFUc was attained. Further, the question was followed, to what extent these measures have a positive affect on the regeneration of hematopoiesis after radiation damage. Because these therapeutic interventions influence the hematopoiesis through various mechanisms, the detection of eventually present, additive effects should be done using a combination of these types of treatment.

  5. Reforço em compósito de cimento portland através da adição nanotubos de carbono de paredes múltiplas

    Directory of Open Access Journals (Sweden)

    Rogerio Daltro Knuth

    2016-07-01

    Full Text Available A pesquisa desenvolvida no presente trabalho esta embasada na aplicação da nanotecnologia a novos compósitos cimentícios, visando à melhoria das propriedades das argamassas. O objetivo do trabalho foi o de analisar o desempenho físico e mecânico e a ancoragem de uma argamassa de revestimento produzida com nanotubos de carbono de paredes múltiplas (NTCPM, adicionados na quantidade de 0,30% em relação à massa de cimento do compósito, comparativamente ao desempenho com uma argamassa industrializada. Para o presente estudo foi necessário funcionalizar e dispersar os NTCPM, utilizando-se os ácidos sulfúrico (H2SO4 e nítrico (HNO3, e a dispersão foi por ultrassom. Os NTCPM funcionalizados foram neutralizados com hidróxido de amônio (NH3. Foram realizados ensaios de caracterização física e mecânica no estado fresco e no estado endurecido nas argamassas de revestimento com NTCPM e industrializada e análise microestrutura. Os resultados obtidos indicam que a argamassa com NTCPM apresenta melhor desempenho que a argamassa industrializada, no tocante a densidade, consistência, viscosidade, resistência à tração e resistência a compressão axial. Palavras-chave: Argamassas de revestimento. Nanotubos de carbono. Compósitos. Propriedades físicas e mecânicas. Microestrutura.

  6. Cross talk between AT1 receptors and Toll-like receptor 4 in microglia contributes to angiotensin II-derived ROS production in the hypothalamic paraventricular nucleus.

    Science.gov (United States)

    Biancardi, Vinicia Campana; Stranahan, Alexis M; Krause, Eric G; de Kloet, Annette D; Stern, Javier E

    2016-02-01

    ANG II is thought to increase sympathetic outflow by increasing oxidative stress and promoting local inflammation in the paraventricular nucleus (PVN) of the hypothalamus. However, the relative contributions of inflammation and oxidative stress to sympathetic drive remain poorly understood, and the underlying cellular and molecular targets have yet to be examined. ANG II has been shown to enhance Toll-like receptor (TLR)4-mediated signaling on microglia. Thus, in the present study, we aimed to determine whether ANG II-mediated activation of microglial TLR4 signaling is a key molecular target initiating local oxidative stress in the PVN. We found TLR4 and ANG II type 1 (AT1) receptor mRNA expression in hypothalamic microglia, providing molecular evidence for the potential interaction between these two receptors. In hypothalamic slices, ANG II induced microglial activation within the PVN (∼65% increase, P receptors and TLR4 in mediating ANG II-dependent microglial activation and oxidative stress within the PVN. More broadly, our results support a functional interaction between the central renin-angiotensin system and innate immunity in the regulation of neurohumoral outflows from the PVN. Copyright © 2016 the American Physiological Society.

  7. SDN-controlled topology-reconfigurable optical mobile fronthaul architecture for bidirectional CoMP and low latency inter-cell D2D in the 5G mobile era.

    Science.gov (United States)

    Cvijetic, Neda; Tanaka, Akihiro; Kanonakis, Konstantinos; Wang, Ting

    2014-08-25

    We demonstrate the first SDN-controlled optical topology-reconfigurable mobile fronthaul (MFH) architecture for bidirectional coordinated multipoint (CoMP) and low latency inter-cell device-to-device (D2D) connectivity in the 5G mobile networking era. SDN-based OpenFlow control is used to dynamically instantiate the CoMP and inter-cell D2D features as match/action combinations in control plane flow tables of software-defined optical and electrical switching elements. Dynamic re-configurability is thereby introduced into the optical MFH topology, while maintaining back-compatibility with legacy fiber deployments. 10 Gb/s peak rates with <7 μs back-to-back transmission latency and 29.6 dB total power budget are experimentally demonstrated, confirming the attractiveness of the new approach for optical MFH of future 5G mobile systems.

  8. Les compétences infirmières mobilisées dans un service d'oncologie pédiatrique pour répondre aux besoins de l'enfant et sa famille: travail de Bachelor

    OpenAIRE

    Alemanno, Gaëtan; Lorency, Vincent; Morf, Benjamin; Delajoux, Annie

    2013-01-01

    Dans ce travail de bachelor, nous nous intéressons aux compétences infirmières en onco-hématologie pédiatrique. En faisant cette recherche, nous mettons en évidences le vécu des parents dont l’enfant est malade, ainsi que leurs différents besoins ressentis, que ce soit de l’enfant ou des proches aidants. Nous identifions ces compétences en comparant, les actions et pratiques infirmières, avec le modèle de Calgary.

  9. Description of Eucyclops tziscao sp. n., E. angeli sp. n., and a new record of E. festivus Lindberg, 1955 (Cyclopoida, Cyclopidae, Eucyclopinae) in Chiapas, Mexico

    Science.gov (United States)

    Gutiérrez-Aguirre, Martha Angélica; Mercado-Salas, Nancy Fabiola; Cervantes-Martínez, Adrián

    2013-01-01

    Abstract Two new species of the freshwater cyclopoid genera Eucyclops are described, Eucyclops tziscao sp. n. and E. angeli sp. n. Both species belong to the serrulatus-group defined by morphological features such as: the presence of distal spinules or hair-like setae (groups N1 and N2) on frontal surface of antennal basis; the fourth leg coxa with a strong inner spine that bears dense setules on inner side, yet proximally naked (large gap) on outer side; and a 12-segmented antennule with smooth hyaline membrane on the three distalmost segments. Eucyclops tziscao sp. n. is morphologically similar to E. bondi and E. conrowae but differs from these species in having a unique combination of characters, including a caudal ramus 4.05±0.25 times as long as wide, lateral seta of Enp3P4 modified as a strong, sclerotized blunt seta, coxal spine of fourth leg with inner spinule-like setules distally, and sixth leg of males bearing a strong and long inner spine 2.3 times longer than median seta. Eucyclops angeli sp. n. can be distinguished by an unique combination of morphological features: the short caudal ramus; the long spine on the sixth antennular segment of A1; the presence of one additional group of spinules (N12’) on the caudal surface of A2; the presence of long setae in females, or short spinules in males on the lateral margin of fourth prosomite; the strong ornamentation of the intercoxal sclerite of P4, specially group I modified as long denticles; the distal modified setae of Exp3P3 and Exp3P4 in females and males; and the short lateral seta of P5. Finally, we report on a new record of E. festivus in México, and add data on morphology of the species. PMID:24294085

  10. Silicon carbide recovered from photovoltaic industry waste as photocatalysts for hydrogen production

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yu [College of Chemical Engineering, Sichuan University, Chengdu, 610064 (China); Hu, Yu [College of Material Science and Enginneering, Sichuan University, Chengdu, 610064 (China); Zeng, Hongmei [College of Chemistry, Sichuan University, Chengdu, 610064 (China); Zhong, Lin, E-mail: zhonglin@scu.edu.cn [College of Chemical Engineering, Sichuan University, Chengdu, 610064 (China); Liu, Kewei; Cao, Hongmei [College of Chemistry, Sichuan University, Chengdu, 610064 (China); Li, Wei [College of Material Science and Enginneering, Sichuan University, Chengdu, 610064 (China); Yan, Hongjian, E-mail: hjyan@scu.edu.cn [College of Chemistry, Sichuan University, Chengdu, 610064 (China)

    2017-05-05

    Highlights: • SiC was recovered from photovoltaic industry waste. • The recovered SiC is mainly consist of 3C-SiC, 6H-SiC and some silicon oxycarbides. • The recovered SiC shows photocatalytic H{sub 2} evolution from water. - Abstract: In recent years, the focus on creating a dependable and efficient means to recycle or recover the valuable parts from the waste material has drawn significantly attention as an environmentally friendly way to deal with the industrial wastes. The silicon carbide (SiC) crystalline is one of reusable material in the slurry wastes generated during wafer slicing. Here we report the use of recovered SiC from the slurry wastes as photocatalysts to produce hydrogen in the presence of Na{sub 2}SO{sub 3}-Na{sub 2}S as electron donor. The recovered SiC were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy spectra (XPS), UV–vis (UV–vis) spectroscopy, and photoluminescence (PL) spectroscopy. The morphology of SiC loaded with 1 wt% Pt as cocatalyst by thermal-reduction method was observed by scanning electron microscopy (SEM) and high resolution transmission electron microscopy (TEM). The experimental results reveal that the recovered SiC is mainly consist of 3C-SiC, 6H-SiC and some silicon oxycarbides on the surface of the SiC. The highest hydrogen production rate is 191.8 μmol h{sup −1} g{sup −1}. This study provides a way to recycle crystalline SiC from the discharged waste in the photovoltaic industry and reuse it as photocatalyst to yield hydrogen with the advantage of low energy consumption, low pollution and easy operation.

