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Sample records for endothelin-1 induced focal

  1. Endothelin-1-induced focal cerebral ischemia in the growth hormone/IGF-1 deficient Lewis Dwarf rat.

    Science.gov (United States)

    Yan, Han; Mitschelen, Matthew; Toth, Peter; Ashpole, Nicole M; Farley, Julie A; Hodges, Erik L; Warrington, Junie P; Han, Song; Fung, Kar-Ming; Csiszar, Anna; Ungvari, Zoltan; Sonntag, William E

    2014-11-01

    Aging is a major risk factor for cerebrovascular disease. Growth hormone (GH) and its anabolic mediator, insulin-like growth factor (IGF)-1, decrease with advancing age and this decline has been shown to promote vascular dysfunction. In addition, lower GH/IGF-1 levels are associated with higher stroke mortality in humans. These results suggest that decreased GH/IGF-1 level is an important factor in increased risk of cerebrovascular diseases. This study was designed to assess whether GH/IGF-1-deficiency influences the outcome of cerebral ischemia. We found that endothelin-1-induced middle cerebral artery occlusion resulted in a modest but nonsignificant decrease in cerebral infarct size in GH/IGF-1 deficient dw/dw rats compared with control heterozygous littermates and dw/dw rats with early-life GH treatment. Expression of endothelin receptors and endothelin-1-induced constriction of the middle cerebral arteries were similar in the three experimental groups. Interestingly, dw/dw rats exhibited reduced brain edema and less astrocytic infiltration compared with their heterozygous littermates and this effect was reversed by GH-treatment. Because reactive astrocytes are critical for the regulation of poststroke inflammatory processes, maintenance of the blood-brain barrier and neural repair, further studies are warranted to determine the long-term functional consequences of decreased astrocytic activation in GH/IGF-1 deficient animals after cerebral ischemia. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.

  2. Melatonin inhibits endothelin-1 and induces endothelial nitric oxide ...

    African Journals Online (AJOL)

    Although, I/R augmented the endothelin-1 (ET-1) gene expression and the level of big endothelin-1 (big ET-1) in liver tissue, melatonin attenuated these increases. Conversely, non-significant decrease in endothelial nitric oxide synthase (eNOS) mRNA expression in I/R group was significantly elevated by melatonin in ...

  3. Interlimb Dynamic after Unilateral Focal Lesion of the Cervical Dorsal Corticospinal Tract with Endothelin-1

    Directory of Open Access Journals (Sweden)

    Walther A. Carvalho

    2017-10-01

    Full Text Available Handedness is one of the most recognized lateralized behavior in humans. Usually, it is associated with manual superiority regarding performance proficiency. For instance, more than 90% of the human population is considered more skilled with the right hand, which is controlled by the left hemisphere, than with the left. However, during the performance of bimanual tasks, the two hands usually assume asymmetric roles, with one hand acting on objects while the other provides support, stabilizing the object. Traditionally, the role of the two hands is viewed as fixed. However, several studies support an alternate view with flexible assignments for the two hands depending on the task. The supporting role of the hand depends on a closed loop pathway based on proprioceptive inputs from the periphery. The circuit’s efferent arm courses through the dorsal corticospinal tract (dCST in rodents and terminate on spinal cord interneurons which modulate the excitability of motoneurons in the ventral horn. In the present work, we developed an experimental model of unilateral lesion targeting the cervical dCST with microinjections of the vasoconstrictor endothelin-1 (ET-1 to evaluate the degree of flexibility of forelimb assignment during a food manipulation task. Our results show that just 3 days after unilateral corticospinal tract (CST injury in the cervical region, rats display severe motor impairment of the ipsilateral forepaw together with a remarkable reversal of motor assignment between the forelimbs.

  4. Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension

    International Nuclear Information System (INIS)

    Satwiko, Muhammad Gahan; Ikeda, Koji; Nakayama, Kazuhiko; Yagi, Keiko; Hocher, Berthold; Hirata, Ken-ichi; Emoto, Noriaki

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAH. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. - Highlights: • Role of endothelin-1 in pulmonary arterial hypertension (PAH) was investigated. • The endothelin-1 transgenic (ETTG) and wild type (WT) mice were analyzed. • ETTG mice spontaneously developed PAH under normoxia conditions. • SU5416 further aggravated PAH in ETTG mice. • Enhanced endothelin system activity could be a causative factor in

  5. Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Satwiko, Muhammad Gahan [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Ikeda, Koji [Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan); Nakayama, Kazuhiko [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Yagi, Keiko [Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan); Hocher, Berthold [Institute for Nutritional Science, University of Potsdam, Potsdam (Germany); Hirata, Ken-ichi [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Emoto, Noriaki, E-mail: emoto@med.kobe-u.ac.jp [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan)

    2015-09-25

    Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAH. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. - Highlights: • Role of endothelin-1 in pulmonary arterial hypertension (PAH) was investigated. • The endothelin-1 transgenic (ETTG) and wild type (WT) mice were analyzed. • ETTG mice spontaneously developed PAH under normoxia conditions. • SU5416 further aggravated PAH in ETTG mice. • Enhanced endothelin system activity could be a causative factor in

  6. Gestational hypoxia induces preeclampsia-like symptoms via heightened endothelin-1 signaling in pregnant rats.

    Science.gov (United States)

    Zhou, Jianjun; Xiao, Daliao; Hu, Yali; Wang, Zhiqun; Paradis, Alexandra; Mata-Greenwood, Eugenia; Zhang, Lubo

    2013-09-01

    Preeclampsia is a life-threatening pregnancy disorder. However, its pathogenesis remains unclear. We tested the hypothesis that gestational hypoxia induces preeclampsia-like symptoms via heightened endothelin-1 (ET-1) signaling. Time-dated pregnant and nonpregnant rats were divided into normoxic and hypoxic (10.5% O2 from the gestational day 6-21) groups. Chronic hypoxia had no significant effect on blood pressure or proteinuria in nonpregnant rats but significantly increased blood pressure on day 12 (systolic blood pressure, 111.7 ± 6.1 versus 138.5 ± 3.5 mm Hg; P=0.004) and day 20 (systolic blood pressure, 103.4 ± 4.6 versus 125.1 ± 6.1 mm Hg; P=0.02) in pregnant rats and urine protein (μg/μL)/creatinine (nmol/μL) ratio on day 20 (0.10 ± 0.01 versus 0.20 ± 0.04; P=0.04), as compared with the normoxic control group. This was accompanied with asymmetrical fetal growth restriction. Hypoxia resulted in impaired trophoblast invasion and uteroplacental vascular remodeling. In addition, plasma ET-1 levels, as well as the abundance of prepro-ET-1 mRNA, ET-1 type A receptor and angiotensin II type 1 receptor protein in the kidney and placenta were significantly increased in the chronic hypoxic group, as compared with the control animals. Treatment with the ET-1 type A receptor antagonist, BQ123, during the course of hypoxia exposure significantly attenuated the hypoxia-induced hypertension and other preeclampsia-like features. The results demonstrate that chronic hypoxia during gestation induces preeclamptic symptoms in pregnant rats via heightened ET-1 and ET-1 type A receptor-mediated signaling, providing a molecular mechanism linking gestational hypoxia and increased risk of preeclampsia.

  7. Neurosensory changes in a human model of endothelin-1 induced pain: a behavioral study

    NARCIS (Netherlands)

    Hans, Guy; Deseure, Kristof; Robert, Dominique; de Hert, Stefan

    2007-01-01

    Although pain is a frequent feature in patients with cancer, its etiology is still poorly understood. In recent years, endothelin-1 (ET-1) has become a major target molecule in the etiology of cancer pain. In this randomised, double-blind study the effects of intradermal injection of ET-1 on

  8. Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages.

    Science.gov (United States)

    Soldano, Stefano; Pizzorni, Carmen; Paolino, Sabrina; Trombetta, Amelia Chiara; Montagna, Paola; Brizzolara, Renata; Ruaro, Barbara; Sulli, Alberto; Cutolo, Maurizio

    2016-01-01

    Alternatively activated (M2) macrophages are phenotypically characterized by the expression of specific markers, mainly macrophage scavenger receptors (CD204 and CD163) and mannose receptor-1 (CD206), and participate in the fibrotic process by over-producing pro-fibrotic molecules, such as transforming growth factor-beta1 (TGFbeta1) and metalloproteinase (MMP)-9. Endothelin-1 (ET-1) is implicated in the fibrotic process, exerting its pro-fibrotic effects through the interaction with its receptors (ETA and ETB). The study investigated the possible role of ET-1 in inducing the transition from cultured human macrophages into M2 cells. Cultured human monocytes (THP-1 cell line) were activated into macrophages (M0 macrophages) with phorbol myristate acetate and subsequently maintained in growth medium (M0-controls) or treated with either ET-1 (100nM) or interleukin-4 (IL-4, 10ng/mL, M2 inducer) for 72 hours. Similarly, primary cultures of human peripheral blood monocyte (PBM)-derived macrophages obtained from healthy subjects, were maintained in growth medium (untreated cells) or treated with ET-1 or IL-4 for 6 days. Both M0 and PBM-derived macrophages were pre-treated with ET receptor antagonist (ETA/BRA, bosentan 10-5M) for 1 hour before ET-1 stimulation. Protein and gene expression of CD204, CD206, CD163, TGFbeta1 were analysed by immunocytochemistry, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Gene expression of interleukin(IL)-10 and macrophage derived chemokine (CCL-22) was evaluated by qRT-PCR. MMP-9 production was investigated by gel zymography. ET-1 significantly increased the expression of M2 phenotype markers CD204, CD206, CD163, IL-10 and CCL-22, and the production of MMP-9 in both cultures of M0 and PBM-derived macrophages compared to M0-controls and untreated cells. In cultured PBM-derived macrophages, ET-1 increased TGFbeta1 protein and gene expression compared to untreated cells. The ET-1-mediated effects were

  9. Intrahippocampal Injection of Endothelin-1: A New Model of Ischemia-induced Seizures in Immature Rats

    Czech Academy of Sciences Publication Activity Database

    Tsenov, Grygoriy; Máttéffyová, Adéla; Mareš, Pavel; Otáhal, Jakub; Kubová, Hana

    2007-01-01

    Roč. 48, Suppl.5 (2007), s. 7-13 ISSN 0013-9580 R&D Projects: GA MŠk(CZ) LC554; GA ČR(CZ) GA305/06/0713; GA ČR(CZ) GD305/03/H148 Institutional research plan: CEZ:AV0Z50110509 Keywords : endothelin-1 * epileptic seizures * immature rats Subject RIV: ED - Physiology Impact factor: 3.569, year: 2007

  10. Stretch induced endothelin-1 secretion by adult rat astrocytes involves calcium influx via stretch-activated ion channels (SACs)

    International Nuclear Information System (INIS)

    Ostrow, Lyle W.; Suchyna, Thomas M.; Sachs, Frederick

    2011-01-01

    Highlights: → Endothelin-1 expression by adult rat astrocytes correlates with cell proliferation. → Stretch-induced ET-1 is inhibited by GsMtx-4, a specific inhibitor of Ca 2+ permeant SACs. → The less specific SAC inhibitor streptomycin also inhibits ET-1 secretion. → Stretch-induced ET-1 production depends on a calcium influx. → SAC pharmacology may provide a new class of therapeutic agents for CNS pathology. -- Abstract: The expression of endothelins (ETs) and ET-receptors is often upregulated in brain pathology. ET-1, a potent vasoconstrictor, also inhibits the expression of astrocyte glutamate transporters and is mitogenic for astrocytes, glioma cells, neurons, and brain capillary endothelia. We have previously shown that mechanical stress stimulates ET-1 production by adult rat astrocytes. We now show in adult astrocytes that ET-1 production is driven by calcium influx through stretch-activated ion channels (SACs) and the ET-1 production correlates with cell proliferation. Mechanical stimulation using biaxial stretch ( 2+ threshold. This coupling of mechanical stress to the astrocyte endothelin system through SACs has treatment implications, since all pathology deforms the surrounding parenchyma.

  11. Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats.

    Science.gov (United States)

    Caires, A; Fernandes, G S; Leme, A M; Castino, B; Pessoa, E A; Fernandes, S M; Fonseca, C D; Vattimo, M F; Schor, N; Borges, F T

    2017-12-11

    Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

  12. Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats

    Directory of Open Access Journals (Sweden)

    A. Caires

    2017-12-01

    Full Text Available Cyclosporin-A (CsA is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1 receptor blockade with bosentan (BOS and macitentan (MAC antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg or MAC (25 mg/kg by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP, RBF and renal vascular resistance (RVR, and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

  13. Endothelin-1 mediates natriuresis but not polyuria during vitamin D-induced acute hypercalcaemia.

    Science.gov (United States)

    Tokonami, Natsuko; Cheval, Lydie; Monnay, Isabelle; Meurice, Guillaume; Loffing, Johannes; Feraille, Eric; Houillier, Pascal

    2017-04-15

    Hypercalcaemia can occur under various pathological conditions, such as primary hyperparathyroidism, malignancy or granulomatosis, and it induces natriuresis and polyuria in various species via an unknown mechanism. A previous study demonstrated that hypercalcaemia induced by vitamin D in rats increased endothelin (ET)-1 expression in the distal nephron, which suggests the involvement of the ET system in hypercalcaemia-induced effects. In the present study, we demonstrate that, during vitamin D-induced hypercalcaemia, the activation of ET system by increased ET-1 is responsible for natriuresis but not for polyuria. Vitamin D-treated hypercalcaemic mice showed a blunted response to amiloride, suggesting that epithelial sodium channel function is inhibited. We have identified an original pathway that specifically mediates the effects of vitamin D-induced hypercalcaemia on sodium handling in the distal nephron without affecting water handling. Acute hypercalcaemia increases urinary sodium and water excretion; however, the underlying molecular mechanism remains unclear. Because vitamin D-induced hypercalcaemia increases the renal expression of endothelin (ET)-1, we hypothesized that ET-1 mediates the effects of hypercalcaemia on renal sodium and water handling. Hypercalcaemia was induced in 8-week-old, parathyroid hormone-supplemented, male mice by oral administration of dihydrotachysterol (DHT) for 3 days. DHT-treated mice became hypercalcaemic and displayed increased urinary water and sodium excretion compared to controls. mRNA levels of ET-1 and the transcription factors CCAAT-enhancer binding protein β and δ were specifically increased in the distal convoluted tubule and downstream segments in DHT-treated mice. To examine the role of the ET system in hypercalcaemia-induced natriuresis and polyuria, mice were treated with the ET-1 receptor antagonist macitentan, with or without DHT. Mice treated with both macitentan and DHT displayed hypercalcaemia and polyuria

  14. Endothelin-1 Regulation of Exercise-Induced Changes in Flow: Dynamic Regulation of Vascular Tone

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    Robert M. Rapoport

    2017-10-01

    Full Text Available Although endothelin (ET-1 is a highly potent vasoconstrictor with considerable efficacy in numerous vascular beds, the role of endogenous ET-1 in the regulation of vascular tone remains unclear. The perspective that ET-1 plays little role in the on-going regulation of vascular tone at least under physiologic conditions is supported by findings that potential ET-1 constriction is minimized by the release of the vasodilator and ET-1 synthesis inhibitor, nitric oxide (NO. Indeed, ET-1 release and constriction is self-limited by ET-1-induced, endothelial ETB receptor-mediated release of NO. Moreover, even if the balance between ET-1 and NO were reversed as the result of lowered NO activity, as occurs in a number of pathophysiologies associated with endothelial dysfunction, the well-known resistance of ET-1 constriction to reversal (as determined with exogenous ET-1 precludes ET-1 in the dynamic, i.e., moment-to-moment, regulation of vascular tone. On the other hand, and as presently reviewed, findings of ET-1-dependent modulation of organ blood flow with exercise under physiologic conditions demonstrate the dynamic regulation of vascular tone by ET-1. We speculate that this regulation is mediated at least in part through changes in ET-1 synthesis/release caused by pulsatile flow-induced shear stress and NO.

  15. Air pollution alters brain and pituitary endothelin-1 and inducible nitric oxide synthase gene expression.

    Science.gov (United States)

    Thomson, Errol M; Kumarathasan, Prem; Calderón-Garcidueñas, Lilian; Vincent, Renaud

    2007-10-01

    Recent work suggests that air pollution is a risk factor for cerebrovascular and neurodegenerative disease. Effects of inhaled pollutants on the production of vasoactive factors such as endothelin (ET) and nitric oxide (NO) in the brain may be relevant to disease pathogenesis. Inhaled pollutants increase circulating levels of ET-1 and ET-3, and the pituitary is a potential source of plasma ET, but the effects of pollutants on the expression of ET and NO synthase genes in the brain and pituitary are not known. In the present study, Fischer-344 rats were exposed by nose-only inhalation to particles (0, 5, 50mg/m3 EHC-93), ozone (0, 0.4, 0.8 ppm), or combinations of particles and ozone for 4 h. Real-time reverse transcription polymerase chain reaction was used to measure mRNA levels in the cerebral hemisphere and pituitary 0 and 24 h post-exposure. Ozone inhalation significantly increased preproET-1 but decreased preproET-3 mRNAs in the cerebral hemisphere, while increasing mRNA levels of preproET-1, preproET-3, and the ET-converting enzyme (ECE)-1 in the pituitary. Inducible NO synthase (iNOS) was initially decreased in the cerebral hemisphere after ozone inhalation, but increased 24 h post-exposure. Particles decreased tumour necrosis factor (TNF)-alpha mRNA in the cerebral hemisphere, and both particles and ozone decreased TNF-alpha mRNA in the pituitary. Our results show that ozone and particulate matter rapidly modulate the expression of genes involved in key vasoregulatory pathways in the brain and pituitary, substantiating the notion that inhaled pollutants induce cerebrovascular effects.

  16. Effect of radiation-induced heart injury on content of cardiac troponin I and endothelin-1 in SD rats

    International Nuclear Information System (INIS)

    Xu Jiuhong; Gao Yaoming; Zhang Junning; Li Xinli

    2011-01-01

    Objective: To investigate the effect of radiation-induced heart injury (RIHD) on cardiac endothelin-1 (ET-1) and cardiac troponin I (cTnI) in SD rats, and the possibility regarding ET-1 and cTnI as biomarker of RIHD was also explored. Methods: Healthy female SD rats were randomly divided into two groups: the control group (C) and irradiation group (R). The rats in R group were irradiated with linear accelerator at a single dose of 25 Gy. Five milliliters blood was collected from the inferior vena cava on the 5th, 15th, 30th, 60th day after radiation. Blood was centrifuged and serum was collected. Content of ET-1 and cTnI in blood serum were detected by ELISA kits. Results: The content of ET-1 in the R group was always higher than that in the C group (P<0.01) during the whole process, and the difference between two groups had statistical significance only on the 5th day (P<0.01) and 15th day (P<0.05) after radiation. However, the content of cTnI in R group was higher than that in the C group within 30 days after radiation, then decreased, and only on the 15th day (P<0.05) and the 30th day (P<0.01) after radiation, there was statistical difference between two groups. Conclusion: The content of ET-1 and cTnI in blood serum increase obviously after receiving RIHD, so these two indicators can be used as markers to diagnose early RIHD sensitively and specifically. (authors)

  17. Endothelin-1 overexpression exacerbates atherosclerosis and induces aortic aneurysms in apolipoprotein E knockout mice.

    Science.gov (United States)

    Li, Melissa W; Mian, Muhammad Oneeb Rehman; Barhoumi, Tlili; Rehman, Asia; Mann, Koren; Paradis, Pierre; Schiffrin, Ernesto L

    2013-10-01

    Endothelin (ET)-1 plays a role in vascular reactive oxygen species production and inflammation. ET-1 has been implicated in human atherosclerosis and abdominal aortic aneurysm (AAA) development. ET-1 overexpression exacerbates high-fat diet-induced atherosclerosis in apolipoprotein E(-/-) (Apoe(-/-)) mice. ET-1-induced reactive oxygen species and inflammation may contribute to atherosclerosis progression and AAA development. Eight-week-old male wild-type mice, transgenic mice overexpressing ET-1 selectively in endothelium (eET-1), Apoe(-/-) mice, and eET-1/Apoe(-/-) mice were fed high-fat diet for 8 weeks. eET-1/Apoe(-/-) had a 45% reduction in plasma high-density lipoprotein (P<0.05) and presented ≥ 2-fold more aortic atherosclerotic lesions compared with Apoe(-/-) (P<0.01). AAAs were detected only in eET-1/Apoe(-/-) (8/21; P<0.05). Reactive oxygen species production was increased ≥ 2-fold in perivascular fat, media, or atherosclerotic lesions in the ascending aorta and AAAs of eET-1/Apoe(-/-) compared with Apoe(-/-) (P<0.05). Monocyte/macrophage infiltration was enhanced ≥ 2.5-fold in perivascular fat of ascending aorta and AAAs in eET-1/Apoe(-/-) compared with Apoe(-/-) (P<0.05). CD4(+) T cells were detected almost exclusively in perivascular fat (3/6) and atherosclerotic lesions (5/6) in ascending aorta of eET-1/Apoe(-/-) (P<0.05). The percentage of spleen proinflammatory Ly-6C(hi) monocytes was enhanced 26% by ET-1 overexpression in Apoe(-/-) (P<0.05), and matrix metalloproteinase-2 was increased 2-fold in plaques of eET-1/Apoe(-/-) (P<0.05) compared with Apoe(-/-). ET-1 plays a role in progression of atherosclerosis and AAA formation by decreasing high-density lipoprotein, and increasing oxidative stress, inflammatory cell infiltration, and matrix metalloproteinase-2 in perivascular fat, vascular wall, and atherosclerotic lesions.

  18. Hypoxia-inducible factor-1α, vascular endothelial growth factor, inducible nitric oxide synthase, and endothelin-1 expression correlates with angiogenesis in congenital heart disease

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    Hsin-Ling Yin

    2016-07-01

    Full Text Available In Taiwan, the average prevalence of congenital heart disease (CHD is 13.08/1000 live births. Most children with CHD die before the age of 5 years; therefore, identifying treatment methods to extend the life of CHD patients is an important issue in clinical practice. The objective of this study is to evaluate the roles of hypoxia-inducible factor-1α (HIF-1α, vascular endothelial growth factor (VEGF, inducible nitric oxide synthase (iNOS, endothelin-1 (ET-1, and CD34 in CHD autopsy cases in comparison with autopsy cases without CHD. The study included 19 autopsy cases, which were divided into the following four groups: acyanotic CHD (n = 11, cyanotic CHD (n = 3, CHD associated with chromosomal abnormalities (n = 3, and complex CHD (n = 2. Heart specimens obtained from 10 autopsy cases without CHD were included as controls. Our results indicated that high percentages of HIF-1α (100%, VEGF (89.5%, iNOS (78.9%, and ET-1 (84.2% expressions were observed in CHD autopsy cases and this was found to be significant. HIF-1α induced by hypoxia could play a potential role in relating downstream gene expressions in CHD patients. Upregulation of VEGF by HIF-1α could play an important role in triggering angiogenesis to protect myocardial cell survival in a hypoxic microenvironment. Therefore, HIF-1α could be a significant prognosis marker in CHD and be a prospective candidate in the development of target therapy in cardiovascular diseases.

  19. Polyphenol fraction of extra virgin olive oil protects against endothelial dysfunction induced by high glucose and free fatty acids through modulation of nitric oxide and endothelin-1

    Directory of Open Access Journals (Sweden)

    Carolina Emilia Storniolo

    2014-01-01

    Full Text Available Epidemiological and clinical studies have reported that olive oil reduces the incidence of cardiovascular disease. However, the mechanisms involved in this beneficial effect have not been delineated. The endothelium plays an important role in blood pressure regulation through the release of potent vasodilator and vasoconstrictor agents such as nitric oxide (NO and endothelin-1 (ET-1, respectively, events that are disrupted in type 2 diabetes. Extra virgin olive oil contains polyphenols, compounds that exert a biological action on endothelial function. This study analyzes the effects of olive oil polyphenols on endothelial dysfunction using an in vitro model that simulates the conditions of type 2 diabetes. Our findings show that high glucose and linoleic and oleic acids decrease endothelial NO synthase phosphorylation, and consequently intracellular NO levels, and increase ET-1 synthesis by ECV304 cells. These effects may be related to the stimulation of reactive oxygen species production in these experimental conditions. Hydroxytyrosol and the polyphenol extract from extra virgin olive oil partially reversed the above events. Moreover, we observed that high glucose and free fatty acids reduced NO and increased ET-1 levels induced by acetylcholine through the modulation of intracellular calcium concentrations and endothelial NO synthase phosphorylation, events also reverted by hydroxytyrosol and polyphenol extract. Thus, our results suggest a protective effect of olive oil polyphenols on endothelial dysfunction induced by hyperglycemia and free fatty acids.

  20. Polyphenol fraction of extra virgin olive oil protects against endothelial dysfunction induced by high glucose and free fatty acids through modulation of nitric oxide and endothelin-1

    OpenAIRE

    Storniolo, Carolina Emilia; Roselló-Catafau, Joan; Pintó, Xavier; Mitjavila, María Teresa; Moreno, Juan José

    2014-01-01

    © 2014 The Authors. Epidemiological and clinical studies have reported that olive oil reduces the incidence of cardiovascular disease. However, the mechanisms involved in this beneficial effect have not been delineated. The endothelium plays an important role in blood pressure regulation through the release of potent vasodilator and vasoconstrictor agents such as nitric oxide (NO) and endothelin-1 (ET-1), respectively, events that are disrupted in type 2 diabetes. Extra virgin olive oil conta...

  1. Endothelin-1 in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    C. Pizzorni

    2011-09-01

    Full Text Available We evaluated endothelin-1 (ET-1 plasma levels in patients affected by primary Raynaud’s phenomenon (PRP, as well as in patients with systemic sclerosis (SSc and secondary Raynaud’s phenomenon (SRP. Furthermore, ET-1 levels were investigated in SSc patients with different patterns of peripheral microvascular damage, as evaluated by nailfold videocapillaroscopy (NVC. Methods: 23 PRP patients, 67 SSc patients according to ACR criteria, and 23 healthy subjects were enrolled. SSc microvascular involvement was classified in three different patterns (Early, Active, and Late by NVC, as previously described. Results: ET-1 was found significantly higher in both PRP and SRP, when compared with controls (median ±IQR: 3.3±2.8, 2.7±2.2, 2.0±2.2, respectively (p=0.05. No statistically significant difference of ET-1 levels was observed between PRP and SRP patients. ET-1 was found higher in patients with Late NVC pattern, when compared with both Active and Early NVC patterns (median±IQR: 3.4±2.5, 2.4±2.2, 2.5±2.1, respectively, but without statistical significance. Patients with Late NVC pattern showed significantly higher ET-1 plasma levels than controls (p=0.03. No correlation was found between ET-1 levels and disease duration in both groups, as well as between ET-1 levels and age of patients. Conclusions: These data support previous studies, reporting increased ET-1 plasma levels in both PRP and SRP patients. Interestingly, patients with the Late NVC pattern of microangiopathy showed higher ET-1 plasma levels than controls. The high levels of ET-1 detected in the Late NVC pattern of microangiopathy might be related to the larger fibrotic involvement typical of the advanced stages of disease.

  2. Estrogen-induced improvement in coronary flow responses during atrial pacing in relation to endothelin-1 levels in postmenopausal women without coronary disease

    Directory of Open Access Journals (Sweden)

    Ioannis Kallikazaros

    2008-06-01

    Full Text Available Ioannis Kallikazaros, Costas Tsioufis, Panagiotis Zambaras, Ioannis Skiadas, Marina Toutouza, Dimitrios Tousoulis, Christodoulos Stefanadis, Pavlos ToutouzasCardiology Department and University Cardiology Clinic, Hippokration Hospital of Athens, GreeceBackground: The cardioprotective role of hormonal replacement therapy remains in doubt, but interest is increasing in the vascular effects of estrogens especially in coronary circulation.Methods: Coronary blood flow (CBF was measured in 24 postmenopausal women (age 55 ± 3 years, whose coronary arteries appeared angiographically normal, during incremental atrial pacing (AP before and 20 minutes after intracoronary administration of either 75 ng/mL 17-β estradiol (treated group, n = 18 or 0.9% saline (controls, n = 6.Results: Before estrogen, no differences in the coronary vasomotor responses at AP between the two groups (p = NS could be detected. After estrogen, in the treated group, at the peak of the second AP, the coronary artery diameter decreased by 0.17 mm (p < 0.005 while the CBF increased by 61 mL/min (p < 0.05. These changes differed significantly from thoseobserved at the peak of first AP (p < 0.001 for both cases. In contrast, in the control group no such changes were observed. The endothelin-1 (ET-1 levels in the coronary sinus were significantly reduced after estrogen infusion, which was negatively correlated with the degree of coronary artery constriction (r = −0.40, p = 0.03 and positively correlated with the increase in CBF (r = 0.54, p = 0.01.Conclusions: In postmenopausal women without coronary artery disease, the intracoronary estrogen infusion mediates a greater increase in CBF and is positively correlated with the reduction of the coronary sinus ET-1 levels at the peak of AP.Keywords: estrogens, coronary blood flow, endothelin-1, coronary interventions

  3. Vascular mechanism of action of endothelin-1: Effect of Ca2+ antagonists

    International Nuclear Information System (INIS)

    Chabrier, P.E.; Auguet, M.; Roubert, P.; Lonchampt, M.O.; Gillard, V.; Guillon, J.M.; Delaflotte, S.; Braquet, P.

    1989-01-01

    The vasoconstrictive properties of the endothelium-derived peptide, endothelin-1 (ET-1), were investigated on rat isolated aorta and on cultured rat aortic smooth muscle cells. In rat isolated aorta, endothelin-1 induced a slow and sustained contraction in a Ca2+-free medium; after calcium readmission, an additional sustained contraction was elicited. In vascular smooth muscle cells, endothelin-1 provoked a dose-dependent Ca2+ influx that was not inhibited by calcium entry blockers (nifedipine, D 600, or diltiazem). In these cells, [ 125 I]-endothelin-1 bound to a specific, saturable, and high affinity recognition site (Kd about 10(-9) M and Bmax = 52 +/- 2 fmol/10(6) cells). The binding was not reversible and not affected by calcium antagonists. These data do not support the hypothesis that endothelin-1 acts as an endogenous agonist of the voltage-dependent Ca2+ channels. The action of endothelin-1 can be separated into two components: one dependent on Ca2+ influx but insensitive to calcium antagonists and another independent of extracellular Ca2+. The irreversible binding of endothelin-1 may reflect an internalization of the ligand inside the cell membrane, leading to multiple contractile events

  4. Steroid-induced polycystic ovaries in rats: effect of electro-acupuncture on concentrations of endothelin-1 and nerve growth factor (NGF, and expression of NGF mRNA in the ovaries, the adrenal glands, and the central nervous system

    Directory of Open Access Journals (Sweden)

    Aloe Luigi

    2003-04-01

    Full Text Available Abstract Previous studies on the effect of repeated electro-acupuncture (EA treatments in rats with steriod-induced polycystic ovaries (PCO, EA has been shown to modulate nerve growth factor (NGF concentration in the ovaries as well as corticotropin releasing factor (CRF in the median eminence (ME. In the present study we tested the hypothesis that repeated EA treatments modulates sympathetic nerve activity in rats with PCO. This was done by analysing endothelin-1 (ET-1, a potent vasoconstrictor involved in ovarian functions, as well as NGF and NGF mRNA expression involved in the pathophysiological process underlying steroid-induced PCO. The main result in the present study was that concentrations of ET-1 in the ovaries were significantly lower in the PCO group receiving EA compared with the healthy control group (p p p p

  5. Andrographolide inhibits hypoxia-induced hypoxia-inducible factor 1α and endothelin 1 expression through the heme oxygenase 1/CO/cGMP/MKP-5 pathways in EA.hy926 cells.