  11. Estudo de propriedades dinâmico-mecânicas de um compósito aeronáutico de CFRP com fios de ligas com memória de forma embebidos

    Directory of Open Access Journals (Sweden)

    Zoroastro Torres Vilar

    2016-01-01

    Full Text Available Resumo Este trabalho trata-se de um estudo experimental do comportamento de propriedades termomecânicas de um compósito ativo, obtido através da introdução de diferentes frações volumétricas de fios de uma liga NiTi com efeito de memoria de forma em uma matriz polimérica reforçada com fibras de carbono (CFRP. Para tal estudo, inicialmente fez-se uma análise do módulo elástico de um pré preg de CFRP aeronáutico com diferentes posições de ângulo de fibras de carbono, a fim de determinar a matriz mais adequada para a introdução de fios de NiTi para obter compósito ativo. Verificou-se que a matriz com fibras alinhadas a 15º apresenta-se como uma boa opção para a obtenção de compósitos ativos, sendo utilizada para a fabricação de amostras de CFRP/NiTi. As amostras tiveram seu potencial de ativação avaliado através da análise da variação do módulo de elasticidade com o aumento da temperatura usando a técnica de Análise Dinâmico-Mecânica (DMA. Através dos resultados obtidos, verificou-se a capacidade de ativação dos compósitos CFRP/NiTi, os quais apresentam variação positiva de módulo de elasticidade ao serem aquecidos acima da temperatura de transformação dos fios NiTi.

  12. [Recovering helpers in the addiction treatment system in Hungary: an interpretative phenomenological analysis].

    Science.gov (United States)

    Kassai, Szilvia; Pintér, Judit Nóra; Rácz, József

    2015-01-01

    The work of recovering helpers who work in the addiction rehabilitation centres was studied. The aim was to investigate the process of addicts becoming recovering helpers, and to study what peer help means to them. According to interpretative phenomenological analysis (IPA) design, subjects were selected, data were collected and analysed. 6 (5 males, 1 female), working as recovering helpers at least one year at addiction rehabilitation centres. Semi-structured life interviews were carried out and analysed according to IPA. Emerging themes from the interviews were identified and summarized, then interpreted as central themes: important periods and turning points of the life story interviews: the experience of psychoactive drugs use, the development of the addiction (which became " Turning Point No 1") then the "rock bottom" experience ("Turning Point No 2"). Then the experience of the helping process was examined: here four major themes were identified: the development of the recovering self and the helping self, the wounded helper and the skilled helper, the experience of the helping process. IPA was found to be a useful method for idiographic exploration of the development and the work of the recovering helpers. The work of the recovering helpers can be described as mentoring of the addict clients. Our experiences might be used for the training programs for recovering helpers as well as to adopt their professional role in addiction services.

  13. Culture, power and identity The case of Ang Hien Hoo, Malang

    Directory of Open Access Journals (Sweden)

    Melani Budianta

    2017-05-01

    Full Text Available This paper discusses the intricate relations between culture and identity in a web of larger power structures of politics and the market by looking at the ways in which the Indonesian Chinese attach themselves to a local performing arts tradition. The paper focuses on the history of the wayang orang amateur club called Ang Hien Hoo in Malang, East Java, which emerged from a Chinese diaspora burial association, to attract national limelight in the 1950s and 1960s. In this paper, I see this amateur club as a site, not only for cultural assimilation, but also as a meeting space for the diverse migrant Chinese population residing at a host country. The space is used to negotiate their position as citizens responsible to promote and to become patrons of local traditional performing arts. The paper examines how this amateur club was swept by the Cold War politics and national political turmoil of 1965, and how it fought to survive under the pressures of the global capitalist era. What emerges from the findings is the contradictory fact that the identification of the Chinese with the Javanese traditional performing arts is affirmed precisely as it is marked by Chineseness. Thus, despite the cultural blending, the Chinese Indonesian’s patronage of local traditional art continuously reproduces the double bind of making home in the culture not seen as their own.

  14. RSCAT_LEVEL_2B_OWV_COMP_12_V1.1:1

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset contains the RapidScat Level 2B 12.5km Version 1.1 science-quality ocean surface wind vectors. The Level 2B wind vectors are binned on a 12.5 km Wind...

  15. Losartan and enalapril decrease viral absorption and interleukin 1 beta production by macrophages in an experimental dengue virus infection.

    Science.gov (United States)

    Hernández-Fonseca, Juan Pablo; Durán, Anyelo; Valero, Nereida; Mosquera, Jesús

    2015-11-01

    The role of angiotensin II (Ang II) in dengue virus infection remains unknown. The aim of this study was to determine the effect of losartan, an antagonist of the angiotensin II type 1 receptor (AT1 receptor), and enalapril, an inhibitor of angiotensin I-converting enzyme (ACE), on viral antigen expression and IL-1β production in peritoneal macrophages infected with dengue virus type 2. Mice treated with losartan or enalapril and untreated controls were infected intraperitoneally with the virus, and macrophages were analyzed. Infection resulted in increased IL-1β production and a high percentage of cells expressing viral antigen, and this was decreased by treatment with anti-Ang II drugs, suggesting a role for Ang II in dengue virus infection.

  16. Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium Excretion.

    Science.gov (United States)

    Sparks, Matthew A; Stegbauer, Johannes; Chen, Daian; Gomez, Jose A; Griffiths, Robert C; Azad, Hooman A; Herrera, Marcela; Gurley, Susan B; Coffman, Thomas M

    2015-12-01

    Inappropriate activation of the type 1A angiotensin (AT1A) receptor contributes to the pathogenesis of hypertension and its associated complications. To define the role for actions of vascular AT1A receptors in BP regulation and hypertension pathogenesis, we generated mice with cell-specific deletion of AT1A receptors in smooth muscle cells (SMKO mice) using Loxp technology and Cre transgenes with robust expression in both conductance and resistance arteries. We found that elimination of AT1A receptors from vascular smooth muscle cells (VSMCs) caused a modest (approximately 7 mmHg) yet significant reduction in baseline BP and exaggerated sodium sensitivity in mice. Additionally, the severity of angiotensin II (Ang II)-dependent hypertension was dramatically attenuated in SMKO mice, and this protection against hypertension was associated with enhanced urinary excretion of sodium. Despite the lower BP, acute vasoconstrictor responses to Ang II in the systemic vasculature were largely preserved (approximately 80% of control levels) in SMKO mice because of exaggerated activity of the sympathetic nervous system rather than residual actions of AT1B receptors. In contrast, Ang II-dependent responses in the renal circulation were almost completely eliminated in SMKO mice (approximately 5%-10% of control levels). These findings suggest that direct actions of AT1A receptors in VSMCs are essential for regulation of renal blood flow by Ang II and highlight the capacity of Ang II-dependent vascular responses in the kidney to effect natriuresis and BP control. Copyright © 2015 by the American Society of Nephrology.

  17. The EPA CompTox Dashboard and Underpinning Software Architecture – a platform for data integration for environmental chemistry data (ACS Fall Meeting 7 of 12)

    Science.gov (United States)

    The CompTox Dashboard was developed by the Environmental Protection Agency’s National Center for Computational Toxicology. This dashboard has been architected in a manner that allows for the deployment of multiple “applications”, both as publicly available databases, and for dep...

  18. Spinal cord compression due to extramedullary hematopoiesis in beta-thalassemia intermedia

    International Nuclear Information System (INIS)

    Munn, Rita K.; Kramer, Carol A.; Arnold, Susanne M.