    Science.gov (United States)

    Lin, Hung-Chih; Su, Shih-Li; Lin, Wan-Chun; Lin, Ai-Hsuan; Yang, Ya-Chen; Lii, Chong-Kuei; Chen, Haw-Wen

    2018-03-01

    Andrographolide is a potent anti-inflammatory agent found in Andrographis paniculata. Endothelin 1 (ET-1) is an endothelium-derived vasoconstrictor with pro-inflammatory properties secreted in response to hypoxia. Mitogen-activated protein kinase phosphatase 5 (MKP-5) is a dual-specificity phosphatase that dephosphorylates threonine and tyrosine residues of MAPKs. We showed previously that hypoxia-induced HIF-1α expression and ET-1 secretion are dependent on p38 MAPK in EA.hy926 cells. Here, we investigate what role MKP-5 plays in andrographolide's inhibition of hypoxia-induced expression of HIF-1α and ET-1. Hypoxic conditions were created using the hypoxia-mimetic agent CoCl 2 . Andrographolide enhanced HO-1 and MKP-5 expression and cellular cGMP content in addition to inhibiting hypoxia-induced ROS generation. Concomitantly, the HO-1 byproduct CO and the cGMP analogue 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) increased MKP-5 expression, and pretreatment with CO and 8-Br-cGMP inhibited hypoxia-induced HIF-1α and ET-1 expression. Transfection of HO-1 siRNA or pretreatment with the HO-1 inhibitor ZnPP-9 or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a specific inhibitor of soluble guanylate cyclase, reduced andrographolide-induced MKP-5 expression. Moreover, silencing MKP-5 or treatment with the phosphatase inhibitor vanadate abrogated andrographolide's suppressing hypoxia-induced p38 MAPK activation and HIF-1α expression. The inhibition of hypoxia-induced HIF-1α and ET-1 expression by andrographolide is likely associated with HO-1/CO/cGMP/MKP-5 pathways, which is involved in inhibiting hypoxia-induced p38 MAPK activation. © 2017 Wiley Periodicals, Inc.

  6. Stimulation of Transforming Growth Factor-β1-Induced Endothelial-To-Mesenchymal Transition and Tissue Fibrosis by Endothelin-1 (ET-1): A Novel Profibrotic Effect of ET-1.

    Science.gov (United States)

    Wermuth, Peter J; Li, Zhaodong; Mendoza, Fabian A; Jimenez, Sergio A

    2016-01-01

    TGF-β-induced endothelial-to-mesenchymal transition (EndoMT) is a newly recognized source of profibrotic activated myofibroblasts and has been suggested to play a role in the pathogenesis of various fibrotic processes. Endothelin-1 (ET-1) has been implicated in the development of tissue fibrosis but its participation in TGF-β-induced EndoMT has not been studied. Here we evaluated the role of ET-1 on TGF-β1-induced EndoMT in immunopurified CD31+/CD102+ murine lung microvascular endothelial cells. The expression levels of α-smooth muscle actin (α-SMA), of relevant profibrotic genes, and of various transcription factors involved in the EndoMT process were assessed employing quantitative RT-PCR, immunofluorescence histology and Western blot analysis. TGF-β1 caused potent induction of EndoMT whereas ET-1 alone had a minimal effect. However, ET-1 potentiated TGF-β1-induced EndoMT and TGF-β1-stimulated expression of mesenchymal cell specific and profibrotic genes and proteins. ET-1 also induced expression of the TGF-β receptor 1 and 2 genes, suggesting a plausible autocrine mechanism to potentiate TGF-β-mediated EndoMT and fibrosis. Stimulation of TGF-β1-induced skin and lung fibrosis by ET-1 was confirmed in vivo in an animal model of TGF-β1-induced tissue fibrosis. These results suggest a novel role for ET-1 in the establishment and progression of tissue fibrosis.

  7. [Association between pulmonary vascular remodeling and expression of hypoxia-inducible factor-1α, endothelin-1 and inducible nitric oxide synthase in pulmonary vessels in neonatal rats with hypoxic pulmonary hypertension].

    Science.gov (United States)

    Wang, Jian-Rong; Zhou, Ying; Sang, Kui; Li, Ming-Xia

    2013-02-01

    To investigate the association between pulmonary vascular remodeling and expression of hypoxia-inducible factor-1α (HIF-1α), endothelin-1 (ET-1) and inducible nitric oxide synthase (iNOS) in pulmonary vessels in neonatal rats with hypoxic pulmonary hypertension (HPH). A neonatal rat model of HPH was established as an HPH group, and normal neonatal rats were enrolled as a control group. The mean pulmonary arterial pressure (mPAP) was measured. The percentage of medial thickness to outer diameter of the small pulmonary arteries (MT%) and the percentage of medial cross-section area to total cross-section area of the pulmonary small arteries (MA%) were measured as the indicators for pulmonary vascular remodeling. The immunohistochemical reaction intensities for HIF-1α, ET-1 and iNOS and their mRNA expression in lung tissues of neonatal rats were measured. Correlation analysis was performed to determine the relationship between pulmonary vascular remodeling and mRNA expression of HIF-1α, ET-1 and iNOS. The mPAP of the HPH group kept increasing on days 3, 5, 7, 10, 14, and 21 of hypoxia, with a significant difference compared with the control group (P<0.05). The HPH group had significantly higher MT% and MA% than the control group from day 7 of hypoxia (P<0.05). HIF-1α protein expression increased significantly on days 3, 5, 7 and 10 days of hypoxia, and HIF-1α mRNA expression increased significantly on days 3, 5 and 7 days of hypoxia in the HPH group compared with the control group (P<0.05). ET-1 protein expression increased significantly on days 3, 5 and 7 days of hypoxia and ET-1 mRNA expression increased significantly on day 3 of hypoxia in the HPH group compared with the control group (P<0.05). Both iNOS protein and mRNA expression were significantly higher on days 3, 5 and 7 days of hypoxia than the control group (P<0.05). Both MT% and MA% were positively correlated with HIF-1α mRNA expression (r=0.835 and 0.850 respectively; P<0.05). Pulmonary vascular

  8. The heart as an extravascular target of endothelin-1 in ...

    Science.gov (United States)

    Exposure to particulate matter air pollution has been causally linked to cardiovascular disease in humans. Several broad and overlapping hypotheses describing the biological mechanisms by which particulate matter exposure leads to cardiovascular disease and cardiac dysfunction have been explored, though linkage with specific factors or genes remains limited. Given evidence pointing to autocrine/paracrine signaling systems as modulators of cardiac dysfunction, the present review highlights the emerging role of endothelins as mediators of cardiac dysfunction following particulate matter exposure. Endothelin-1 is a small multifunctional protein expressed in the pulmonary and cardiovascular system, known for its ability to constrict blood vessels. Although endothelin-1 can also directly and indirectly (via secondary signaling events) modulate cardiac contractility, heart rate, and rhythm, research on the role of endothelins in the context of air pollution has tended to focus on the vascular effects. The plausibility of endothelin as a mechanism underlying particulate matter-induced cardiac dysfunction is further supported by the therapeutic utility of certain endothelin receptor antagonists. Extravascular effects of endothelin on the heart could better explain one mechanism by which particulate matter exposure may lead to cardiac dysfunction. We propose and support the novel hypothesis that autocrine/paracrine signaling systems, such as endothelins, mediate cardiac

  9. Endothelin-1 shifts the mediator of bradykinin-induced relaxation from NO to H2 O2 in resistance arteries from patients with cardiovascular disease

    DEFF Research Database (Denmark)

    Leurgans, Thomas M; Bloksgaard, Maria; Brewer, Jonathan R

    2016-01-01

    -activated K(+) -channels, but markedly blunted by catalase during ET-1-induced contraction. This catalase-sensitive relaxation was not modified by inhibitors of NADPH oxidases or allopurinol. Exogenous H2 O2 caused significantly larger relaxation of ET-1- than K(+) - or U46619-induced contraction...... in the presence of inhibitors of other endothelium-derived relaxing factors. Catalase-sensitive staining of cellular reactive oxygen species with CellROX Deep Red was significantly increased in presence of both 1 μM BK and 2 nM ET-1 but not either peptide alone. CONCLUSIONS AND IMPLICATIONS: In patient resistance...

  10. Interferon Induced Focal Segmental Glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Yusuf Kayar

    2016-01-01

    Full Text Available Behçet’s disease is an inflammatory disease of unknown etiology which involves recurring oral and genital aphthous ulcers and ocular lesions as well as articular, vascular, and nervous system involvement. Focal segmental glomerulosclerosis (FSGS is usually seen in viral infections, immune deficiency syndrome, sickle cell anemia, and hyperfiltration and secondary to interferon therapy. Here, we present a case of FSGS identified with kidney biopsy in a patient who had been diagnosed with Behçet’s disease and received interferon-alpha treatment for uveitis and presented with acute renal failure and nephrotic syndrome associated with interferon.

  11. Nuclear factor κB inhibitor BAY 11-7082 suppresses oxidative stress induced by endothelin-1 (ET-1) in rat kidney.

    Science.gov (United States)

    Kowalczyk, Agata; Kołodziejczyk, Michał; Gorąca, Anna

    2015-12-31

    The aim of the study was to evaluate the effect of BAY 11-7082, an NF-κB inhibitor, on basal and ET-1-induced production of reactive oxygen species (ROS), TNF-α and p65 protein in rat kidney. The experimental animals were divided into five groups (n=7) receiving: 1) saline (control); 2 and 3) ET-1 in a dose of 3 μg/kg body weight (b.w.) or 12.5 μg/kg b.w.; 4) BAY 11-7082 (10 mg/kg b.w.); 5) BAY 11-7082 (10 mg/kg b.w.) and ET-1 (12.5 μg/kg b.w.), respectively. In kidney homogenates the concentration of thiobarbituric acid reactive substances (TBARS), H2O2, TNF-α, p65 protein and GSH/GSSG ratio were determined. ET-1 resulted in a dose-dependent increase in TBARS and hydrogen peroxide (H2O2) levels, and a decrease in GSH/GSSG ratio when compared to the controls. BAY 11-7082 administered 1 h before ET-1 administration at a dose of 12.5 μg/kg resulted in a decrease (PET-1 groups. The level of TNF-α was increased (PET-1, while BAY 11-7082 reduced the TNF-α level (PET-1 induced oxidative stress in kidney tissue. These actions of BAY 11-7082 may result from reduced activity of NF-κB signaling pathways. Inhibition of the NF-κB pathway may be a promising strategy for preventing the progression of kidney damage.

  12. 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

    + exchanger (NCX blockade or by ROS scavenging. Ang II 100 nM increases SS by 70.5±7.6% (p<0.05. This PIE was completely abolished by AT1 receptors blockade and were partially bocked by ET-1 receptors blockade, by NHE inhibition, by reverse mode NCX blockade or by ROS scavenging. Ang II increased preproET-1 mRNA, effect that was blunted by AT1 receptors blockade. We conclude that Ang II induces (through its AT1 receptor release/formation of ET-1, which acting in autocrine fashion on ET receptors of the isolated myocytes increases inotropism through NHE stimulation and NCX reverse mode activation. The participation of ROS is involved is this chain of events.

  13. Andrographolide inhibits hypoxia-induced HIF-1α-driven endothelin 1 secretion by activating Nrf2/HO-1 and promoting the expression of prolyl hydroxylases 2/3 in human endothelial cells.

    Science.gov (United States)

    Lin, Hung-Chih; Su, Shih-Li; Lu, Chia-Yang; Lin, Ai-Hsuan; Lin, Wan-Chun; Liu, Chin-San; Yang, Ya-Chen; Wang, Hsiu-Miao; Lii, Chong-Kuei; Chen, Haw-Wen

    2017-03-01

    Andrographolide, the main bioactive component of the medicinal plant Andrographis paniculata, has been shown to possess potent anti-inflammatory activity. Endothelin 1 (ET-1), a potent vasoconstrictor peptide produced by vascular endothelial cells, displays proinflammatory property. Hypoxia-inducible factor 1α (HIF-1α), the regulatory member of the transcription factor heterodimer HIF-1α/β, is one of the most important molecules that responds to hypoxia. Changes in cellular HIF-1α protein level are the result of altered gene transcription and protein stability, with the latter being dependent on prolyl hydroxylases (PHDs). In this study, inhibition of pro-inflammatory ET-1 expression and changes of HIF-1α gene transcription and protein stability under hypoxia by andrographolide in EA.hy926 endothelial-like cells were investigated. Hypoxic conditions were created using the hypoxia-mimetic agent CoCl 2. We found that hypoxia stimulated the production of reactive oxygen species (ROS), the expression of HIF-1α mRNA and protein, and the expression and secretion of ET-1. These effects, however, were attenuated by co-exposure to andrographolide, bilirubin, and RuCO. Silencing Nrf2 and heme oxygenase 1 (HO-1) reversed the inhibitory effects of andrographolide on hypxoia-induced HIF-1α mRNA and protein expression. Moreover, andrographolide increased the expression of prolyl hydroxylases (PHD) 2/3, which hydroxylate HIF-1α and promotes HIF-1α proteasome degradation, with an increase in HIF-1α hydroxylation was noted under hypoxia. Inhibition of p38 MAPK abrogated the hypoxia-induced increases in HIF-1α mRNA and protein expression as well as ET-1 mRNA expression and secretion. Taken together, these results suggest that andrographolide suppresses hypoxia-induced pro-inflammatory ET-1 expression by activating Nrf2/HO-1, inhibiting p38 MAPK signaling, and promoting PHD2/3 expression. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 918-930, 2017. © 2016 Wiley

  14. Murine study of portal hypertension associated endothelin-1 hypo-response.

    Science.gov (United States)

    Theodorakis, Nicholas; Maluccio, Mary; Skill, Nicholas

    2015-04-28

    To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes. Wild type, eNOS(-/-) and iNOS(-/-) mice received partial portal vein ligation surgery to induce portal hypertension or sham surgery. Development of portal hypertension was determined by measuring the splenic pulp pressure, abdominal aortic flow and portal systemic shunting. To measure splenic pulp pressure, a microtip pressure transducer was inserted into the spleen pulp. Abdominal aortic flow was measured by placing an ultrasonic Doppler flow probe around the abdominal aorta between the diaphragm and celiac artery. Portal systemic shunting was calculated by injection of fluorescent microspheres in to the splenic vein and determining the percentage accumulation of spheres in liver and pulmonary beds. Endothelin-1 hypo-response was evaluated by measuring the change in abdominal aortic flow in response to endothelin-1 intravenous administration. In addition, thoracic aorta endothelin-1 contraction was measured in 5 mm isolated thoracic aorta rings ex-vivo using an ADI small vessel myograph. In wild type and iNOS(-/-) mice splenic pulp pressure increased from 7.5 ± 1.1 mmHg and 7.2 ± 1 mmHg to 25.4 ± 3.1 mmHg and 22 ± 4 mmHg respectively. In eNOS(-/-) mice splenic pulp pressure was increased after 1 d (P = NS), after which it decreased and by 7 d was not significantly elevated when compared to 7 d sham operated controls (6.9 ± 0.6 mmHg and 7.3 ± 0.8 mmHg respectively, P = 0.3). Abdominal aortic flow was increased by 80% and 73% in 7 d portal vein ligated wild type and iNOS when compared to shams, whereas there was no significant difference in 7 d portal vein ligated eNOS(-/-) mice when compared to shams. Endothelin-1 induced a rapid reduction in abdominal aortic blood flow in wild type, eNOS(-/-) and iNOS(-/-) sham mice (50% ± 8%, 73% ± 9% and 47% ± 9% respectively). Following portal vein ligation endothelin-1 reduction in blood flow

  15. Endothelin-1 is a Risk Factor for Pathogenesis of Hypertension

    International Nuclear Information System (INIS)

    Abdelhalim, Mohamed Anwar K.