    1998-01-01

    Background: Extramedullary hematopoiesis (EMH) occurs in many disorders, including thalassemias and other hemoglobinopathies, and commonly presents in the spleen and liver. We present a case of spinal cord compression in a patient with beta-thalassemia intermedia, and review the literature and available treatment options. Patient and Methods: A 35-year-old black female with beta-thalassemia intermedia presented with a 3-week history of back pain and lower extremity weakness. Neurologic examination was consistent with spinal cord compression, and gadolinium enhanced magnetic resonance imaging (MRI) confirmed this diagnosis. She was given intravenous steroids and radiotherapy was begun in 200 cGy fractions to a total dose of 2000 cGy. Results: At the completion of radiotherapy the patient was ambulatory with mild residual weakness. MRI scans 16 months later showed smaller, but persistent masses, and she remains asymptomatic 5 years from her diagnosis. Conclusion: Recognition of spinal cord EMH requires prompt physical examination and MRI for accurate diagnosis. EMH can be managed with radiation, surgery, transfusions, or a combination of these therapies. Radiation in conservative doses of (750-3500 cGy) is non-invasive, avoids the surgical risks of potentially severe hemorrhage and incomplete resection, and has a high complete remission rate in the majority of patients. Relapse rates are moderate (37.5%), but retreatment provides excellent chance for second remission

  19. Influência do método de polimerização na microdureza de compósitos microhíbridos armazenados em água destilada = Influence of curing method on the micro hardness of microhybrid composites immersed in distilled water

    Directory of Open Access Journals (Sweden)

    Herbstrith Segundo, Regênio Mahfuz

    2007-01-01

    Full Text Available O objetivo do presente estudo é comparar e avaliar a microdureza Vickers de um compósito restaurador microhíbrido ativado por dois tipos de unidades polimerizadoras e armazenados em água destilada. Trinta espécimes foram feitos com resina Charisma B1, para cada um dos regimes de polimerização: fotopolimerização por luz halógena, fotopolimerização por LED e fotopolimerização mais ciclo adicional em autoclave. Foram feitas duas leituras de microdureza Vickers por corpo de prova em 1 dia, 7 dias e 14 dias de imersões. O ciclo adicional de polimerização mostrou uma tendência de aumentar os valores de microdureza dos compósitos restauradores, não mostrando diferenças estatisticamente significantes entre LED e Luz Halógena (p > 0,05

  20. Dietary restriction but not angiotensin II type 1 receptor blockade improves DNA damage-related vasodilator dysfunction in rapidly aging Ercc1Δ/- mice.

    Science.gov (United States)

    Wu, Haiyan; van Thiel, Bibi S; Bautista-Niño, Paula K; Reiling, Erwin; Durik, Matej; Leijten, Frank P J; Ridwan, Yanto; Brandt, Renata M C; van Steeg, Harry; Dollé, Martijn E T; Vermeij, Wilbert P; Hoeijmakers, Jan H J; Essers, Jeroen; van der Pluijm, Ingrid; Danser, A H Jan; Roks, Anton J M

    2017-08-01

    DNA damage is an important contributor to endothelial dysfunction and age-related vascular disease. Recently, we demonstrated in a DNA repair-deficient, prematurely aging mouse model ( Ercc1 Δ/- mice) that dietary restriction (DR) strongly increases life- and health span, including ameliorating endothelial dysfunction, by preserving genomic integrity. In this mouse mutant displaying prominent accelerated, age-dependent endothelial dysfunction we investigated the signaling pathways involved in improved endothelium-mediated vasodilation by DR, and explore the potential role of the renin-angiotensin system (RAS). Ercc1 Δ/- mice showed increased blood pressure and decreased aortic relaxations to acetylcholine (ACh) in organ bath experiments. Nitric oxide (NO) signaling and phospho-Ser 1177 -eNOS were compromised in Ercc1 Δ / - DR improved relaxations by increasing prostaglandin-mediated responses. Increase of cyclo-oxygenase 2 and decrease of phosphodiesterase 4B were identified as potential mechanisms. DR also prevented loss of NO signaling in vascular smooth muscle cells and normalized angiotensin II (Ang II) vasoconstrictions, which were increased in Ercc1 Δ/- mice. Ercc1 Δ/ - mutants showed a loss of Ang II type 2 receptor-mediated counter-regulation of Ang II type 1 receptor-induced vasoconstrictions. Chronic losartan treatment effectively decreased blood pressure, but did not improve endothelium-dependent relaxations. This result might relate to the aging-associated loss of treatment efficacy of RAS blockade with respect to endothelial function improvement. In summary, DR effectively prevents endothelium-dependent vasodilator dysfunction by augmenting prostaglandin-mediated responses, whereas chronic Ang II type 1 receptor blockade is ineffective. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  1. Influência da adição de uma carga nanoparticulada no desempenho de compósitos poliuretano/fibra de juta Influence of a nanoparticulate filler addition on the mechanical properties of polyurethane/jute fiber composites

    Directory of Open Access Journals (Sweden)

    José R. A. Neto

    2007-03-01

    Full Text Available Neste trabalho as propriedades mecânicas de um compósito, formado a partir de uma matriz de poliuretano derivado do óleo de mamona e reforçada por um tecido tramado de juta, foram avaliadas. O efeito da adição de pequenos teores de bentonita cálcica e sódica sobre as propriedades mecânicas da matriz de poliuretano e de compósitos poliuretano/juta também foi investigado. Os resultados indicam que a incorporação de fibra de juta à matriz poliuretana promoveu melhora significativa nas propriedades sob tração dos compósitos. A adição de pequenos teores de argila à matriz alterou o desempenho mecânico dos compósitos, porém os resultados não foram os esperados. O compósito híbrido poliuretano/argila/fibra de juta, contudo, apresentou propriedades mecânicas superiores às dos compósitos reforçados unicamente com tecido de juta, o que indica uma atuação sinérgica dos reforços híbridos argila/juta.In this work the mechanical properties of polyurethane/jute fiber composites were evaluated as a function of fiber content and mineral filler addition. A polyurethane (PU derived from castor oil was used as the matrix and hessian cloth as reinforcement. The effect of the incorporation of small amounts of local clay (bentonite, in its calcium and sodium forms, on the mechanical properties of polyurethane/jute composites was also investigated. The results indicate that the tensile properties of the composites substantially increased with jute fiber addition and that although the mechanical properties of the matrix were affected by the addition of nanoparticulate clay, the improvement was not as expected. This was attributed to poor mixing and dispersion of the filler, which was confirmed by SEM. A synergistic effect was observed for the hybrid clay/jute fiber composites, with considerable improvement in the mechanical performance of the hybrid composites.

  2. Extramedullary hematopoiesis of the liver in a child with sickle cell disease: A rare complication.

    Science.gov (United States)

    Barrier, Angela; Willy, Simo; Slone, Jeremy S

    2015-08-01

    We present the case of a 7-year-old Cameroonian girl with sickle cell disease (SCD) who presented with progressive abdominal distension, fever, severe anemia, respiratory distress, and fatigue. Abdominal ultrasound showed a 15.3 cm × 11.5 cm × 15.5 cm solid echogenic mass within the left lobe of the liver. Fine-needle aspiration showed features of extramedullary hematopoiesis (EMH). Despite transfusions, antibiotics, and initiation of hydroxyurea the patient died of respiratory failure during the hospital stay. There is a paucity of information on EMH in the pediatric sickle cell population, especially from resource-limited settings such as western Africa. EMH, however, is a known complication of SCD and should be considered in patients presenting with mass lesions in the setting of chronic anemia. With limited therapeutic interventions for EMH, including radiation and hydroxyurea, the emphasis should be on improving overall treatment of patients with chronic and untreated hemolytic anemia, especially in low-income countries. © 2015 Japan Pediatric Society.

  3. Reduced plasma levels of angiotensin-(1-7 and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

    Directory of Open Access Journals (Sweden)

    E.P. Velloso

    2007-04-01

    Full Text Available The relationship between preeclampsia and the renin-angiotensin system (RAS is poorly understood. Angiotensin I-converting enzyme (ACE is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II and inactivating the vasodilator angiotensin-(1-7 (Ang-(1-7. ACE (I/D polymorphism is characterized by the insertion (I or deletion (D of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D polymorphism was correlated with plasma Ang-(1-7 levels and several RAS components in both preeclamptic (N = 20 and normotensive pregnant women (N = 20. The percentage of the ACE DD genotype (60% in the preeclamptic group was higher than that for the control group (35%; however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260. The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 ± 5.06 vs 27.6 ± 3.25 nmol Hip-His Leu-1 min-1 mL-1 in DD control patients; P = 0.0005. Plasma renin activity was markedly reduced in preeclampsia (0.81 ± 0.2 vs 3.43 ± 0.8 ng Ang I mL plasma-1 h-1 in DD normotensive patients; P = 0.0012. A reduced plasma level of Ang-(1-7 was also observed in preeclamptic women (15.6 ± 1.3 vs 22.7 ± 2.5 pg/mL in the DD control group; P = 0.0146. In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

  4. Reduced plasma levels of angiotensin-(1-7 and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

    Directory of Open Access Journals (Sweden)

    E.P. Velloso

    Full Text Available The relationship between preeclampsia and the renin-angiotensin system (RAS is poorly understood. Angiotensin I-converting enzyme (ACE is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II and inactivating the vasodilator angiotensin-(1-7 (Ang-(1-7. ACE (I/D polymorphism is characterized by the insertion (I or deletion (D of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D polymorphism was correlated with plasma Ang-(1-7 levels and several RAS components in both preeclamptic (N = 20 and normotensive pregnant women (N = 20. The percentage of the ACE DD genotype (60% in the preeclamptic group was higher than that for the control group (35%; however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260. The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 ± 5.06 vs 27.6 ± 3.25 nmol Hip-His Leu-1 min-1 mL-1 in DD control patients; P = 0.0005. Plasma renin activity was markedly reduced in preeclampsia (0.81 ± 0.2 vs 3.43 ± 0.8 ng Ang I mL plasma-1 h-1 in DD normotensive patients; P = 0.0012. A reduced plasma level of Ang-(1-7 was also observed in preeclamptic women (15.6 ± 1.3 vs 22.7 ± 2.5 pg/mL in the DD control group; P = 0.0146. In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