    2007-01-01

    The purpose of this present study was to investigate the effects of endothelin-1 (ET-1) on the systemic blood pressure, microvascular blood flow velocity and diameter of arterioles and venules of the rat mesentery in vivo. For this purpose, the mesentery was arranged for in situ intravital microscopic observation under transillumination, and cumulative injections of ET-1(30-2000 p mole/kg) were infused intravenously through a catheter inserted into the right jugular vein. Infusion of low doses of ET-1(30-125 pmole/kg) induced a slight increase in the systemic blood pressure, a dose-dependent increase in blood flow velocity of arterioles (20-30 micron m) and venules (30-50 micron m). Diameters of arterioles and venules exhibited no significant change as compared with the control data. On the contrary, the infusion of high doses of ET-1 (250-2000 pmole/kg) induced a long-lasting pressor effect, a dose-dependent decrease in the blood flow velocity of arterioles and venules. Microvascular diameter exhibited a vasoconstrictive effect more prominent in arterioles than in venules. These findings suggest that vasoconstriction produced by ET-1 in rat mesenteric microcirculation may be the causal factor for its potent pressor effect in rats. Moreover, ET-1 may be involved in the regulation of the blood flow velocity distribution of rat mesenteric microcirculation. Finally, ET-1 may be considered as one of the more important risk factors which contribute to the pathogenesis of hypertension. (author)

  16. Venous plasma levels of endothelin-1 are not altered immediately after nitroglycerin infusion in healthy subjects

    DEFF Research Database (Denmark)

    Thomsen, L L; Iversen, Helle Klingenberg; Emmeluth, C

    1995-01-01

    before and immediately (5-30 s) after 80 min infusion of NTG (glyceryl trinitrate) or saline in 12 healthy subjects. On two different days separated by at least 1 week, NTG in four different doses, 0.015, 0.25, 1.0, and 2.0 micrograms. kg-1. min-1, or placebo (isotonic saline) was infused successively...... for 20 min each dose. During the infusion blood pressure and heart rate were measured. NTG infusion significantly decreased systolic blood pressure from 112.4 to 103.4 mmHg and pulse pressure from 39.3 to 29.5 mmHg. Heart rate increased from 62.7 to 73.1 beats. min-1. No changes in endothelin-1 plasma...... levels were induced by NTG infusion (2.4 pg.ml-1 before NTG vs. 2.7 pg.ml-1 after NTG) and placebo infusion also did not affect plasma endothelin-1. It is concluded that venous plasma levels of endothelin-1 are not altered immediately after NTG infusion....

  17. NITRIC OXIDE AND ENDOTHELIN-1 IN CHILDREN WITH DIGESTIVE DISORDERS

    Directory of Open Access Journals (Sweden)

    I. V. Panova

    2012-01-01

    Full Text Available The important part in the group of biological compounds, participating in the regulation of the functions of the gastro-intestinal tract, is assigned to endothelial factors because of their impact on the majority of physiological and pathophysiological processes of the digestive system. The article provides information about physiological role of nitric oxide and endothelin-1 and presents a review of scientific data on the participation of nitric oxide and endothelin-1 in the pathogenesis of many digestive system diseases, emphasizing chronic inflammatory disorders of the upper gastrointestinal tract. The authors accentuate the importance of endothelium endocrine function research in children with esophagogastroduodenal disorders at the beginning of puberty, which is the critical period of ontogenesis.

  18. Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Mortensen, Stefan Peter; Hellsten, Ylva

    2013-01-01

    performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels. CONCLUSION: Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes......AIMS: Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension...... and age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects. METHODS: In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study...

  19. Relaxing Responses to Hydrogen Peroxide and Nitric Oxide in Human Pericardial Resistance Arteries Stimulated with Endothelin-1

    DEFF Research Database (Denmark)

    Leurgans, Thomas M; Bloksgaard, Maria; Irmukhamedov, Akhmadjon

    2018-01-01

    In human pericardial resistance arteries, effects of the endothelium-dependent vasodilator bradykinin are mediated by NO during contraction induced by K(+) or the TxA2 analogue U46619 and by H2 O2 during contraction by endothelin-1 (ET-1), respectively. We tested the hypotheses that ET-1 reduces...... also acts as an endothelium-dependent vasodilator. This article is protected by copyright. All rights reserved....

  20. Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats

    OpenAIRE

    Glendenning, Michele L.; Lovekamp-Swan, Tara; Schreihofer, Derek A.

    2008-01-01

    Estrogen is a powerful endogenous and exogenous neuroprotective agent in animal models of brain injury, including focal cerebral ischemia. Although this protection has been demonstrated in several different treatment and injury paradigms, it has not been demonstrated in focal cerebral ischemia induced by intraparenchymal endothelin-1 injection, a model with many advantages over other models of experimental focal ischemia. Reproductively mature female Sprague-Dawley rats were ovariectomized an...

  1. Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension.

    Science.gov (United States)

    Nyberg, M; Mortensen, S P; Hellsten, Y

    2013-03-01

    Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension and age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects. In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study 2, young (23 ± 1 years, n = 8), older lifelong sedentary (66 ± 2 years, n = 8) and older lifelong endurance-trained (62 ± 2 years, n = 8) subjects were studied in a cross-sectional design. Skeletal muscle and plasma endothelin-1 levels were increased with age and plasma endothelin-1 levels were higher in hypertensive than normotensive individuals. Eight weeks of exercise training normalized plasma endothelin-1 levels in the hypertensive subjects and increased the protein expression of the ET(A) receptor in skeletal muscle of normotensive subjects. Similarly, individuals that had performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels. Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension. This effect may explain some of the beneficial effects of training on the cardiovascular system in older and hypertensive subjects. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

  2. Activation of either the ETA or the ETB receptors is involved in the development of electrographic seizures following intrahippocampal infusion of the endothelin-1 in immature rats

    Czech Academy of Sciences Publication Activity Database

    Tsenov, Grygoriy; Vondráková, Kateřina; Otáhal, Jakub; Burchfiel, J.; Kubová, Hana

    2015-01-01

    Roč. 265, Mar 2015 (2015), s. 40-47 ISSN 0014-4886 R&D Projects: GA ČR(CZ) GPP304/11/P386; GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GA14-20613S Institutional support: RVO:67985823 Keywords : focal ischemia * endothelin-1 * cerebral blood flow * oxygen saturation * seizures * hippocampus * immature rat * ET receptors Subject RIV: FH - Neurology Impact factor: 4.657, year: 2015

  3. UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling.

    Science.gov (United States)

    Moore, Carlene; Cevikbas, Ferda; Pasolli, H Amalia; Chen, Yong; Kong, Wei; Kempkes, Cordula; Parekh, Puja; Lee, Suk Hee; Kontchou, Nelly-Ange; Yeh, Iwei; Ye, Iwei; Jokerst, Nan Marie; Fuchs, Elaine; Steinhoff, Martin; Liedtke, Wolfgang B

    2013-08-20

    At our body surface, the epidermis absorbs UV radiation. UV overexposure leads to sunburn with tissue injury and pain. To understand how, we focus on TRPV4, a nonselective cation channel highly expressed in epithelial skin cells and known to function in sensory transduction, a property shared with other transient receptor potential channels. We show that following UVB exposure mice with induced Trpv4 deletions, specifically in keratinocytes, are less sensitive to noxious thermal and mechanical stimuli than control animals. Exploring the mechanism, we find that epidermal TRPV4 orchestrates UVB-evoked skin tissue damage and increased expression of the proalgesic/algogenic mediator endothelin-1. In culture, UVB causes a direct, TRPV4-dependent Ca(2+) response in keratinocytes. In mice, topical treatment with a TRPV4-selective inhibitor decreases UVB-evoked pain behavior, epidermal tissue damage, and endothelin-1 expression. In humans, sunburn enhances epidermal expression of TRPV4 and endothelin-1, underscoring the potential of keratinocyte-derived TRPV4 as a therapeutic target for UVB-induced sunburn, in particular pain.

  4. Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral Malaria.

    Directory of Open Access Journals (Sweden)

    Brandi D Freeman

    2016-03-01

    Full Text Available Plasmodium falciparum infection causes a wide spectrum of diseases, including cerebral malaria, a potentially life-threatening encephalopathy. Vasculopathy is thought to contribute to cerebral malaria pathogenesis. The vasoactive compound endothelin-1, a key participant in many inflammatory processes, likely mediates vascular and cognitive dysfunctions in cerebral malaria. We previously demonstrated that C57BL6 mice infected with P. berghei ANKA, our fatal experimental cerebral malaria model, sustained memory loss. Herein, we demonstrate that an endothelin type A receptor (ETA antagonist prevented experimental cerebral malaria-induced neurocognitive impairments and improved survival. ETA antagonism prevented blood-brain barrier disruption and cerebral vasoconstriction during experimental cerebral malaria, and reduced brain endothelial activation, diminishing brain microvascular congestion. Furthermore, exogenous endothelin-1 administration to P. berghei NK65-infected mice, a model generally regarded as a non-cerebral malaria negative control for P. berghei ANKA infection, led to experimental cerebral malaria-like memory deficits. Our data indicate that endothelin-1 is critical in the development of cerebrovascular and cognitive impairments with experimental cerebral malaria. This vasoactive peptide may thus serve as a potential target for adjunctive therapy in the management of cerebral malaria.

  5. The insulinotropic effect of endothelin-1 is mediated by glucagon release from the islet alpha cells

    DEFF Research Database (Denmark)

    Brock, B; Gregersen, S; Kristensen, K

    1999-01-01

    AIMS/HYPOTHESIS: The circulating concentrations of endothelin-1 (ET-1), a peptide derived from endothelium, are increased in hypertension and diabetes. Endothelin-1 has recently been shown to be an insulinotropic agent. The mechanism of action of endothelin-1 on the endocrine pancreas has not yet...... been clarified. METHODS: We investigated the action of endothelin-1 on the insulin secretion, the binding of (125)I-ET-1 to beta cells as well as its effects on purified beta and non-beta cells from normal rats. The expression of endothelin receptors in alpha- and beta-cell lines and in normal rat...... from purified beta cells. Endothelin-1-(100 nmol/l) increased, however, both insulin and glucagon secretion from a mixture of purified beta and non-beta cells indicating that alpha cells seem to have a key role for the action of ET-1 on insulin secretion. CONCLUSION/INTERPRETATION: The insulinotropic...

  6. Endothelin-1 is associated with fibrosis in proliferative diabetic retinopathy membranes.

    Science.gov (United States)

    Chang, William; Lajko, Michelle; Fawzi, Amani A

    2018-01-01

    To characterize the relationship between endothelin-1 and fibrosis in epiretinal membranes in proliferative diabetic retinopathy and explore the role of endothelial-mesenchymal transition in these membranes. Membranes were obtained from eyes undergoing pars plana vitrectomy for complicated proliferative diabetic retinopathy or idiopathic epiretinal membrane. Through standard immunohistochemical techniques, we labeled membranes to explore the distribution of endothelin-1 and endothelin receptor B, comparing proliferative diabetic retinopathy and idiopathic epiretinal membranes. In addition, membranes were also labeled with markers for fibroblasts, endothelial, and glial cells and studied with confocal laser scanning microscopy. The intensity of endothelin-1 labeling was quantified using standard image analysis software. Fourteen membranes were included in the analysis, nine from eyes with proliferative diabetic retinopathy and five idiopathic membranes. Flatmount diabetic membranes showed co-localization of endothelin-1 with S100A4 and CD31. Immunohistochemistry and quantitative analysis of cross-sectional membranes showed significantly higher endothelin-1 labeling in proliferative diabetic retinopathy membranes compared to idiopathic membranes (pmembranes showed more elements staining positive for S100A4 compared to idiopathic membranes. Epiretinal membrane formation in proliferative diabetic retinopathy involves higher tissue levels of endothelin-1 and fibroblastic activity. Furthermore, endothelin-1, endothelial and fibroblastic staining appear to be correlated, suggestive of endothelial-to-mesenchymal transition in proliferative diabetic retinopathy.

  7. Endothelin-1 and Exercise Intensity in Sedentary Adolescents with Obesity

    Directory of Open Access Journals (Sweden)

    Brooke E. Starkoff

    2015-01-01

    Full Text Available Inactivity combined with obesity during adolescence increases the risk of future cardiovascular disease. The study purpose was to compare the influence of differing intensities of exercise on endothelial function in sedentary adolescents with obesity. Participants were randomized to one of two groups in a 6-week exercise intervention: moderate intensity (MOD or high intensity interval exercise (HIIE. Endothelial function was assessed pre- and post-intervention via fasted serum levels of endothelin-1 (ET-1. Pre-measures of ET-1 concentrations were elevated at baseline. No significant differences in ET-1 were found between or within exercise groups. However, in the HIIE group, ET-1 was inversely associated with percentages of age predicted maximal heart rate achieved during the intervention (p=0.035, r=-0.567. The exercise interventions did not positively change ET-1 levels, yet participants who exercised at higher intensities in the HIIE group experienced greater decreases in ET-1. Keywords: childhood obesity, endothelial function, high intensity interval exercise

  8. Facial hyperalgesia due to direct action of endothelin-1 in the trigeminal ganglion of mice.

    Science.gov (United States)

    Gomes, Lenyta Oliveira; Chichorro, Juliana Geremias; Araya, Erika Ivanna; de Oliveira, Jade; Rae, Giles Alexander

    2018-03-23

    This study assessed the ability of endothelin-1 (ET-1) to evoke heat hyperalgesia when injected directly into the trigeminal ganglia (TG) of mice and determined the receptors implicated in this effect. The effects of TG ET A and ET B receptor blockade on alleviation of heat hyperalgesia in a model of trigeminal neuropathic pain induced by infraorbital nerve constriction (CION) were also examined. Naive mice received an intraganglionar (i.g.) injection of ET-1 (0.3-3 pmol) or the selective ET B R agonist sarafotoxin S6c (3-30 pmol), and response latencies to ipsilateral heat stimulation were assessed before the treatment and at 1-h intervals up to 5 h after the treatment. Heat hyperalgesia induced by i.g. ET-1 or CION was assessed after i.g. injections of ET A R and ET B R antagonists (BQ-123 and BQ-788, respectively, each at 0.5 nmol). Intraganglionar ET-1 or sarafotoxin S6c injection induced heat hyperalgesia lasting 4 and 2 h, respectively. Heat hyperalgesia induced by ET-1 was attenuated by i.g. BQ-123 or BQ-788. On day 5 after CION, i.g. BQ-788 injection produced a more robust antihyperalgesic effect compared with BQ-123. ET-1 injection into the TG promotes ET A R/ET B R-mediated facial heat hyperalgesia, and both receptors are clearly implicated in CION-induced hyperalgesia in the murine TG system. © 2018 Royal Pharmaceutical Society.

  9. Cerebrovascular endothelin-1 hyper-reactivity is associated with transient receptor potential canonical channels 1 and 6 activation and delayed cerebral hypoperfusion after forebrain ischaemia in rats

    DEFF Research Database (Denmark)

    Johansson, S E; Andersen, X E D R; Hansen, R H

    2015-01-01

    . METHODS: Experimental forebrain ischaemia was induced in Wistar male rats by a two-vessel occlusion model, and the cerebral blood flow was measured by magnetic resonance imaging two days after reperfusion. In vitro vasoreactivity studies, immunofluorescence and quantitative PCR were performed on cerebral...... in the vascular smooth muscle cells was enhanced and correlated with decreased cerebral blood flow two days after forebrain ischaemia. Furthermore, under conditions when voltage-dependent calcium channels were inhibited, endothelin-1-induced cerebrovascular contraction was enhanced and this enhancement...... was presumably mediated by Ca(2+) influx via upregulated transient receptor potential canonical channels 1 and 6. CONCLUSIONS: Our data demonstrates that endothelin-1-mediated influx of extracellular Ca(2+) activates transient receptor potential canonical channels 1 and 6 in cerebral vascular smooth muscle cells...