  5. MED, COMP, multilayered and NEIN: an overview of multiple epiphyseal dysplasia

    Energy Technology Data Exchange (ETDEWEB)

    Lachman, Ralph S. [International Skeletal Dysplasia Registry, UCLA School of Medicine, Radiological Services, Department of Pediatrics, Los Angeles, CA (United States); International Skeletal Dysplasia Registry, Los Angeles, CA (United States); Krakow, Deborah; Cohn, Daniel H.; Rimoin, David L. [International Skeletal Dysplasia Registry, UCLA School of Medicine, Radiological Services, Department of Pediatrics, Los Angeles, CA (United States)

    2005-02-01

    This overview covers the group of disorders that presents radiographically as multiple epiphyseal dysplasia (MED). The disorders include ''classic MED'' (Ribbing and Fairbank types): MED that is caused by mutations in the cartilage oligomeric matrix protein (COMP), type IX collagen, and matrilin 3 genes (MATN3); and MED with multilayered patella, brachydactyly, and clubbed feet resultant from mutations in gene defect diastrophic dysplasia (DTDST). The recently identified gene/molecular abnormalities in these disorders have made more exact identification possible in many cases, although clinical testing is not always available. However, there are specific radiographic findings that allow the accurate diagnosis to be made, thus potentially guiding which molecular defect(s) should be investigated. The modes of inheritance of these distinct MED conditions are not identical. When a specific diagnosis is made, proper genetic counseling as well as prognostication, management issues and complications can be delineated to the patient and family. This review will include the mechanics of diagnostic and molecular triage for these disorders. (orig.)

  6. Propostas em ventilação mecânica na síndrome da angústia respiratória

    OpenAIRE

    Auler Junior, José Otávio Costa; Bliacheriene, Fernando; Miyoshi, Erika; Fernandes, Cláudia Regina

    2001-01-01

    JUSTIFICATIVA E OBJETIVOS: O objetivo deste artigo é oferecer ao leitor um resumo das normas já consagradas pela literatura a respeito da estratégia atual do manuseio da ventilação durante a Síndrome da Angústia Respiratória Aguda (SARA). Isto é de fundamental importância, já que a ventilação mecânica, como medida terapêutica, tem estado sob constante revisão e muitos artigos têm sido publicados a este respeito. CONTEÚDO: Este trabalho contém a revisão de 29 artigos e um livro, selecionados a...

  7. Former aux TICE : entre compétences techniques et modèles pédagogiques

    Directory of Open Access Journals (Sweden)

    Jacques Béziat

    2012-01-01

    Full Text Available Cette contribution discute des enjeux et des limites d’une formation aux compétences techniques attendues des futurs enseignants d’école primaire. Une formation est certainement nécessaire pour espérer voir des pratiques pédagogiques avec les TICE se développer en classe. Mais ce n’est qu’un des leviers pour leur intégration dans les pratiques scolaires. Une formation aux TICE suppose que l’on mette l’accent sur l’analyse de pratiques. Plus que de former « simplement » à l’usage pédagogique d’outils numériques, il est indispensable de former à la complexité de leurs enjeux intellectuels et pratiques.

  8. Recovering method for solid waste and facility therefor

    International Nuclear Information System (INIS)

    Omura, Yutaka

    1998-01-01

    When recovering solid wastes in a dry-type storage vessel, a crusher is hoisted down from a cask, and the crusher is operated to crush the solid wastes while holding them. The crushed wastes are temporarily stored at the upper portion of the crusher, and recovered as crushed wastes. In this case, the crusher is turned down, and a shielding vessel is laid the recover downwardly to temporary store the crushed wastes in the shielding vessel. Then, the crusher and the shielding vessel are turned 180deg to contain the crushed wastes into the shielding vessel. With such procedures, the stored solid wastes can be recovered reliably, the stored solid wastes can be reduced in the size, and efficiency of recovering operation can be improved. (T.M.)

  9. Sodium aerosol recovering device

    International Nuclear Information System (INIS)

    Fujimori, Koji; Ueda, Mitsuo; Tanaka, Kazuhisa.

    1997-01-01

    A main body of a recovering device is disposed in a sodium cooled reactor or a sodium cooled test device. Air containing sodium aerosol is sucked into the main body of the recovering device by a recycling fan and introduced to a multi-staged metal mesh filter portion. The air about against each of the metal mesh filters, and the sodium aerosol in the air is collected. The air having a reduced sodium aerosol concentration circulates passing through a recycling fan and pipelines to form a circulation air streams. Sodium aerosol deposited on each of the metal mesh filters is scraped off periodically by a scraper driving device to prevent clogging of each of the metal filters. (I.N.)

  10. Oxidative inhibition of the vascular Na+-K+ pump via NADPH oxidase-dependent β1-subunit glutathionylation: implications for angiotensin II-induced vascular dysfunction.

    Science.gov (United States)

    Liu, Chia-Chi; Karimi Galougahi, Keyvan; Weisbrod, Robert M; Hansen, Thomas; Ravaie, Ramtin; Nunez, Andrea; Liu, Yi B; Fry, Natasha; Garcia, Alvaro; Hamilton, Elisha J; Sweadner, Kathleen J; Cohen, Richard A; Figtree, Gemma A

    2013-12-01

    Glutathionylation of the Na(+)-K(+) pump's β1-subunit is a key molecular mechanism of physiological and pathophysiological pump inhibition in cardiac myocytes. Its contribution to Na(+)-K(+) pump regulation in other tissues is unknown, and cannot be assumed given the dependence on specific β-subunit isoform expression and receptor-coupled pathways. As Na(+)-K(+) pump activity is an important determinant of vascular tone through effects on [Ca(2+)]i, we have examined the role of oxidative regulation of the Na(+)-K(+) pump in mediating angiotensin II (Ang II)-induced increases in vascular reactivity. β1-subunit glutathione adducts were present at baseline and increased by exposure to Ang II in rabbit aortic rings, primary rabbit aortic vascular smooth muscle cells (VSMCs), and human arterial segments. In VSMCs, Ang II-induced glutathionylation was associated with marked reduction in Na(+)-K(+)ATPase activity, an effect that was abolished by the NADPH oxidase inhibitory peptide, tat-gp91ds. In aortic segments, Ang II-induced glutathionylation was associated with decreased K(+)-induced vasorelaxation, a validated index of pump activity. Ang II-induced oxidative inhibition of Na(+)-K(+) ATPase and decrease in K(+)-induced relaxation were reversed by preincubation of VSMCs and rings with recombinant FXYD3 protein that is known to facilitate deglutathionylation of β1-subunit. Knock-out of FXYD1 dramatically decreased K(+)-induced relaxation in a mouse model. Attenuation of Ang II signaling in vivo by captopril (8 mg/kg/day for 7 days) decreased superoxide-sensitive DHE levels in the media of rabbit aorta, decreased β1-subunit glutathionylation, and enhanced K(+)-induced vasorelaxation. Ang II inhibits the Na(+)-K(+) pump in VSMCs via NADPH oxidase-dependent glutathionylation of the pump's β1-subunit, and this newly identified signaling pathway may contribute to altered vascular tone. FXYD proteins reduce oxidative inhibition of the Na(+)-K(+) pump and may have an

  11. Die verband tussen angs en prestasie in takseer sentrumdimensies

    Directory of Open Access Journals (Sweden)

    E. J. Ehlers

    1996-06-01

    Full Text Available The relationship between anxiety and performance in assessment centre dimensions. This study is aimed at determining whether there is a relationship between Anxiety (Tension and Anxiety, as measured by the Sixteen Personality Factor Questionnaire, and performance in assessment centre dimensions. The data set was collected from 145 white male candidates on entry and middle management level in an auditing firm in Gauteng. Ages of candidates varied from 24 to 35 years (x = 27,52; sd = 6,33. By using regression analyses it was found that Tension and Anxiety mainly show a negative relationship with the so-called interpersonal behaviour dimensions, such as Perseverance, Eogical and persuasive reasoning ability, and Perceived leadership image. The multiple analyses of variance (MANOVAS for the low, middle and high tension groups and low, middle and high anxiety groups revealed no statistically significant differences in respect of the assessment centre dimensions as a whole. Implications of the findings are discussed in the article. Opsomming Hierdie studie is daarop toegespits om vas te stel of daar 'n verband tussen Angs (Spanning en Angstigheid, soos deur die Sestien-persoonlikheidsfaktorvraelys gemeet, en prestasie in takseersentrumdimensies bestaan. Data is ingesamel van 145 blanke manlike kandidate op toetrede- en middelbestuursvlak in 'n ouditeursfirma in Gauteng. Ouderdomme van kandidate het gewissel van 24 to 35 jaar (x = 27,52; s = 6,33. Daar is deur middel van regressieontledings bevind dat Spanning en Angstigheid hoofsaaklik 'n negatiewe verband met die sogenaamde interpersoonlike gedragsdimensies, byvoorbeeld Deursettingsverrnoe, Eogiese en oorredende redenasievermoe en Waargeiwme leierskapsbeeld toon. Meervoudige variansieontledings (MANOVAS vir die lae, gemiddelde en hoe spanningsgroepe en die lae, gemiddelde en hoe angstigheidsgroepe hot gcen statisties-beduidende verskille ten opsigte van die takseersentrumdimensies in die geheel

  12. Estudos das propriedades mecânicas e térmicas do polímero biodegradável poli-3-hidroxibutirato (PHB) e de compósitos PHB/pó de madeira.