  10. Elevated plasma endothelin-1 and pulmonary arterial pressure in children exposed to air pollution.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Vincent, Renaud; Mora-Tiscareño, Antonieta; Franco-Lira, Maricela; Henríquez-Roldán, Carlos; Barragán-Mejía, Gerardo; Garrido-García, Luis; Camacho-Reyes, Laura; Valencia-Salazar, Gildardo; Paredes, Rogelio; Romero, Lina; Osnaya, Hector; Villarreal-Calderón, Rafael; Torres-Jardón, Ricardo; Hazucha, Milan J; Reed, William

    2007-08-01

    Controlled exposures of animals and humans to particulate matter (PM) or ozone air pollution cause an increase in plasma levels of endothelin-1, a potent vasoconstrictor that regulates pulmonary arterial pressure. The primary objective of this field study was to determine whether Mexico City children, who are chronically exposed to levels of PM and O(3) that exceed the United States air quality standards, have elevated plasma endothelin-1 levels and pulmonary arterial pressures. We conducted a study of 81 children, 7.9 +/- 1.3 years of age, lifelong residents of either northeast (n = 19) or southwest (n = 40) Mexico City or Polotitlán (n = 22), a control city with PM and O(3) levels below the U.S. air quality standards. Clinical histories, physical examinations, and complete blood counts were done. Plasma endothelin-1 concentrations were determined by immunoassay, and pulmonary arterial pressures were measured by Doppler echocardiography. Mexico City children had higher plasma endothelin-1 concentrations compared with controls (p < 0.001). Mean pulmonary arterial pressure was elevated in children from both northeast (p < 0.001) and southwest (p < 0.05) Mexico City compared with controls. Endothelin-1 levels in Mexico City children were positively correlated with daily outdoor hours (p = 0.012), and 7-day cumulative levels of PM air pollution < 2.5 mum in aerodynamic diameter (PM(2.5)) before endothelin-1 measurement (p = 0.03). Chronic exposure of children to PM(2.5) is associated with increased levels of circulating endothelin-1 and elevated mean pulmonary arterial pressure.

  11. Elevated Plasma Endothelin-1 and Pulmonary Arterial Pressure in Children Exposed to Air Pollution

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Vincent, Renaud; Mora-Tiscareño, Antonieta; Franco-Lira, Maricela; Henríquez-Roldán, Carlos; Barragán-Mejía, Gerardo; Garrido-García, Luis; Camacho-Reyes, Laura; Valencia-Salazar, Gildardo; Paredes, Rogelio; Romero, Lina; Osnaya, Hector; Villarreal-Calderón, Rafael; Torres-Jardón, Ricardo; Hazucha, Milan J.; Reed, William

    2007-01-01

    Background Controlled exposures of animals and humans to particulate matter (PM) or ozone air pollution cause an increase in plasma levels of endothelin-1, a potent vasoconstrictor that regulates pulmonary arterial pressure. Objectives The primary objective of this field study was to determine whether Mexico City children, who are chronically exposed to levels of PM and O3 that exceed the United States air quality standards, have elevated plasma endothelin-1 levels and pulmonary arterial pressures. Methods We conducted a study of 81 children, 7.9 ± 1.3 years of age, lifelong residents of either northeast (n = 19) or southwest (n = 40) Mexico City or Polotitlán (n = 22), a control city with PM and O3 levels below the U.S. air quality standards. Clinical histories, physical examinations, and complete blood counts were done. Plasma endothelin-1 concentrations were determined by immunoassay, and pulmonary arterial pressures were measured by Doppler echocardiography. Results Mexico City children had higher plasma endothelin-1 concentrations compared with controls (p < 0.001). Mean pulmonary arterial pressure was elevated in children from both northeast (p < 0.001) and southwest (p < 0.05) Mexico City compared with controls. Endothelin-1 levels in Mexico City children were positively correlated with daily outdoor hours (p = 0.012), and 7-day cumulative levels of PM air pollution < 2.5 μm in aerodynamic diameter (PM2.5) before endothelin-1 measurement (p = 0.03). Conclusions Chronic exposure of children to PM2.5 is associated with increased levels of circulating endothelin-1 and elevated mean pulmonary arterial pressure. PMID:17687455

  12. Different pressor and bronchoconstrictor properties of human big-endothelin-1, 2 (1-38) and 3 in ketamine/xylazine-anaesthetized guinea-pigs.

    OpenAIRE

    Gratton, J P; Rae, G A; Claing, A; Télémaque, S; D'Orléans-Juste, P

    1995-01-01

    1. In the present study, the precursors of endothelin-1, endothelin-2 and endothelin-3 were tested for their pressor and bronchoconstrictor properties in the anaesthetized guinea-pig. In addition, the effects of big-endothelin-1 and endothelin-1 were assessed under urethane or ketamine/xylazine anaesthesia. 2. When compared to ketamine/xylazine, urethane markedly depressed the pressor and bronchoconstrictor properties of endothelin-1 and big-endothelin-1. 3. Under ketamine/xylazine anaesthesi...

  13. Endothelin-1 and endothelin-3 in cirrhosis: relations to systemic and splanchnic haemodynamics

    DEFF Research Database (Denmark)

    Møller, S; Gülberg, V; Gerbes, A L

    1995-01-01

    correlated with the hepatic venous pressure gradient (r = 0.61, p blood pressure (r = -0.31, p blood volume (-0.36, p ... haemodynamics. METHODS: Endothelin-1 and endothelin-3 were measured in samples from a hepatic vein and the femoral artery in 42 patients with cirrhosis, eight hypertensive controls and 10 normotensive controls. RESULTS: Hepatic venous endothelin-1 was significantly higher in the patients with cirrhosis, mean 21.......002). The same pattern was found in arterial endothelin-3. Hepatic venous endothelin-3 correlated significantly with central and arterial blood volume (r = 0.56, p

  14. Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

    International Nuclear Information System (INIS)

    Lin, Yan-Jie; Juan, Chi-Chang; Kwok, Ching-Fai; Hsu, Yung-Pei; Shih, Kuang-Chung; Chen, Chin-Chang; Ho, Low-Tone

    2015-01-01

    Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ET A R during insulin resistance, ET A R expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ET A R expression, but not ET B R, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ET A R pathway suppressed insulin-induced

  15. Regular aerobic exercise reduces endothelin-1-mediated vasoconstrictor tone in overweight and obese adults.

    Science.gov (United States)

    Dow, Caitlin A; Stauffer, Brian L; Brunjes, Danielle L; Greiner, Jared J; DeSouza, Christopher A

    2017-09-01

    What is the central question of this study? Does aerobic exercise training reduce endothelin-1 (ET-1)-mediated vasoconstrictor tone in overweight/obese adults? And, if so, does lower ET-1 vasoconstriction underlie the exercise-related enhancement in endothelium-dependent vasodilatation in overweight/obese adults? What is the main finding and its importance? Regular aerobic exercise reduces ET-1-mediated vasoconstrictor tone in previously sedentary overweight/obese adults, independent of weight loss. Decreased ET-1 vasoconstriction is an important mechanism underlying the aerobic exercise-induced improvement in endothelium-dependent vasodilator function in overweight/obese adults. Endothelin-1 (ET-1)-mediated vasoconstrictor tone is elevated in overweight and obese adults, contributing to vasomotor dysfunction and increased cardiovascular disease risk. Although the effects of habitual aerobic exercise on endothelium-dependent vasodilatation in overweight/obese adults have been studied, little is known regarding ET-1-mediated vasoconstriction. Accordingly, the aims of the present study were to determine the following: (i) whether regular aerobic exercise training reduces ET-1-mediated vasoconstrictor tone in overweight and obese adults; and, if so, (ii) whether the reduction in ET-1-mediated vasoconstriction contributes to exercise-induced improvement in endothelium-dependent vasodilatation in this population. Forearm blood flow (FBF) in response to intra-arterial infusion of selective ET A receptor blockade (BQ-123, 100 nmol min -1 for 60 min), acetylcholine [4.0, 8.0 and 16.0 μg (100 ml tissue) -1  min -1 ] in the absence and presence of ET A receptor blockade and sodium nitroprusside [1.0, 2.0 and 4.0 μg (100 ml tissue) -1  min -1 ] were determined before and after a 3 month aerobic exercise training intervention in 25 (16 men and nine women) overweight/obese (body mass index 30.1 ± 0.5 kg m -2 ) adults. The vasodilator response to BQ-123 was

  16. Study of Endothelin-1 and Vascular Endothelial Growth Factor in Patients with Cancer Colon

    International Nuclear Information System (INIS)

    ABDEL-GAWAD, I.A.; HASSANEIN, H.M.R.; BAHGAT, N.A.; ABDEL SATTAR, M.A.; EL-SISSY, A.H.; ALTAWEEL, M.A.; HELAL, A.M.

    2008-01-01

    Purpose: The levels of endothelin-1 and VEGF were evaluated in the sera of newly diagnosed patients with cancer colon and were compared with the routinely used tumor markers; CEA and CA19.9. Their relations with some prognostic factors of cancer colon were also investigated. Subjects and Methods: The study included 48 patients with cancer colon and 20 apparently healthy volunteers as a control group. Patients were 23 males and 25 females with age range from 18 to 71 years (mean = 47±1.8). Both serum and plasma samples were obtained from patients and controls. Results: Six percent of patients had grade 1 tumors, 77% had grade 2 and 17% had grade 3 disease. As regard to the stage, 52% of patients were stage II, 35.5% were stage III, while 12.5% were stage IV. Liver metastasis was present in 12.5%, while 35% showed lymph node metastasis. The VEGF, endothelin-1, CA 19.9 and CEA were significantly higher in the cancer colon patients than in control groups (p-value <0.001, 0.006, <0.001 and <0.001; respectively). Plasma level of endothelin-1 and serum level of VEGF showed significantly higher levels in advanced stages of the disease (p value <0 .001) and in presence of liver metastasis (p value <0.001 and 0.002 respectively), while VEGF showed significant result when compared with the grade (p value=0.032). In this study, when comparing the levels of plasma endothelin-1 and serum VEGF between the metastatic, non-metastatic liver patients of the cancer colon group and the control group, the comparison was statistically significant for both markers (p<0.001). Endothelin-1 and VEGF showed significant positive correlation (r=0.77 and p-value <0.0001). Serum VEGF and CA 19.9 showed good sensitivities which were not different (97.9% and 87.5%; respectively), while there was no significant difference between VEGF, CA 19.9 and CEA with respect to specificities (100%, 90% and 100% respectively). Conclusion: Both endothelin-1 and VEGF may be used for early detection of liver

  17. Association of endothelin-1 expression and cartilaginous endplate degeneration in humans.

    Directory of Open Access Journals (Sweden)

    Wei Yuan

    Full Text Available BACKGROUND: Inflammatory cytokines are involved in intervertebral disc (IVD degeneration. Endothelin-1 (ET-1, a 21-amino-acid cytokine implicated with cartilage degradation, is secreted by vascular endothelial cells and also by many other cell types. The expression of ET-1 in human IVD cartilage endplate (CEP and its role in disc degeneration have not been explored. METHODS AND FINDINGS: The expression of ET-1 in degenerated CEP was analyzed by immunohistochemical staining and Western blotting; ET-1 was demonstrated in cartilaginous endplate cells (CECs by immunofluorescent staining. The ET-1 mRNA expression and protein production by CECs stimulated by tumor necrosis factor alpha (TNF-α, a pro-inflammatory cytokine, were determined by real-time PCR analysis and Western blotting, respectively. The matrix metalloprotease-1 (MMP-1, MMP-13 and tissue inhibitor of metalloproteases-1 (TIMP-1 levels in the supernatant of cultured CECs treated with ET-1 were determined using enzyme-linked immunosorbent assays. Nitric oxide (NO release and nitric oxide synthase (NOS activity were measured using a spectrophotometric assay. The apoptosis of CECs by ET-1 was measured by an Annexin V-FITC detection assay. The production of ET-1 in degenerated cartilage endplate was significantly higher than normal CEP. The results showed that ET-1 was expressed by CECs and modulated by TNF-α in a dose-dependent manner. ET-1 increased production of MMP-1 and MMP-13, decreased TIMP-1 production, and induced NO and NOS release by cultured CECs. The direct stimulation of CECs by ET-1 did not promote cell apoptosis. CONCLUSION: The study results suggest that ET-1 played a pivotal role in human CEP degeneration, and may be a new target for development of therapies for this condition.

  18. Lactoferrin- Endothelin-1 Axis Contributes to the Development and Invasiveness of Triple Negative Breast Cancer Phenotypes

    Science.gov (United States)

    Ha, Ngoc-Han; Nair, Vasudha; Reddy, Divijendra Natha Sirigiri; Mudvari, Prakriti; Ohshiro, Kazufumi; Ghanta, Krishna Sumanth; Pakala, Suresh B.; Li, Da-Qiang; Costa, Luis; Lipton, Allan; Badwe, Rajendra A.; Fuqua, Suzanne; Wallon, Margaretha; Prendergast, George C.; Kumar, Rakesh

    2013-01-01

    Triple-negative breast cancer (TNBC) is characterized by the lack of expression of ERα, PR and HER-2 receptors and the pathway(s) responsible for this downregulation and thus aggressiveness, remains unknown. Here we discovered that lactoferrin (Lf) efficiently downregulates the levels of ERα, PR and HER-2 receptors in a proteasome-dependent manner in breast cancer cells, and accounts for the loss of responsiveness to ER- or HER-2- targeted therapies. Further we found that Lf increases migration and invasiveness of both non-TNBC and TNBC cell lines. We discovered that Lf directly stimulates the transcription of endothelin-1 (ET-1), a secreted pro-invasive polypeptide that acts through a specific receptor ET(A)R, leading to secretion of bioactive ET-1 peptide. Interestingly, a therapeutic ET-1 receptor antagonist drug completely blocked Lf-dependent motility and invasiveness of breast cancer cells. Physiologic significance of this newly discovered Lf-ET-1 axis in the manifestation of TNBC phenotypes is revealed by elevated plasma and tissue Lf and ET-1 levels in TNBC patients as compared to those in ER+ cases. These findings describe the first physiologically relevant polypeptide as a functional determinant of downregulating all three therapeutic receptors in breast cancer which utilizes another secreted ET-1 system to confer invasiveness. Results presented here provide proof-of-principle evidence in support of therapeutic effectiveness of ET-1 receptor antagonist to completely block the Lf-induced motility and invasiveness of the TNBC as well as non-TBNC cells, and thus, opening a remarkable opportunity to treat TNBC by targeting the Lf-ET-1 axis using an approved developmental drug. PMID:22006997

  19. The mechanism of action of endothelin-1 as compared with other agonists in vascular smooth muscle

    International Nuclear Information System (INIS)

    Wallnoefer, A.W.; Weir, S.; Rueegg, U.C.; Cauvin, C.

    1989-01-01

    The effects of endothelin-1 (ET-1) on tension and membrane potential in rat isolated mesenteric resistance vessels (MRVs) and on 45Ca influx, 45Ca efflux, inositol-1,4,5-triphosphate (IP3) production, and cytoplasmic Ca2+ concentration ([Ca2+]1) in cultured aortic smooth muscle cells were compared with those of other agonists. ET-1 induced contractions of the MRVs, which were slow in onset, but reached a similar maximum amplitude (at 10 nM ET-1) as that seen with norepinephrine (NE, 10 microM) or [arg8]vasopressin (AVP, 0.1 microM). The EC50 for ET-1 was 1.3 +/- 0.1 nM. Removal of extracellular Ca2+ reduced ET-1-induced contractions to 11 +/- 3% of those in Ca2+-containing medium. With NE, the same procedure reduced contractions to 47 +/- 7% of those in Ca2+-containing medium, while with AVP, the reduction was similar in magnitude to that induced by ET-1 (11 +/- 5% of those in Ca2+-containing medium). Relaxation of ET-1-induced and NE-induced contractions by diltiazem was not complete (maximal at 58 +/- 6% with 10 microM diltiazem after 6 nM ET-1, and at 70 +/- 3% after 0.1 microM NE), in contrast to that of 80 mM K+-induced contractions, which were potently (IC50 = 0.2 microM) and completely reversed (100% relaxation at 10 microM diltiazem). ET-1 (6 nM) caused a small but significant depolarization of the MRVs (approximately 7 mV), the magnitude of which was only about one-third of that induced by equieffective contractile concentrations of NE and AVP. The voltage-sensitive Ca2+ channel agonist Bay K 8644 (1 microM), in contrast to ET-1, NE, and AVP, produced a small contraction (30 +/- 2% of the maximum response to NE), but no further depolarization when added in the presence of 15 mM K+ (which elicited approximately 12 mV depolarization but no contraction)

  20. Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yan-Jie [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China); Juan, Chi-Chang [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Kwok, Ching-Fai [Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Hsu, Yung-Pei [Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China); Shih, Kuang-Chung [Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Chen, Chin-Chang [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Ho, Low-Tone, E-mail: ltho@vghtpe.gov.tw [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China)

    2015-05-08

    Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ET{sub A}R during insulin resistance, ET{sub A}R expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ET{sub A}R expression, but not ET{sub B}R, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ET{sub A}R pathway

  1. Effect of endothelin-1 on the excitability of rat cortical and hippocampal slices in vitro

    Czech Academy of Sciences Publication Activity Database

    Konopková, Renata; Világi, I.; Borbély, S.; Kubová, Hana; Otáhal, Jakub

    2012-01-01

    Roč. 61, č. 2 (2012), s. 215-219 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LC554; GA AV ČR(CZ) 1QS501210509; GA ČR(CZ) GD305/08/H037 Institutional research plan: CEZ:AV0Z50110509 Keywords : Endothelin-1 * excitability * hippocampus * somatosensory cortex * rat * epileptogenesis Subject RIV: FH - Neurology Impact factor: 1.531, year: 2012

  2. Binding sites for endothelin-1 in rat tissues: An autoradiographic study

    International Nuclear Information System (INIS)

    Koseki, C.; Imai, M.; Hirata, Y.; Yanagisawa, M.; Masaki, T.

    1989-01-01

    By tissue autoradiography in the rat, we demonstrated that receptors for endothelin-1 (ET-1) were distributed not only in the cardiovascular system but also in the noncardiovascular organs including the brain, lung, intestine, etc. In the brain, the receptors were mainly found in the basal ganglia and brainstem, in which nuclei are known to be cardiovascular regulatory sites. In addition to its direct vasoconstricting action, ET-1 may exert neural cardiovascular control as a neuropeptide

  3. Endothelin-1 stimulates the release of preloaded [3H]D-aspartate from cultured cerebellar granule cells

    International Nuclear Information System (INIS)

    Lin, W.W.; Lee, C.Y.; Chuang, D.M.

    1990-01-01

    We have recently reported that endothelin-1 (ET) induces phosphoinositide hydrolysis in primary cultures of rat cerebellar granule cells. Here we found that ET in a dose-dependent manner (1-30 nM) stimulated the release of preloaded [ 3 H]D-aspartate from granule cells. The ET-induced aspartate release was completely blocked in the absence of extracellular Ca 2+ , but was unaffected by 1 mM Co 2+ or 1 microM dihydropyridine derivatives (nisoldipine and nimodipine). At higher concentration (10 microM) of nisoldipine and nimodipine, the release was partially inhibited. Short-term pretreatment of cells with phorbol 12,13-dibutyrate (PDBu) potentiated the ET-induced aspartate release, while long-term pretreatment with PDBu attenuated the release. Long-term exposure of cells to pertussis toxin (PTX), on the other hand, potentiated the ET-induced effects. Our results suggest that ET has a neuromodulatory function in the central nervous system

  4. Endothelin-1 stimulates the release of preloaded ( sup 3 H)D-aspartate from cultured cerebellar granule cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, W.W.; Lee, C.Y.; Chuang, D.M. (NIMH Neuroscience Center, Washington, DC (USA))

    1990-03-16

    We have recently reported that endothelin-1 (ET) induces phosphoinositide hydrolysis in primary cultures of rat cerebellar granule cells. Here we found that ET in a dose-dependent manner (1-30 nM) stimulated the release of preloaded ({sup 3}H)D-aspartate from granule cells. The ET-induced aspartate release was completely blocked in the absence of extracellular Ca{sup 2+}, but was unaffected by 1 mM Co{sup 2+} or 1 microM dihydropyridine derivatives (nisoldipine and nimodipine). At higher concentration (10 microM) of nisoldipine and nimodipine, the release was partially inhibited. Short-term pretreatment of cells with phorbol 12,13-dibutyrate (PDBu) potentiated the ET-induced aspartate release, while long-term pretreatment with PDBu attenuated the release. Long-term exposure of cells to pertussis toxin (PTX), on the other hand, potentiated the ET-induced effects. Our results suggest that ET has a neuromodulatory function in the central nervous system.

  5. Elevated levels of plasma Big endothelin-1 and its relation to hypertension and skin lesions in individuals exposed to arsenic

    International Nuclear Information System (INIS)

    Hossain, Ekhtear; Islam, Khairul; Yeasmin, Fouzia; Karim, Md. Rezaul; Rahman, Mashiur; Agarwal, Smita; Hossain, Shakhawoat; Aziz, Abdul; Al Mamun, Abdullah; Sheikh, Afzal; Haque, Abedul; Hossain, M. Tofazzal; Hossain, Mostaque; Haris, Parvez I.; Ikemura, Noriaki; Inoue, Kiyoshi; Miyataka, Hideki; Himeno, Seiichiro; Hossain, Khaled

    2012-01-01

    Chronic arsenic (As) exposure affects the endothelial system causing several diseases. Big endothelin-1 (Big ET-1), the biological precursor of endothelin-1 (ET-1) is a more accurate indicator of the degree of activation of the endothelial system. Effect of As exposure on the plasma Big ET-1 levels and its physiological implications have not yet been documented. We evaluated plasma Big ET-1 levels and their relation to hypertension and skin lesions in As exposed individuals in Bangladesh. A total of 304 study subjects from the As-endemic and non-endemic areas in Bangladesh were recruited for this study. As concentrations in water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The plasma Big ET-1 levels were measured using a one-step sandwich enzyme immunoassay kit. Significant increase in Big ET-1 levels were observed with the increasing concentrations of As in drinking water, hair and nails. Further, before and after adjusting with different covariates, plasma Big ET-1 levels were found to be significantly associated with the water, hair and nail As concentrations of the study subjects. Big ET-1 levels were also higher in the higher exposure groups compared to the lowest (reference) group. Interestingly, we observed that Big ET-1 levels were significantly higher in the hypertensive and skin lesion groups compared to the normotensive and without skin lesion counterpart, respectively of the study subjects in As-endemic areas. Thus, this study demonstrated a novel dose–response relationship between As exposure and plasma Big ET-1 levels indicating the possible involvement of plasma Big ET-1 levels in As-induced hypertension and skin lesions. -- Highlights: ► Plasma Big ET-1 is an indicator of endothelial damage. ► Plasma Big ET-1 level increases dose-dependently in arsenic exposed individuals. ► Study subjects in arsenic-endemic areas with hypertension have elevated Big ET-1 levels. ► Study subjects with arsenic-induced

  6. Elevated levels of plasma Big endothelin-1 and its relation to hypertension and skin lesions in individuals exposed to arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Hossain, Ekhtear; Islam, Khairul; Yeasmin, Fouzia [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi-6205 (Bangladesh); Karim, Md. Rezaul [Department of Applied Nutrition and Food Technology, Islamic University, Kushtia-7003 (Bangladesh); Rahman, Mashiur; Agarwal, Smita; Hossain, Shakhawoat; Aziz, Abdul; Al Mamun, Abdullah; Sheikh, Afzal; Haque, Abedul; Hossain, M. Tofazzal [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi-6205 (Bangladesh); Hossain, Mostaque [Department of Medicine, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), Dhaka (Bangladesh); Haris, Parvez I. [Faculty of Health and Life Sciences, De Montfort University, Leicester, LE1 9BH (United Kingdom); Ikemura, Noriaki; Inoue, Kiyoshi; Miyataka, Hideki; Himeno, Seiichiro [Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770–8514 (Japan); Hossain, Khaled, E-mail: khossain69@yahoo.com [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi-6205 (Bangladesh)

    2012-03-01

    Chronic arsenic (As) exposure affects the endothelial system causing several diseases. Big endothelin-1 (Big ET-1), the biological precursor of endothelin-1 (ET-1) is a more accurate indicator of the degree of activation of the endothelial system. Effect of As exposure on the plasma Big ET-1 levels and its physiological implications have not yet been documented. We evaluated plasma Big ET-1 levels and their relation to hypertension and skin lesions in As exposed individuals in Bangladesh. A total of 304 study subjects from the As-endemic and non-endemic areas in Bangladesh were recruited for this study. As concentrations in water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The plasma Big ET-1 levels were measured using a one-step sandwich enzyme immunoassay kit. Significant increase in Big ET-1 levels were observed with the increasing concentrations of As in drinking water, hair and nails. Further, before and after adjusting with different covariates, plasma Big ET-1 levels were found to be significantly associated with the water, hair and nail As concentrations of the study subjects. Big ET-1 levels were also higher in the higher exposure groups compared to the lowest (reference) group. Interestingly, we observed that Big ET-1 levels were significantly higher in the hypertensive and skin lesion groups compared to the normotensive and without skin lesion counterpart, respectively of the study subjects in As-endemic areas. Thus, this study demonstrated a novel dose–response relationship between As exposure and plasma Big ET-1 levels indicating the possible involvement of plasma Big ET-1 levels in As-induced hypertension and skin lesions. -- Highlights: ► Plasma Big ET-1 is an indicator of endothelial damage. ► Plasma Big ET-1 level increases dose-dependently in arsenic exposed individuals. ► Study subjects in arsenic-endemic areas with hypertension have elevated Big ET-1 levels. ► Study subjects with arsenic-induced

  7. Plasma Endothelin-1 Levels in Preterm Neonatal Infants with Acute Respiratory Failure

    Directory of Open Access Journals (Sweden)

    D. V. Dmitriyev

    2008-01-01

    Full Text Available Increased pulmonary vascular resistance in preterm infants is associated with acute respiratory failure (ARF and at the same time endothelin-1 (E-1 plays an important role in neonatal pulmonary vascular responsiveness. Methods. Endothelin-1 levels were measured in two blood samples in 12 preterm infants with ARF and in 12 controls (at 32.2±1.3 and 29.8±1.2 weeks of gestation, respectively by enzyme immunoassay. For this, the first and second blood samples were taken at 18 to 40 hours after birth. Results. The plasma level of E-1 in the first sample did not differ between the neonates of both groups. In the second sample, significantly higher E-1 concentrations were observed in the newborns with ARF than in the controls. In the first sample, E-1 concentration were higher than in the second one in both groups (p<0.001. There was a significant positive correlation between the second E-1 sample and the SNAPPE 2 scale rating (r=0.38; p=0.02. The plasma level of E-1 in the first sample did not differ in both groups (11.9 and 12.2 pg/ml, respectively. Conclusion. Neonates with and without ARF had the similar plasma E-1 levels in the first sample, by taking into account the fact that the E-1 levels were higher in ARF than in the controls at 18 to 40 hour after birth. Increased vascular resistance in ARF may be associated with the high level of E-1. Key words: endothe-lin-1, acute respiratory failure.

  8. Plasma Interleukin-8 and Endothelin-1 in Symptomatic and Asymptomatic Children

    International Nuclear Information System (INIS)

    Radwan, Z.; El-Abiad, N.; Soliman, M. S.; Ali, A.I.; Ali, G.S.

    2004-01-01

    This study was designed to evaluate the extent to which IL-8 and endothelin-1 are involved in the development of acute exacerbation of atopic asthma. Two asthmatic groups, each of 20 patients were studied, the asymptomatic group where patients were free of symptoms and the symptomatic group where patients were suffering from acute exacerbation of their asthma. Both of asthmatic groups were subclassified into mild and moderate subgroups, each of 10 patients according to the asthma severity. All subjects were subjected to chest X-ray and peak expiratory flow rate (PEFR) recording for sub-classification of patients, skin prick testing using common allergens (patients only) for the identification of atopic asthmatic patients and laboratory investigations including complete blood count (CBC), absolute eosi-nophil count (AEC), urine and stool exam-ination, total serum 1 gE level, plasma inter-leukin-8 (IL-8) level and plasma endothelin-1 (ET-1) level. The data obtained revealed non-significant differences between the studied groups as regards AEC, while serum total 1 gE of the asthmatic groups showed highly significant elevations in comparison to control group. Also, There were highly significant elevations in plasma endothelin-1 and plasma IL-8 levels of the symptomatic asthmatic subgroups in comparison to control group and asymptomatic asthmatic subgroups in comparison to control group and asymptomatic asthmatic subgroups. In conclusion: although it is clear now that IL-8 and ET-1 are involved in acute exacerbation of atopic asthmatic patients, a causal link between those mediators and development of the exacerbation has not been definitively established. Surely, those mediators, their receptors, synthesis and degradation pathways offer potentially important therapeutic targets

  9. Cooperation of endothelin-1 signaling with melanosomes plays a role in developing and/or maintaining human skin hyperpigmentation

    Directory of Open Access Journals (Sweden)

    Daiki Murase

    2015-10-01

    Full Text Available Skin hyperpigmentation is characterized by increased melanin synthesis and deposition that can cause significant psychosocial and psychological distress. Although several cytokine-receptor signaling cascades contribute to the formation of ultraviolet B-induced cutaneous hyperpigmentation, their possible involvement in other types of skin hyperpigmentation has never been clearly addressed. Since our continuous studies using skin specimens from more than 30 subjects with ethnic skin diversity emphasized a consistent augmentation in the expression of endothelin-1 (ET-1 and its receptor (Endothelin B receptor, ET-B in hyperpigmented lesions, including senile lentigos (SLs, the precise function of ET-1 signaling was investigated in the present study. In line with previous studies, ET-1 significantly induced melanogenesis followed by increases in melanosome transport in melanocytes and in its transfer to keratinocytes while inhibition of ET-B function substantially depressed melanogenic ability in tissue-cultured SLs. Additionally, in agreement with a previous report that the formation of autophagosomes rather than melanosomes is stimulated according to starvation or defective melanosome production, ET-1 was found to remarkably augment the expression of components necessary for early melanosome formation, indicating its counteraction against autophagy-targeting melanosome degradation in melanocytes. Despite the lack of substantial impact of ET-1 on keratinocyte melanogenic functions, the expression of ET-1 was enhanced following melanosome uptake by keratinocytes. Taken together, our data suggest that ET-1 plays a substantial role in the development and/or maintenance of skin hyperpigmentation in reciprocal cooperation with increased melanosome incorporation.