    OpenAIRE

    Miriam Lúcia Chiquetto Machado

    2008-01-01

    O objetivo deste trabalho foi o estudo das propriedades mecânicas e térmicas do PHB e de compósitos de PHB/pó de madeira processados, reprocessados e irradiados. Foram preparados compósitos com PHB e pó de madeira com concentrações de PHB/pó de madeira de 90/10, 80/20 e 70/30 (m/m). Foram realizados ensaios de propriedades mecânicas, HDT, ponto de amolecimento Vicat, TGA e DSC. A incorporação do pó de madeira aumentou o grau de cristalinidade e a temperatura de cristalização do polímero, e no...

  13. NADPH oxidase 1 deficiency alters caveolin phosphorylation and angiotensin II-receptor localization in vascular smooth muscle.

    Science.gov (United States)

    Basset, Olivier; Deffert, Christine; Foti, Michelangelo; Bedard, Karen; Jaquet, Vincent; Ogier-Denis, Eric; Krause, Karl-Heinz

    2009-10-01

    The superoxide-generating NADPH oxidase NOX1 is thought to be involved in signaling by the angiotensin II-receptor AT1R. However, underlying signaling steps are poorly understood. In this study, we investigated the effect of AngII on aortic smooth muscle from wild-type and NOX1-deficient mice. NOX1-deficient cells showed decreased basal ROS generation and did not produce ROS in response to AngII. Unexpectedly, AngII-dependent Ca(2+) signaling was markedly decreased in NOX1-deficient cells. Immunostaining demonstrated that AT1R was localized on the plasma membrane in wild-type, but intracellularly in NOX1-deficient cells. Immunohistochemistry and immunoblotting showed a decreased expression of AT1R in the aorta of NOX1-deficient mice. To investigate the basis of the abnormal AT1R targeting, we studied caveolin expression and phosphorylation. The amounts of total caveolin and of caveolae were not different in NOX1-deficient mice, but a marked decrease occurred in the phosphorylated form of caveolin. Exogenous H(2)O(2) or transfection of a NOX1 plasmid restored AngII responses in NOX1-deficient cells. Based on these findings, we propose that NOX1-derived reactive oxygen species regulate cell-surface expression of AT1R through mechanisms including caveolin phosphorylation. The lack cell-surface AT1R expression in smooth muscle could be involved in the decreased blood pressure in NOX1-deficient mice.

  14. GeoComp-n, an advanced system for the processing of coarse and medium resolution satellite data. Part 2: biophysical products for Northern ecosystems

    Energy Technology Data Exchange (ETDEWEB)

    Cihlar, J. [Canada Centre for Remote Sensing, Natural Resources Canada, Ottawa, Ontario (Canada); Chen, J. [Canada Centre for Remote Sensing, Natural Resources Canada, Ottawa, Ontario (Canada); Univ. of Toronto, Dept. of Geography, Toronto, Ontario (Canada); Li, Z. [Canada Centre for Remote Sensing, Natural Resources Canada, Ottawa, Ontario (Canada); Univ. of Maryland, Dept of Meteorology, College Park, MD (United States)] [and others

    2002-02-01

    Effective use of satellite data for environmental monitoring requires consistent, high-throughput processing of large volumes of data as it is transformed from raw measurements to useful higher level products. 'GeoComp-n', the next generation of the Geocoding and Compositing System developed at the Canada Centre for Remote Sensing, Natural Resources Canada, was developed as a software solution to this challenge, for use with satellites that provide daily data for the landmass of Canada or comparably large areas. In this paper, the authors discuss the characteristics of the algorithms and methods used in the generation of GeoComp-n products. The theoretical basis and assumptions in the algorithms are described, and the quality of the products is discussed based on validation studies. Examples of a suite of products for Canada during one 10-day period illustrate the diversity and quality of observations for the terrestrial biosphere that may be derived frequently and over large areas from satellites. Issues related to quality assessment in a production environment are also discussed. (author)

  15. GeoComp-n, an advanced system for the processing of coarse and medium resolution satellite data. Part 2: biophysical products for Northern ecosystems

    International Nuclear Information System (INIS)

    Cihlar, J.; Chen, J.; Li, Z.

    2002-01-01

    Effective use of satellite data for environmental monitoring requires consistent, high-throughput processing of large volumes of data as it is transformed from raw measurements to useful higher level products. 'GeoComp-n', the next generation of the Geocoding and Compositing System developed at the Canada Centre for Remote Sensing, Natural Resources Canada, was developed as a software solution to this challenge, for use with satellites that provide daily data for the landmass of Canada or comparably large areas. In this paper, the authors discuss the characteristics of the algorithms and methods used in the generation of GeoComp-n products. The theoretical basis and assumptions in the algorithms are described, and the quality of the products is discussed based on validation studies. Examples of a suite of products for Canada during one 10-day period illustrate the diversity and quality of observations for the terrestrial biosphere that may be derived frequently and over large areas from satellites. Issues related to quality assessment in a production environment are also discussed. (author)

  16. Les effets sur la compétitivité internationale des réglementations relatives à la gestion des effluents d'élevage

    DEFF Research Database (Denmark)

    Andersen, Mikael Skou

    2003-01-01

    différences sensibles de compétitivité de la production porcine et d’une concurrence internationale croissante sur le marché de la viande de porc explique que l’on se préoccupe de la charge financière imposée par les politiques de l’environnement aux éleveurs, notamment en ce qui concerne la gestion des...

  17. Overcoming Endocrine Resistance by Targeting ER/FoxA1/IL 8 Axis

    Science.gov (United States)

    2016-10-01

    Nardone, Carmine De Angelis, Laura M. Heiser , Pavana Anur, Nicholas Wang, Catherine S. Grasso, Paul Spellman, Obi L. Griffith, Anna Tsimelzon...presentations Publications Fu X, Jeselsohn R, Pereira R, Hollingsworth EF, Creighton CJ, Li F, Shea M, Nardone A, Angelis CD, Heiser LM, Anur P, Wang N...performed the bioinformatics analysis of RNA-Seq and ChIP-Seq data. Name: Laura Heiser Project Role: Collaborator Nearest person month worked: 1

  18. An unusual form of spondyloepiphyseal dysplasia, with advanced carpal and spinal end-plate ossification mimicking COMP-mutation-like multiple epiphyseal dysplasia

    Energy Technology Data Exchange (ETDEWEB)

    Pazzaglia, Ugo E.; Zarattini, Guido [University of Brescia Medical School, Department of Orthopaedics and Traumatology, Brescia (Italy); Beluffi, Giampiero [Fondazione IRCCS Policlinico S. Matteo, Section of Paediatric Radiology, Department of Radiodiagnosis, Pavia (Italy)

    2008-07-15

    We present a child with irregular ossification of tubular bone epiphyses, short bones, and spine. The radiographic evolution of bones undergoing endochondral ossification was followed from the age of 1 year 9 months to 6 years. The unusual features demonstrated in this child made classification difficult: pseudoachondroplasia was excluded because no mutations of the COMP gene were found. Considering the evolution of the radiographic appearances, the most likely diagnosis would seem to be an unusual form of spondyloepiphyseal dysplasia, mimicking some aspects of multiple epiphyseal dysplasia. Endochondral ossification was diffusely altered with a mixture of epiphyseal ossification delay associated with acceleration and early fusion. This case was a unique presentation within the family, suggesting a mutation in the affected child. (orig.)