  10. The inhibition of the potassium channel TASK-1 in rat cardiac muscle by endothelin-1 is mediated by phospholipase C.

    Science.gov (United States)

    Schiekel, Julia; Lindner, Moritz; Hetzel, Andrea; Wemhöner, Konstantin; Renigunta, Vijay; Schlichthörl, Günter; Decher, Niels; Oliver, Dominik; Daut, Jürgen

    2013-01-01

    The two-pore-domain potassium channel TASK-1 is robustly inhibited by the activation of receptors coupled to the Gα(q) subgroup of G-proteins, but the signal transduction pathway is still unclear. We have studied the mechanisms by which endothelin receptors inhibit the current carried by TASK-1 channels (I(TASK)) in cardiomyocytes. Patch-clamp measurements were carried out in isolated rat cardiomyocytes. I(TASK) was identified by extracellular acidification to pH 6.0 and by the application of the TASK-1 blockers A293 and A1899. Endothelin-1 completely inhibited I(TASK) with an EC(50) of Application of 20 nM endothelin-1 caused a significant increase in action potential duration under control conditions; this was significantly reduced after pre-incubation of the cardiomyocytes with 200 nM A1899. The inhibition of I(TASK) by endothelin-1 was not affected by inhibitors of protein kinase C or rho kinase, but was strongly reduced by U73122, an inhibitor of phospholipase C (PLC). The ability of endothelin-1 to activate PLC-mediated signalling pathways was examined in mammalian cells transfected with TASK-1 and the endothelin-A receptor using patch-clamp measurements and total internal reflection microscopy. U73122 prevented the inhibition of I(TASK) by endothelin-1 and blocked PLC-mediated signalling, as verified with a fluorescent probe for phosphatidylinositol-(4,5)-bisphosphate hydrolysis. Our results show that I(TASK) in rat cardiomyocytes is controlled by endothelin-1 and suggest that the inhibition of TASK-1 via endothelin receptors is mediated by the activation of PLC. The prolongation of the action potential observed with 20 nM endothelin-1 was mainly due to the inhibition of I(TASK).

  11. The Association of Endothelin-1 Signaling with Bone Alkaline Phosphatase Expression and Protumorigenic Activities in Canine Osteosarcoma.

    Science.gov (United States)

    Neumann, Z L; Pondenis, H C; Masyr, A; Byrum, M L; Wycislo, K L; Fan, T M

    2015-01-01

    Canine osteosarcoma (OS) is an aggressive sarcoma characterized by pathologic skeletal resorption and pulmonary metastases. A number of negative prognostic factors, including bone alkaline phosphatase, have been identified in dogs with OS, but the underlying biologic factors responsible for such observations have not been thoroughly investigated. Endothelin-1-mediated signaling is active during bone repair, and is responsible for osteoblast migration, survival, proliferation, and bone alkaline phosphatase expression. The endothelin-1 signaling axis is active in canine OS cells, and this pathway is utilized by malignant osteoblasts for promoting cellular migration, survival, proliferation, and bone alkaline phosphatase activities. 45 dogs with appendicular OS. The expressions of endothelin-1 and endothelin A receptor were studied in OS cell lines and in samples from spontaneously occurring tumors. Activities mediated by endothelin-1 signaling were investigated by characterizing responses in 3 OS cell lines. In 45 dogs with OS, bone alkaline phosphatase concentrations were correlated with primary tumor osteoproductivity. Canine OS cells express endothelin-1 and endothelin A receptor, and this signaling axis mediates OS migration, survival, proliferation, and bone alkaline phosphatase activities. In OS-bearing dogs, circulating bone alkaline phosphatase activities were positively correlated with primary tumor relative bone mineral densities. Canine OS cells express endothelin-1 and functional endothelin A receptors, with the potential for a protumorigenic signaling loop. Increases in bone alkaline phosphatase activity are associated with osteoblastic OS lesions, and might be an epiphenomenon of active endothelin-1 signaling or excessive osteoproduction within the localized bone microenvironment. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  12. Endothelin-1 promotes epithelial–mesenchymal transition in human chondrosarcoma cells by repressing miR-300

    Science.gov (United States)

    Wu, Min-Huan; Huang, Pei-Han; Hsieh, Mingli; Tsai, Chun-Hao; Chen, Hsien-Te; Tang, Chih-Hsin

    2016-01-01

    Chondrosarcoma is a malignant tumor of mesenchymal origin predominantly composed of cartilage-producing cells. This type of bone cancer is extremely resistant to radiotherapy and chemotherapy. Surgical resection is the primary treatment, but is often difficult and not always practical for metastatic disease, so more effective treatments are needed. In particular, it would be helpful to identify molecular markers as targets for therapeutic intervention. Endothelin-1 (ET-1), a potent vasoconstrictor, has been shown to enhance chondrosarcoma angiogenesis and metastasis. We report that ET-1 promotes epithelial–mesenchymal transition (EMT) in human chondrosarcoma cells. EMT is a key pathological event in cancer progression, during which epithelial cells lose their junctions and apical-basal polarity and adopt an invasive phenotype. Our study verifies that ET-1 induces the EMT phenotype in chondrosarcoma cells via the AMP-activated protein kinase (AMPK) pathway. In addition, we show that ET-1 increases EMT by repressing miR-300, which plays an important role in EMT-enhanced tumor metastasis. We also show that miR-300 directly targets Twist, which in turn results in a negative regulation of EMT. We found a highly positive correlation between ET-1 and Twist expression levels as well as tumor stage in chondrosarcoma patient specimens. Therefore, ET-1 may represent a potential novel molecular therapeutic target in chondrosarcoma metastasis. PMID:27602960

  13. Endothelin-1 promotes epithelial-mesenchymal transition in human chondrosarcoma cells by repressing miR-300.

    Science.gov (United States)

    Wu, Min-Huan; Huang, Pei-Han; Hsieh, Mingli; Tsai, Chun-Hao; Chen, Hsien-Te; Tang, Chih-Hsin

    2016-10-25

    Chondrosarcoma is a malignant tumor of mesenchymal origin predominantly composed of cartilage-producing cells. This type of bone cancer is extremely resistant to radiotherapy and chemotherapy. Surgical resection is the primary treatment, but is often difficult and not always practical for metastatic disease, so more effective treatments are needed. In particular, it would be helpful to identify molecular markers as targets for therapeutic intervention. Endothelin-1 (ET-1), a potent vasoconstrictor, has been shown to enhance chondrosarcoma angiogenesis and metastasis. We report that ET-1 promotes epithelial-mesenchymal transition (EMT) in human chondrosarcoma cells. EMT is a key pathological event in cancer progression, during which epithelial cells lose their junctions and apical-basal polarity and adopt an invasive phenotype. Our study verifies that ET-1 induces the EMT phenotype in chondrosarcoma cells via the AMP-activated protein kinase (AMPK) pathway. In addition, we show that ET-1 increases EMT by repressing miR-300, which plays an important role in EMT-enhanced tumor metastasis. We also show that miR-300 directly targets Twist, which in turn results in a negative regulation of EMT. We found a highly positive correlation between ET-1 and Twist expression levels as well as tumor stage in chondrosarcoma patient specimens. Therefore, ET-1 may represent a potential novel molecular therapeutic target in chondrosarcoma metastasis.

  14. The spreading of focal brain edema induced by ultraviolet irradiation

    International Nuclear Information System (INIS)

    Ferszt, R.; Neu, S.; Cervos-Navarro, J.; Sperner, J.

    1978-01-01

    Focal brain edema limited to one cerebral hemisphere was produced by ultraviolet irradiation of the exposed cortex. Tissue water content was determined by the gravimetric method which allows microsampling. Therefore, the spread of edema around the small necrotic area be mapped more precisely than by determination of dry weight which calls for larger samples. As early as 30 min after irradiation, hyperemia and swelling of the brain are observed under the operating microscope. This correlates with venous stasis, hyperemia, and broadened perivascular spaces around venules and large capillaries accompanied by a marked rise in the specific weigth of the tissue. After 4h an edema front can be observed spreading from the perinerotic zone in which there is a marked rise in endothelial cell vesicular activity. Edema reaches maximum levels in the deep white matter at 48h post irradiation with normalisation of the tissue water content after 96h. The velocity at which the edema front spreads from the cortex to the periventricular area lies in the range of 0.25mm/h. Edema reabsorption coincides with signs of retrograde micropinocytosis in endothelial cells. (orig./AJ) [de

  15. Spreading of focal brain edema induced by ultraviolet irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ferszt, R; Neu, S; Cervos-Navarro, J; Sperner, J [Freie Univ. Berlin (Germany, F.R.). Inst. fuer Neuropathologie

    1978-01-01

    Focal brain edema limited to one cerebral hemisphere was produced by ultraviolet irradiation of the exposed cortex. Tissue water content was determined by the gravimetric method which allows microsampling. Therefore, the spread of edema around the small necrotic area be mapped more precisely than by determination of dry weight which calls for larger samples. As early as 30 min after irradiation, hyperemia and swelling of the brain are observed under the operating microscope. This correlates with venous stasis, hyperemia, and broadened perivascular spaces around venules and large capillaries accompanied by a marked rise in the specific weigth of the tissue. After 4h an edema front can be observed spreading from the perinerotic zone in which there is a marked rise in endothelial cell vesicular activity. Edema reaches maximum levels in the deep white matter at 48h post irradiation with normalisation of the tissue water content after 96h. The velocity at which the edema front spreads from the cortex to the periventricular area lies in the range of 0.25mm/h. Edema reabsorption coincides with signs of retrograde micropinocytosis in endothelial cells.

  16. Low levels of plasma endothelin-1 in patients with retinitis pigmentosa

    Directory of Open Access Journals (Sweden)

    Hiroshi Ohguro

    2010-06-01

    Full Text Available Hiroshi Ohguro1, Yukihiko Mashima2, Mitsuru Nakazawa31Department of Ophthalmology, Sapporo Medical University School of Medicine, 2Department of Ophthalmology, Keio University School of Medicine, 3Department of Ophthalmology, Hirosaki University School of Medicine, JapanPurpose: The aim of this study was to elucidate the role of endothelin-1 (ET-1 in the pathophysiology of retinitis pigmentosa (RP.Methods: Plasma ET-1 levels and ophthalmic features in 50 RP patients were compared with those in 20 healthy-eye control subjects. Plasma ET-1 concentrations were determined using a commercially available enzyme-linked immunosorbent assay kit.Results: Mean plasma ET-1 levels of RP patients (1.88 ± 0.56 pg/mL were significantly lower than those of control subjects (2.30 ± 0.30 pg/mL, Mann-Whitney’s U test; P < 0.01. However, ET-1 concentrations varied markedly in each patient. Among RP patients, a significant correlation of ET-1 concentrations was not observed in terms of its hereditary forms or other clinical factors.Conclusion: ET-1 may be important in the pathogenesis of RP, and measurement of its plasma concentrations may also contribute to additional insights into the retinal hemodynamics of RP.Keywords: endothelin-1, retinitis pigmentosa, retinal hemodynamics

  17. Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognition in urban children.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Franco-Lira, Maricela; Cross, Janet V; Engle, Randall; Aragón-Flores, Mariana; Gómez-Garza, Gilberto; Jewells, Valerie; Medina-Cortina, Humberto; Solorio, Edelmira; Chao, Chih-Kai; Zhu, Hongtu; Mukherjee, Partha S; Ferreira-Azevedo, Lara; Torres-Jardón, Ricardo; D'Angiulli, Amedeo

    2013-01-01

    Air pollution exposures are linked to systemic inflammation, cardiovascular and respiratory morbidity and mortality, neuroinflammation and neuropathology in young urbanites. In particular, most Mexico City Metropolitan Area (MCMA) children exhibit subtle cognitive deficits, and neuropathology studies show 40% of them exhibiting frontal tau hyperphosphorylation and 51% amyloid-β diffuse plaques (compared to 0% in low pollution control children). We assessed whether a short cocoa intervention can be effective in decreasing plasma endothelin 1 (ET-1) and/or inflammatory mediators in MCMA children. Thirty gram of dark cocoa with 680 mg of total flavonols were given daily for 10.11 ± 3.4 days (range 9-24 days) to 18 children (10.55 years, SD = 1.45; 11F/7M). Key metabolite ratios in frontal white matter and in hippocampus pre and during cocoa intervention were quantified by magnetic resonance spectroscopy. ET-1 significantly decreased after cocoa treatment (p = 0.0002). Fifteen children (83%) showed a marginally significant individual improvement in one or both of the applied simple short memory tasks. Endothelial dysfunction is a key feature of exposure to particulate matter (PM) and decreased endothelin-1 bioavailability is likely useful for brain function in the context of air pollution. Our findings suggest that cocoa interventions may be critical for early implementation of neuroprotection of highly exposed urban children. Multi-domain nutraceutical interventions could limit the risk for endothelial dysfunction, cerebral hypoperfusion, neuroinflammation, cognitive deficits, structural volumetric detrimental brain effects, and the early development of the neuropathological hallmarks of Alzheimer's and Parkinson's diseases.

  18. The emerging role of endothelin-1 in the pathogenesis of pre-eclampsia.

    Science.gov (United States)

    Saleh, Langeza; Verdonk, Koen; Visser, Willy; van den Meiracker, Anton H; Danser, A H Jan

    2016-10-01

    Pre-eclampsia (PE) is the most frequently encountered medical complication during pregnancy. It is characterized by a rise in systemic vascular resistance with a relatively low cardiac output and hypovolemia, combined with severe proteinuria. Despite the hypovolemia, renin-angiotensin system (RAS) activity is suppressed and aldosterone levels are decreased to the same degree as renin. This suggests that the RAS is not the cause of the hypertension in PE, but rather that its suppression is the consequence of the rise in blood pressure. Abnormal placentation early in pregnancy is widely assumed to be an important initial event in the onset of PE. Eventually, this results in the release of anti-angiogenic factors [in particular, soluble Fms-like tyrosine kinase-1 (sFlt-1)] and cytokines, leading to generalized vascular dysfunction. Elevated sFlt-1 levels bind and inactivate vascular endothelial growth factor (VEGF). Of interest, VEGF inhibition with drugs like sunitinib, applied in cancer patients, results in a PE-like syndrome, characterized by hypertension, proteinuria and renal toxicity. Both in cancer patients treated with sunitinib and in pregnant women with PE, significant rises in endothelin-1 occur. Multiple regression analysis revealed that endothelin-1 is an independent determinant of the hypertension and proteinuria in PE, and additionally a renin suppressor. Moreover, studies in animal models representative of PE, have shown that endothelin receptor blockers prevent the development of this disease. Similarly, endothelin receptor blockers are protective during sunitinib treatment. Taken together, activation of the endothelin system emerges as an important pathway causing the clinical manifestations of PE. This paper critically addresses this concept, taking into consideration both clinical and preclinical data, and simultaneously discusses the therapeutic consequences of this observation. © The Author(s), 2016.