  19. An unusual form of spondyloepiphyseal dysplasia, with advanced carpal and spinal end-plate ossification mimicking COMP-mutation-like multiple epiphyseal dysplasia

    International Nuclear Information System (INIS)

    Pazzaglia, Ugo E.; Zarattini, Guido; Beluffi, Giampiero

    2008-01-01

    We present a child with irregular ossification of tubular bone epiphyses, short bones, and spine. The radiographic evolution of bones undergoing endochondral ossification was followed from the age of 1 year 9 months to 6 years. The unusual features demonstrated in this child made classification difficult: pseudoachondroplasia was excluded because no mutations of the COMP gene were found. Considering the evolution of the radiographic appearances, the most likely diagnosis would seem to be an unusual form of spondyloepiphyseal dysplasia, mimicking some aspects of multiple epiphyseal dysplasia. Endochondral ossification was diffusely altered with a mixture of epiphyseal ossification delay associated with acceleration and early fusion. This case was a unique presentation within the family, suggesting a mutation in the affected child. (orig.)

  20. COMP report: CPQR technical quality control guidelines for low-dose-rate permanent seed brachytherapy.

    Science.gov (United States)

    Beaulieu, Luc; Radford, Dee-Ann; Eduardo Villarreal-Barajas, J

    2018-03-14

    The Canadian Organization of Medical Physicists (COMP), in close partnership with the Canadian Partnership for Quality Radiotherapy (CPQR) has developed a series of Technical Quality Control (TQC) guidelines for radiation treatment equipment. These guidelines outline the performance objectives that equipment should meet in order to ensure an acceptable level of radiation treatment quality. The TQC guidelines have been rigorously reviewed and field tested in a variety of Canadian radiation treatment facilities. The development process enables rapid review and update to keep the guidelines current with changes in technology. This article contains detailed performance objectives and safety criteria for low-dose-rate (LDR) permanent seed brachytherapy. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  1. Les facteurs influançant les compétences des infirmiers et des infirmières en matière de soins spirituels dans un contexte de soins somatiques: une revue de littérature étoffée

    OpenAIRE

    Bédaton, Stéphanie; Hayoz, Marine; Schenevey Perroulaz, Eliane

    2013-01-01

    Les facteurs influençant les compétences des infirmiers et des infirmières en matière de soins spirituels dans un contexte de soins somatiques. Objectif : identifier la place de la spiritualité dans les soins et identifier les facteurs aidants et les obstacles qui influencent les compétences des infirmières dans le domaine de la spiritualité dans un contexte de soins somatiques.

  2. Differential control of MMP and t-PA/PAI-1 expressions by sympathetic and renin-angiotensin systems in rat left ventricle.

    Science.gov (United States)

    Dab, Houcine; Hachani, Rafik; Hodroj, Wassim; Sakly, Mohsen; Bricca, Giampiero; Kacem, Kamel

    2009-10-05

    In the present study, we tested the hypothesis that angiotensin II (Ang II) has both direct (via AT1 receptors) and indirect (via sympathostimulator pathway) actions on the synthesis and activity of the enzymes involved in the extracellular matrix degradation in vivo. For this purpose, sympathectomy and blockade of the Ang II receptor AT1 were performed alone or in combination in normotensive rats. The mRNA of the plasminogen activator (t-PA) and its inhibitor (PAI-1), the mRNA, protein and activity of the matrix metalloproteinases MMP-2 and MMP-9 were examined by Q-RT-PCR, immunoblotting and zymographic methods in the left ventricle. t-PA and PAI-1 mRNA were decreased after sympathectomy and remained unchanged after AT1 receptors blockade. mRNA was increased for t-PA and decreased by similar degree for PAI-1 after double treatment. MMPs mRNA and protein levels were decreased either after sympathectomy or AT1 receptors blockade and an additive effect was acquired after double treatment. MMPs activity was decreased by similar degree in the three treated groups. Deducted interpretations from our experimental approach suggest that Ang II inhibits directly (via AT1 receptors) and indirectly (via sympathostimulator pathway) t-PA mRNA synthesis. It seems unable to influence directly PAI-1 mRNA, but stimulates indirectly PAI-1 mRNA synthesis. Ang II stimulates directly (via AT1 receptors) and indirectly (via sympathostimulator pathway) MMPs synthesis at both transcriptional and protein levels. The enzymatic activity of MMPs does not seem to be influenced directly by Ang II but it could be stimulated indirectly (via sympathostimulator pathway).

  3. Intrathoracic extramedullary hematopoiesis presenting as tumor-simulating lesions of the mediastinum in α-thalassemia: A case report.

    Science.gov (United States)

    An, Jun; Weng, Yimin; He, Jinyuan; Li, Yun; Huang, Shaohong; Cai, Songwang; Zhang, Junhang

    2015-10-01

    Extramedullary hematopoiesis (EMH) is a rare disease, where hematological disorder drives extramedullary hematopoietic tumor formation in multiple regions of the body. The present study reports a case of EMH presenting as multiple tumor-like lesions of mediastinum in a 61-year-old male with α-thalassemia, which was subjected to a video-assisted thoracoscopic surgery tissue biopsy to differentiate it from other mediastinal tumors. To date, only three cases of EMH in patients with α-thalassemia have been described in the literature. Patients with EMH typically exhibit no hematological disorder preoperatively and therefore EMH is frequently misdiagnosed. In the present study, along with a literature review of the clinicopathological features of EMH, the diagnosis and treatment of this rare case was discussed, in order to differentiate diagnosis, and particularly to distinguish EHM from extramedullary myeloid sarcoma.

  4. Adult hematopoietic stem cells lacking Hif-1α self-renew normally

    Science.gov (United States)

    Vukovic, Milica; Sepulveda, Catarina; Subramani, Chithra; Guitart, Amélie V.; Mohr, Jasmine; Allen, Lewis; Panagopoulou, Theano I.; Paris, Jasmin; Lawson, Hannah; Villacreces, Arnaud; Armesilla-Diaz, Alejandro; Gezer, Deniz; Holyoake, Tessa L.; Ratcliffe, Peter J.

    2016-01-01

    The hematopoietic stem cell (HSC) pool is maintained under hypoxic conditions within the bone marrow microenvironment. Cellular responses to hypoxia are largely mediated by the hypoxia-inducible factors, Hif-1 and Hif-2. The oxygen-regulated α subunits of Hif-1 and Hif-2 (namely, Hif-1α and Hif-2α) form dimers with their stably expressed β subunits and control the transcription of downstream hypoxia-responsive genes to facilitate adaptation to low oxygen tension. An initial study concluded that Hif-1α is essential for HSC maintenance, whereby Hif-1α–deficient HSCs lost their ability to self-renew in serial transplantation assays. In another study, we demonstrated that Hif-2α is dispensable for cell-autonomous HSC maintenance, both under steady-state conditions and following transplantation. Given these unexpected findings, we set out to revisit the role of Hif-1α in cell-autonomous HSC functions. Here we demonstrate that inducible acute deletion of Hif-1α has no impact on HSC survival. Notably, unstressed HSCs lacking Hif-1α efficiently self-renew and sustain long-term multilineage hematopoiesis upon serial transplantation. Finally, Hif-1α–deficient HSCs recover normally after hematopoietic injury induced by serial administration of 5-fluorouracil. We therefore conclude that despite the hypoxic nature of the bone marrow microenvironment, Hif-1α is dispensable for cell-autonomous HSC maintenance. PMID:27060169

  5. Pandemic (H1N1 2009 Influenza Virus Infection in A Survivor who has recovered from severe H7N9 Virus Infection, China

    Directory of Open Access Journals (Sweden)

    Shan-Hui Chen

    2016-10-01

    Full Text Available We firstly report a patient who presented with severe complications after infection with influenza A(H1N1 pdm2009, more than one year after recovery from severe H7N9 virus infections. The population of patients who recovered from severe H7N9 infections might be at a higher risk to suffer severe complications after seasonal influenza infections, and they should be included in the high-risk populations recommended to receive seasonal influenza vaccination.

  6. Using semi-automated curation workflows to collect, organize, and curate the data and models necessary to support the EPA CompTox chemical dashboard (ACS Spring meeting)

    Science.gov (United States)

    With the increasing need to leverage data and models to perform cutting edge analyses within the environmental science community, collection and organization of that data into a readily accessible format for consumption is a pressing need. The EPA CompTox chemical dashboard is i...

  7. Using the US EPA's CompTox Dashboard to support identification and screening of emerging organic contaminants in the environment (ACS Spring National meeting) 2 of 7

    Science.gov (United States)

    The US EPA’s iCSS CompTox Dashboard is a curated, publicly accessible resource provided by the National Center for Computational Toxicology (https://comptox.epa.gov). The Dashboard provides support for toxicology and risk assessment within and external to the EPA (including ToxC...

  8. Classe de langue et compétence évaluative des enseignants : entre pratiques évaluatives et politique éducative

    Directory of Open Access Journals (Sweden)

    Mina Sadiqui

    2014-12-01

    Dans une dernière partie nous esquisserons, en nous basant sur une approche didactique, quelques repères qui permettraient à tout enseignant ou futur enseignant de repenser les éléments organisateurs d’un dispositif d’évaluation ,et donc de construire une compétence évaluative en classe de langue, si on veut vraiment mettre en place une nouvelle politique éducative relative à l’enseignement/apprentissage des langues ,en l’occurrence celle du FLE au lycée au Maroc.

  9. Upgraded RECOVER system - CASDAC system

    International Nuclear Information System (INIS)

    Yamamoto, Yoichi; Koyama, Kinji

    1992-03-01

    The CASDAC (Containment And Surveillance Data Authenticated Communication) system has been developed by JAERI for nuclear safeguards and physical protection of nuclear material. This system was designed and constructed as an upgraded RECOVER system, design concept of which was based on the original RECOVER system and also the TRANSEAVER system. Both of them were developed several years ago as a remote monitoring system for continual verification of security and safeguards status of nuclear material. The system consists of two subsystems, one of them is a Grand Command Center (GCC) subsystem and the other is a facility subsystem. Communication between the two subsystems is controlled through the international telephone line network. Therefore all communication data are encrypted to prevent access by an unauthorized person who may intend to make a falsification, or tapping. The facility subsystem has an appropriate measure that ensure data security and reliable operation under unattended mode of operator. The software of this system is designed so as to be easily used in other different types of computers. This report describes the outline of the CASDAC system and the results of its performance test. This work has been carried out in the framework of Japan Support Programme for Agency Safeguards (JASPAS) as a project, JA-1. (author)

  10. Attenuation of myocardial fibrosis with curcumin is mediated by modulating expression of angiotensin II AT1/AT2 receptors and ACE2 in rats

    Directory of Open Access Journals (Sweden)

    Pang XF

    2015-11-01

    Full Text Available Xue-Fen Pang,1 Li-Hui Zhang,2 Feng Bai,1 Ning-Ping Wang,3 Ron E Garner,3 Robert J McKallip,4 Zhi-Qing Zhao1,3 1Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Cardiology, Shanxi Academy of Medical Sciences and Shanxi Dayi Hospital, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Basic Biomedical Sciences, Mercer University School of Medicine, Savannah, GA, USA; 4Division of Basic Biomedical Sciences, Mercer University School of Medicine, Macon, GA, USA Abstract: Curcumin is known to improve cardiac function by balancing degradation and synthesis of collagens after myocardial infarction. This study tested the hypothesis that inhibition of myocardial fibrosis by curcumin is associated with modulating expression of angiotensin II (Ang II receptors and angiotensin-converting enzyme 2 (ACE2. Male Sprague Dawley rats were subjected to Ang II infusion (500 ng/kg/min using osmotic minipumps for 2 and 4 weeks, respectively, and curcumin (150 mg/kg/day was fed by gastric gavage during Ang II infusion. Compared to the animals with Ang II infusion, curcumin significantly decreased the mean arterial blood pressure during the course of the observation. The protein level of the Ang II type 1 (AT1 receptor was reduced, and the Ang II type 2 (AT2 receptor was up-regulated, evidenced by an increased ratio of the AT2 receptor over the AT1 receptor in the curcumin group (1.2±0.02% vs in the Ang II group (0.7±0.03%, P<0.05. These changes were coincident with less locally expressed AT1 receptor and enhanced AT2 receptor in the intracardiac vessels and intermyocardium. Along with these modulations, curcumin significantly decreased the populations of macrophages and alpha smooth muscle actin-expressing myofibroblasts, which were accompanied by reduced expression of transforming growth factor beta 1 and phosphorylated-Smad2/3. Collagen I synthesis was

  11. Industrial recovered-materials-utilization targets for the textile-mill-products industry

    Energy Technology Data Exchange (ETDEWEB)

    None

    1979-01-01

    The Congress, in the National Energy Conservation and Policy Act of 1978 (NECPA), directed the Department of Energy to establish materials recovery targets for the metals and metal products, paper and allied products, rubber, and textile-mill-products industries. The targets were developed to provide incentives for using energy-saving recorded materials and to provied a yardstick for measuring progress and improvement in this endeavor. The NECPA indicates that the targets should represent the maximum technically and economically feasible increase in the use of energy-saving recovered materials that each industry can achieve progressively by January 1, 1987. Materials affected by recovered-materials targets include and are limited to aluminum, copper, lead, zinc, iron, steel, paper and associated products, textile-mill, products, and rubber. Using information gathered from the textile-mill-products industry and from other textile-relaed sources, DOE has developed recovered materials targets for that industry. This report presents those targets and their basis and justification. Following an overview of the textile industry, the chapters are: Textile-Mill-Products Industry Operations; Economic Analysis of the Textile-Mill-Products Industry; Governmental and Regulatory Influence on the US Textile Industry; Current Mill Use of Recovered Materials in the Textile-Mill-Products Industry; Limitations on the Use of Recovered Materials in the US Textile-Mill-Products Industry; Materials-Recovery Targets; and Government and Industry Actions That Could Increase the Use of Recovered Materials.

  12. Ergonomic analysis jobs in recovered factories.

    Science.gov (United States)

    Cuenca, Gabriela; Zotta, Gastón

    2012-01-01

    With the advent of the deep economic crisis in Argentina on 2001, the recovery of companies through to the creation of the Cooperatives Working Self-Management or Factories Recovered by its workers was constituted as one of the ways in which the salaried disobeyed the increasing unemployment. When the companies turn into recovered factories they tend to leave of side practices that have been seen like imposed by the previous organization and not understanding them as a primary condition for the execution of his tasks. Safety and ergonomics are two disciplines that are no longer considered relevant to the daily work. Therefore this investigation aims to revalue, undergo semantic to give back to a place in every organization analyzed. This research developed a self-diagnostic tool for working conditions, and the environment, present in the recovered factories.

  13. Hhex Regulates Hematopoietic Stem Cell Self-Renewal and Stress Hematopoiesis via Repression of Cdkn2a.

    Science.gov (United States)

    Jackson, Jacob T; Shields, Benjamin J; Shi, Wei; Di Rago, Ladina; Metcalf, Donald; Nicola, Nicos A; McCormack, Matthew P

    2017-08-01

    The hematopoietically expressed homeobox transcription factor (Hhex) is important for the maturation of definitive hematopoietic progenitors and B-cells during development. We have recently shown that in adult hematopoiesis, Hhex is dispensable for maintenance of hematopoietic stem cells (HSCs) and myeloid lineages but essential for the commitment of common lymphoid progenitors (CLPs) to lymphoid lineages. Here, we show that during serial bone marrow transplantation, Hhex-deleted HSCs are progressively lost, revealing an intrinsic defect in HSC self-renewal. Moreover, Hhex-deleted mice show markedly impaired hematopoietic recovery following myeloablation, due to a failure of progenitor expansion. In vitro, Hhex-null blast colonies were incapable of replating, implying a specific requirement for Hhex in immature progenitors. Transcriptome analysis of Hhex-null Lin - Sca + Kit + cells showed that Hhex deletion leads to derepression of polycomb repressive complex 2 (PRC2) and PRC1 target genes, including the Cdkn2a locus encoding the tumor suppressors p16 Ink 4 a and p19 Arf . Indeed, loss of Cdkn2a restored the capacity of Hhex-null blast colonies to generate myeloid progenitors in vitro, as well as hematopoietic reconstitution following myeloablation in vivo. Thus, HSCs require Hhex to promote PRC2-mediated Cdkn2a repression to enable continued self-renewal and response to hematopoietic stress. Stem Cells 2017;35:1948-1957. © 2017 AlphaMed Press.

  14. Avaliação da remoção de cromo (III por materiais compósitos porosos adsorventes de PE-g-MA, fibra de coco e quitosana, usando planejamento experimental

    Directory of Open Access Journals (Sweden)

    Dilma Alves Costa

    2017-04-01

    Full Text Available RESUMO Os processos de adsorção podem ser empregados no tratamento de efluentes líquidos contendo metais pesados visando a reduzir os danos ambientais. Porém, o alto custo dos materiais adsorventes justifica a aplicação de adsorventes alternativos, como a fibra de coco (FC e a quitosana (Q. Assim, este trabalho teve como objetivo desenvolver compósitos porosos adsorventes a partir da mistura de polietileno graftizado com anidrido maleico/FC/Q/NaCl, como agente porogênico (PE-g-MA/FC/Q/NaCl, e avaliar estatisticamente a capacidade de adsorção do cromo (III em solução, com auxílio do software Statistica 5.0®. Os resultados mostraram que a eficiência do processo sofreu influência das dimensões da FC, do teor de Q e do pH da solução contendo Cr (III. A capacidade máxima de remoção de Cr (III por unidade de massa do compósito foi de 42,28 mg.g-1.

  15. Leukotriene B4 induces EMT and vimentin expression in PANC-1 pancreatic cancer cells: Involvement of BLT2 via ERK2 activation.

    Science.gov (United States)

    Kim, You Ri; Park, Mi Kyung; Kang, Gyeong Jin; Kim, Hyun Ji; Kim, Eun Ji; Byun, Hyun Jung; Lee, Moo-Yeol; Lee, Chang Hoon

    2016-12-01

    Leukotriene B 4 (LTB 4 ) is a leukocyte chemoattractant and plays a major role controlling inflammatory responses including pancreatitis. LTB 4 is known to be correlated with cancer progression. LTB 4 induces keratin phosphorylation and reorganization by activating extracellular regulated kinase (ERK) in PANC-1 pancreatic cancer cell lines. However, the role of LTB 4 in epithelial mesenchymal transition (EMT) and vimentin expression in pancreatic cancer cells is unknown. We examined whether LTB 4 induces EMT and vimentin expression by Western blot, si-RNA, and RT-PCR. LTB 4 induced morphological change, decreased E-cadherin expression and increased N-cadherin and vimentin expression. LTB4 increased migration and invasion of PANC-1 cancer cells. LTB 4 dose-dependently upregulated expression of vimentin in PANC-1 cancer cells. LTB 4 -induced vimentin expression was suppressed by LY255283 (BLT2 antagonist). Comp A, a BLT2 agonist, further increased vimentin expression. Gene silencing of BLT2 suppressed LTB 4 -or Comp A-induced vimentin expression in PANC-1 cells. The MEK inhibitor, PD98059 suppressed Comp A-induced vimentin expression. Comp A or transfection of plasmid containing BLT2 cDNA (pC BLT2 ) activated ERK, and BLT2 gene silencing suppressed Comp A-induced ERK activation. ERK2 siRNA abrogated Comp A-induced vimentin expression and ERK2 overexpression enhanced vimentin expression. One of well-known cause of ras mutation, cigarette smoke extracts increased BLT2 expression in PANC-1 cancer cells. Taken together, these results suggest that BLT2 is involved in LTB 4 -induced vimentin expression through ERK2 in PANC-1 cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Les pôles de compétitivité : le recours au modèle des clusters ?

    Directory of Open Access Journals (Sweden)

    Jean Bouinot

    2007-03-01

    Full Text Available Introduction : définition d’un cluster En novembre 2004, le gouvernement a lancé un appel d’offre pour structurer des pôles de compétitivité que les praticiens français n’hésitent pas à qualifier de cluster, littéralement un rassemblement du type « bouquet de fleurs ». Pour une définition théorique on peut s’appuyer sur une comparaison avec le modèle du district industriel italien (MDII. Le district est spécialisé dans un produit donné (chaussures de sport à Montebelluna, le leader mondial e...

  17. Metformin improves defective hematopoiesis and delays tumor formation in Fanconi anemia mice.

    Science.gov (United States)

    Zhang, Qing-Shuo; Tang, Weiliang; Deater, Matthew; Phan, Ngoc; Marcogliese, Andrea N; Li, Hui; Al-Dhalimy, Muhsen; Major, Angela; Olson, Susan; Monnat, Raymond J; Grompe, Markus

    2016-12-15

    Fanconi anemia (FA) is an inherited bone marrow failure disorder associated with a high incidence of leukemia and solid tumors. Bone marrow transplantation is currently the only curative therapy for the hematopoietic complications of this disorder. However, long-term morbidity and mortality remain very high, and new therapeutics are badly needed. Here we show that the widely used diabetes drug metformin improves hematopoiesis and delays tumor formation in Fancd2 -/- mice. Metformin is the first compound reported to improve both of these FA phenotypes. Importantly, the beneficial effects are specific to FA mice and are not seen in the wild-type controls. In this preclinical model of FA, metformin outperformed the current standard of care, oxymetholone, by improving peripheral blood counts in Fancd2 -/- mice significantly faster. Metformin increased the size of the hematopoietic stem cell compartment and enhanced quiescence in hematopoietic stem and progenitor cells. In tumor-prone Fancd2 -/- Trp53 +/- mice, metformin delayed the onset of tumors and significantly extended the tumor-free survival time. In addition, we found that metformin and the structurally related compound aminoguanidine reduced DNA damage and ameliorated spontaneous chromosome breakage and radials in human FA patient-derived cells. Our results also indicate that aldehyde detoxification might be one of the mechanisms by which metformin reduces DNA damage in FA cells. © 2016 by The American Society of Hematology.

  18. Regulation of hepatic lipogenesis by the transcription complex Prep1-Pbx1

    OpenAIRE

    Cabaro, Serena

    2011-01-01

    Prep1 is an homeodomain transcription factor belonging to the TALE proteins, including also Pbx1, which plays an essential role in hematopoiesis, organogenesis and development. Prep1 forms transcriptionally active complexes with Pbx1 and regulates the activity of several genes. The Prep1 null mutation leads to embryonic death at a very early stage. Therefore, Prep1 hypomorphic (Prep1i/i) mice have been generated. Prep1 heterozygous (Prep1i/+) mice, which express only 55-57% of protein, have a...

  19. Hybrid palliation for critical systemic outflow obstruction: neither rapid stage 1 Norwood nor comprehensive stage 2 mitigate consequences of early risk factors.

    Science.gov (United States)

    Davies, Ryan R; Radtke, Wolfgang; Bhat, Majeed A; Baffa, Jeanne M; Woodford, Edward; Pizarro, Christian

    2015-01-01

    Hybrid palliation with branch pulmonary artery banding (bPAB) has become increasingly common in the early management of patients with critical left ventricular outflow obstruction. Optimal subsequent surgical palliation remains undefined. We retrospectively reviewed patients undergoing initial bPAB for single ventricle physiology with systemic outflow obstruction (2001-2013, n = 37). Patients were stratified by subsequent surgical palliation: stage 1 Norwood (St1N, n = 14), comprehensive stage 2 (CompSt2, n = 11), and none (n = 12). bPAB was performed at a median of 4 days and 2.7-kg, post-bPAB mortality was increased in patients with aortic atresia (odds ratio [OR] = 3.8, 95% confidence interval [CI] = 0.9-15.8) or birth weight <2 kg (OR = 13.8, 95% CI = 1.4-136.4). Palliation strategy did not affect transplant-free survival through second-stage palliation (St1N: 71.4%, CompSt2: 72.7%, P = .9). Among CompSt2 patients, there was a trend toward poorer survival with aortic atresia (0% vs 80%, P = .09); birth weight <2.5 kg was associated with decreased survival (0% vs 89.0%, P = .01). A trend toward lower survival with low birth weight was evident among St1N patients (<2 kg, OR = 0.1, 95% CI = 0.01-1.9, P = .09). CompSt2 mortality occurred on postoperative days 0 and 1. Mortality following St1N occurred at a median of 38.5 days (range = 23.5-104.5). Among survivors of stage 2 palliation, Fontan completion was performed in the same number of patients in each group (St1N: 6/8, 75%, CompSt2: 6/8, 75%). Both St1N and CompSt2 are viable options for subsequent palliation following initial hybrid procedure. Transplant-free survival and eventual Fontan candidacy are similar between groups. Delaying surgical palliation with the CompSt2 did not mitigate the impact of early risk factors such as low birth weight and aortic atresia. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  20. Bullying: ato esburacado na angústia

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes Soares Ornellas

    2012-04-01

    Full Text Available A noção de afeto está no campo do (desprazer, resultante de uma experiência afetiva de satisfação ou insatisfação, e que se manifesta nas necessidades do sujeito. Pode-se dizer que o afeto envolve a ambivalência de sentimentos, do mais agradável ao mais insuportável, e desempenha um papel estruturante para que o sujeito reencontre sua estrutura psíquica, exercendo uma ação mediadora e decisiva sobre a constituição do sujeito do desejo, orientando o seu projeto de vida, sua profissão, sua opção sexual, etc. Essa ambivalência de afetos deve ser exercitada na educação familiar e escolar, na fala e na escuta que o afeto (desprazeroso tem relevância e parece ser silenciado. O desprazer pode ser escandido pelos sintomas medo, depressão, irritabilidade, ansiedade, humilhação. Assim posto o bullying é também conhecido como a síndrome da humilhação. O objetivo da humilhação é a tentativa de destruição do sujeito; a perda da identificação revela um fantasma, na medida em que própria vítima se sente culpada por sofrer ou por estar sofrendo um ato esburacado porque uma das peças não é encontrada e, em lugar do encaixe, o que se mostra é um buraco, o que provoca a angústia entre quem perde e aquele que ganha. ABSTRACT: The notion of affect is thus in the field of (dis pleasure, resulting from an affective experience of satisfaction or dissatisfaction, and that manifests itself on the needs of the subject. You could say that the affection involves the ambivalence of feelings, the more enjoyable the more unbearable, and plays a structural role for the subject to rediscover his psychic structure, exerting a mediator and decisive action on the constitution of the subject of desire, directing the its design life, your profession, your sexual orientation, etc.. This ambivalence of feelings should be exercised in family education and school, talking and listening that affect (dis pleasure is relevant and appears to be