  19. Efecto de la endotelina-1 sobre las arterias tumorales de pacientes con neoplasia colorrectal Effect of endothelin-1 on tumor arteries in patients with colorectal cancer

    Directory of Open Access Journals (Sweden)

    E. Ferrero Herrero

    2008-06-01

    Full Text Available La endotelina-1 es un péptido vasoconstrictor producido por el endotelio vascular, cuyos niveles plasmáticos están aumentados en los pacientes con cáncer colorrectal y que puede participar en la regulación del flujo sanguíneo tumoral. Para estudiar si la respuesta a este péptido está alterada en las arterias tumorales, se obtuvieron, de 13 pacientes intervenidos quirúrgicamente por cáncer colorrectal, arterias mesentéricas irrigando el tumor y arterias mesentéricas de una región alejada del tumor, y asimismo se obtuvieron arterias mesentéricas de pacientes intervenidos por diverticulitis (n = 4 o enfermedad inflamatoria intestinal (n = 3. Las arterias mesentéricas se montaron en una preparación para el registro de la contracción isométrica en un baño de órganos, encontrándose que la endotelina-1 producía contracción en los tres tipos de arterias, pero la sensibilidad a este péptido fue mayor en las arterias irrigando el tumor que en las arterias alejadas del tumor o en las arterias de pacientes sin patología tumoral. Estos resultados indican que la endotelina-1 puede regular el flujo sanguíneo en los tumores colorrectales, produciendo una mayor vasoconstricción en las arterias que irrigan el tumor que en las arterias no tumorales.Endothelin-1 is an endothelium-derived vasoconstrictor peptide whose plasma levels are increased in patients with colorectal cancer, and which may be involved in tumor blood flow regulation. To study whether response to this peptide is altered in tumor arteries, mesenteric arteries supplying blood flow to colorectal tumors, and mesenteric arteries far from said tumors were obtained from 13 patients undergoing colectomy; mesenteric arteries were also obtained from patients with diverticulitis (n = 4 or inflammatory bowel disease (n = 3. Arteries were prepared for isometric tension recording in an organ bath, and in this preparation it was found that endothelin-1 induced contraction in all three

  20. Endothelin-1 activation of ETB receptors leads to a reduced cellular proliferative rate and an increased cellular footprint

    International Nuclear Information System (INIS)

    Wilson, Jamie L.; Taylor, Linda; Polgar, Peter

    2012-01-01

    Endothelin-1 (ET-1) is a vasoactive peptide which signals through two G-protein coupled receptors, endothelin receptor A (ETA) and B (ETB). We determined that ET-1 activation of its ETB receptor in stably cDNA transfected CHO cells leads to a 55% reduction in cell number by end-point cell counting and a 35% decrease in cell growth by a real-time cell-substrate impedance-based assay after 24 h of cell growth. When CHO ETB cells were synchronized in the late G1 cell cycle phase, ET-1 delayed their S phase progression compared to control by 30% as determined by [ 3 H]-thymidine incorporation. On the other hand, no such delay was observed during late G2/M to G1 transit when cells were treated with ET-1 after release from mitotic arrest. Using the cell-substrate impedance-based assay, we observed that ET-1 induces opposing morphological changes in CHO ETA and CHO ETB cells with ETB causing an increase in the cell footprint and ETA a decrease. Likewise, in pulmonary artery smooth muscle cells, which express both ETA and ETB receptors, ET-1 induces an ETA-dependent contraction and an ETB dependent dilation. These results are shedding light on a possible beneficial role for ETB in diseases involving ET-1 dysfunction such as pulmonary hypertension. -- Highlights: ► ET- hinders cell proliferation in CHO cells transfected with ETB. ► ET-1 also decreases the rate of DNA synthesis in CHO ETB cells. ► JNK and PI3K appear to be involved in this reduction of DNA synthesis. ► ETB activation in CHO ETB cells and hSMCs leads to dilatory morphological changes. ► In CHO ETA and hSMCs, ETA activation leads to constrictive morphological changes.

  1. Endothelin-1 activation of ETB receptors leads to a reduced cellular proliferative rate and an increased cellular footprint

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Jamie L.; Taylor, Linda; Polgar, Peter, E-mail: peterp@bu.edu

    2012-06-10

    Endothelin-1 (ET-1) is a vasoactive peptide which signals through two G-protein coupled receptors, endothelin receptor A (ETA) and B (ETB). We determined that ET-1 activation of its ETB receptor in stably cDNA transfected CHO cells leads to a 55% reduction in cell number by end-point cell counting and a 35% decrease in cell growth by a real-time cell-substrate impedance-based assay after 24 h of cell growth. When CHO ETB cells were synchronized in the late G1 cell cycle phase, ET-1 delayed their S phase progression compared to control by 30% as determined by [{sup 3}H]-thymidine incorporation. On the other hand, no such delay was observed during late G2/M to G1 transit when cells were treated with ET-1 after release from mitotic arrest. Using the cell-substrate impedance-based assay, we observed that ET-1 induces opposing morphological changes in CHO ETA and CHO ETB cells with ETB causing an increase in the cell footprint and ETA a decrease. Likewise, in pulmonary artery smooth muscle cells, which express both ETA and ETB receptors, ET-1 induces an ETA-dependent contraction and an ETB dependent dilation. These results are shedding light on a possible beneficial role for ETB in diseases involving ET-1 dysfunction such as pulmonary hypertension. -- Highlights: Black-Right-Pointing-Pointer ET- hinders cell proliferation in CHO cells transfected with ETB. Black-Right-Pointing-Pointer ET-1 also decreases the rate of DNA synthesis in CHO ETB cells. Black-Right-Pointing-Pointer JNK and PI3K appear to be involved in this reduction of DNA synthesis. Black-Right-Pointing-Pointer ETB activation in CHO ETB cells and hSMCs leads to dilatory morphological changes. Black-Right-Pointing-Pointer In CHO ETA and hSMCs, ETA activation leads to constrictive morphological changes.

  2. Plasma endothelin-1 and tumor necrosis factor-alpha concentrations in pregnant and cyclic rats after low-dose endotoxin infusion

    NARCIS (Netherlands)

    Faas, MM; Bakker, WW; Valkhof, N; Baller, JFW; Schuiling, GA

    Plasma endothelin-1 and tumor necrosis factor-alpha were determined in pregnant and cyclic rats after infusion of either endotoxin (1.0 mu g/kg of body weight) or saline solution. After endotoxin, but not after saline solution, administration there was a transient endothelin-1 response in pregnant

  3. Progestins oppose the effects of estradiol on the endothelin-1 receptor type B in coronary arteries from ovariectomized hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Pedersen, Susan H; Nielsen, Lars B; Mortensen, Alicja

    2008-01-01

    OBJECTIVE: Progestins may be associated with the adverse cardiovascular outcomes observed with estrogen plus progestogen therapy, but the mechanism is not resolved. In this study we examined the effect of 17beta-estradiol (E2) alone and in combination with two progestins on the endothelin-1 (ET-1...

  4. Endothelin-1 and -3 plasma concentrations in patients with cirrhosis: role of splanchnic and renal passage and liver function

    DEFF Research Database (Denmark)

    Gerbes, A L; Møller, S; Gülberg, V

    1995-01-01

    of splanchnic and renal passage and of liver function on plasma concentrations of endothelin-1 (ET-1) and endothelin-3 (ET-3) in patients with cirrhosis compared with controls. Eighteen patients with cirrhosis and 8 normotensive controls of similar age were investigated. Arterial and venous plasma samples were...

  5. Nonhuman primate models of focal cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Jingjing Fan

    2017-01-01

    Full Text Available Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.

  6. Myoendothelial coupling in the mesenteric arterial bed; segmental differences and interplay between nitric oxide and endothelin-1

    Science.gov (United States)

    Hilgers, RHP; De Mey, JGR

    2009-01-01

    Background and purpose: We tested the hypothesis that activated arterial smooth muscle (ASM) stimulates endothelial vasomotor influences via gap junctions and that the significance of this myoendothelial coupling increases with decreasing arterial diameter. Experimental approach: From WKY rats, first-, second-, third-and fourth-order branches of the superior mesenteric artery (MA1, MA2, MA3 and MA4 respectively) were isolated and mounted in wire-myographs to record vasomotor responses to 0.16–20 µmol·L−1 phenylephrine. Key results: Removal of endothelium increased the sensitivity (pEC50) to phenylephrine in all arteries. The nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) (100 µmol·L−1) did not modify pEC50 to phenylephrine in all denuded arteries, and increased it in intact MA1, MA2 and MA3 to the same extent as denudation. However, in intact MA4, the effect of L-NAME was significantly larger (ΔpEC50 0.57 ± 0.02) than the effect of endothelium removal (ΔpEC50 0.20 ± 0.06). This endothelium-dependent effect of L-NAME in MA4 was inhibited by (i) steroidal and peptidergic uncouplers of gap junctions; (ii) a low concentration of the NO donor sodium nitroprusside; and (iii) by the endothelin-receptor antagonist bosentan. It was also observed during contractions induced by (i) calcium channel activation (BayK 8644, 0.001–1 µmol·L−1); (ii) depolarization (10–40 mmol·L−1 K+); and (iii) sympathetic nerve stimulation (0.25–32 Hz). Conclusions and implications: These pharmacological observations indicated feedback control by endothelium of ASM reactivity involving gap junctions and a balance between endothelium-derived NO and endothelin-1. This myoendothelial coupling was most prominent in distal resistance arteries. PMID:19302591

  7. Vascular reactivity of mesenteric arteries and veins to endothelin-1 in a murine model of high blood pressure.

    Science.gov (United States)

    Pérez-Rivera, Alex A; Fink, Gregory D; Galligan, James J

    2005-06-01

    We characterized vascular reactivity to endothelin-1 (ET-1) in mesenteric vessels from DOCA-salt hypertensive and SHAM control mice and assessed the effect that endothelial-derived vasodilators have on ET-1-induced vasoconstriction. Changes in the diameter of unpressurized small mesenteric arteries and veins (100- to 300-microm outside diameter) were measured in vitro using computer-assisted video microscopy. Veins were more sensitive than arteries to the contractile effects of ET-1. There was a decrease in arterial maximal responses (E(max)) compared to veins, this effect was larger in DOCA-salt arteries. The selective ET(B) receptor agonist, sarafotoxin 6c (S6c), contracted DOCA-salt and SHAM veins but did not contract arteries. The ET(B) receptor antagonist, BQ-788 (100 nM), but not the ET(A) receptor antagonist, BQ-610 (100 nM), blocked S6c responses. BQ-610 partially inhibited responses to ET-1 in mesenteric veins from DOCA-salt and SHAM mice while BQ-788 did not affect responses to ET-1. Co-administration of both antagonists inhibited responses to ET-1 to a greater extent than BQ-610 alone suggesting a possible functional interaction between ET(A) and ET(B) receptors. Responses to ET-1 in mesenteric arteries were completely inhibited by BQ-610 while BQ-788 did not affect arterial responses. Nitric oxide synthase inhibition potentiated ET-1 responses in veins from SHAM but not DOCA-salt mice. There was a prominent role for ET-mediated nitric oxide release in DOCA-salt but not SHAM arteries. In summary, these studies showed a differential regulation of ET-1 contractile mechanisms between murine mesenteric arteries and veins.

  8. Electroacupuncture pretreatment induces tolerance against focal cerebral ischemia through activation of canonical Notch pathway

    Directory of Open Access Journals (Sweden)

    Zhao Yu

    2012-09-01

    Full Text Available Abstract Background Electroacupuncture (EA pretreatment can induce the tolerance against focal cerebral ischemia. However, the underlying mechanisms have not been fully understood. Emerging evidences suggest that canonical Notch signaling may be involved in ischemic brain injury. In the present study, we tested the hypothesis that EA pretreatment-induced tolerance against focal cerebral ischemia is mediated by Notch signaling. Results EA pretreatment significantly enhanced Notch1, Notch4 and Jag1 gene transcriptions in the striatum, except Notch1 intracellular domain level, which could be increased evidently by ischemia. After ischemia and reperfusion, Hes1 mRNA and Notch1 intracellular domain level in ischemic striatum in EA pretreatment group were increased and reached the peak at 2 h and 24 h, respectively, which were both earlier than the peak achieved in control group. Intraventricular injection with the γ-secretase inhibitor MW167 attenuated the neuroprotective effect of EA pretreatment. Conclusions EA pretreatment induces the tolerance against focal cerebral ischemia through activation of canonical Notch pathway.

  9. Effects of age and caloric restriction in the vascular response of renal arteries to endothelin-1 in rats.

    Science.gov (United States)

    Amor, Sara; García-Villalón, Angel Luis; Rubio, Carmen; Carrascosa, Jose Ma; Monge, Luis; Fernández, Nuria; Martín-Carro, Beatriz; Granado, Miriam

    2017-02-01

    Cardiovascular alterations are the most prevalent cause of impaired physiological function in aged individuals with kidney being one the most affected organs. Aging-induced alterations in renal circulation are associated with a decrease in endothelium-derived relaxing factors such as nitric oxide (NO) and with an increase in contracting factors such as endothelin-1(ET-1). As caloric restriction (CR) exerts beneficial effects preventing some of the aging-induced alterations in cardiovascular system, the aim of this study was to analyze the effects of age and caloric restriction in the vascular response of renal arteries to ET-1 in aged rats. Vascular function was studied in renal arteries from 3-month-old Wistar rats fed ad libitum (3m) and in renal arteries from 8-and 24-month-old Wistar rats fed ad libitum (8m and 24m), or subjected to 20% caloric restriction during their three last months of life (8m-CR and 24m-CR). The contractile response to ET-1 was increased in renal arteries from 8m and 24m compared to 3m rats. ET-1-induced contraction was mediated by ET-A receptors in all experimental groups and also by ET-B receptors in 24m rats. Caloric restriction attenuated the increased contraction to ET-1 in renal arteries from 8m but not from 24m rats possibly through NO release proceeding from ET-B endothelial receptors. In 24m rats, CR did not attenuate the aging-increased response of renal arteries to ET-1, but it prevented the aging-induced increase in iNOS mRNA levels and the aging-induced decrease in eNOS mRNA levels in arterial tissue. In conclusion, aging is associated with an increased response to ET-1 in renal arteries that is prevented by CR in 8m but not in 24m rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. The Matrix Metalloproteases and Endothelin-1 in Infection-Associated Preterm Birth

    Directory of Open Access Journals (Sweden)

    Nicole S. Olgun

    2010-01-01

    Full Text Available Preterm birth (PTB is clinically defined as any delivery which occurs before the completion of 37 weeks of gestation, and is currently the most important problem in obstetrics. In the United States, PTB accounts for 12-13% of all live births, and, with the exception of fetuses suffering from anomalies, is the primary cause of perinatal mortality. While the risk factors for PTB are numerous, the single most common cause is intrauterine infection. As there is currently no FDA-approved therapy for infection-associated PTB, understanding the pathogenesis of preterm labor (PTL and delivery should be given high priority. The matrix metalloproteinases (MMPs are a family of enzymes that have been implicated in normal parturition as well as infection-triggered rupture of membranes and preterm birth. Several lines of evidence also suggest a role for endothelin-1 (ET-1 in infection-associated preterm delivery. This paper focuses on the evidence that the MMPs and ET-1 act in the same molecular pathway in preterm birth.

  11. Homocysteine, endothelin-1 and nitric oxide in patients with hypertensive disorders complicating pregnancy.

    Science.gov (United States)

    Zeng, Yachang; Li, Mujun; Chen, Yue; Wang, Sumei

    2015-01-01

    To investigate the change of level of serum homocysteine (Hcy), endothelin-1 (ET-1) and nitric oxide (NO) and clinical significance in patients with HDCP. Two hundred and thirty nine patients with HDCP (137 patients with mild preeclampsia, 102 patients with severe preeclampsia) who were hospitalized between June 2012 and June 2015 and 200 normal pregnancy women in outpatient department were enrolled in our study were divided into HDCP group and control group. Serum Hcy concentration was measured by enzymatic cycling assay. ET-1 concentration was measured by enzyme linked immunosorbent assay. And no concentration was measured by nitrate reductase assay. Serum Hcy and ET-1 in HDCP group were significantly higher as compared to control group (Ppreclampsia group (P<0.05). Level of serum NO in severe preeclampsia group were significantly lower than in mild preeclampsia group (P<0.05). Spearman rank correlation analysis showed that level of serum Hcy and ET-1 was positively correlated with severity of diseases (r=0.689, 0.718, P<0.05). Level of serum NO was negatively correlated with severity of diseases (r=-0.702, P<0.05). Serum Hcy, ET-1 and NO were associated with pathogenesis of HDCP. Comprehensively measurement of them could effectively evaluate the incidence and progress of HDCP.

  12. Characterization of [125I]endothelin-1 binding sites in rat cardiac membrane fragments

    International Nuclear Information System (INIS)

    Gu, X.H.; Casley, D.J.; Nayler, W.G.

    1989-01-01

    Standard binding and displacement techniques were used to identify high-affinity binding sites for [ 125 I]-labeled endothelin-1 (ET-1) in membranes harvested from the hearts of adult female Sprague-Dawley rats. A single population of binding sites was identified, with a KD of 0.20 +/- 0.03 nM at 37 degrees C, and a Bmax of 93.5 +/- 6.4 fmol/mg protein. Bound [ 125 I]ET-1 was displaced by ET-1 (10(-13)-10(-8) M), with a Ki of 0.08 nM. Neither (-)Bay K 8644 (10(-11)-10(-5) M), prenylamine (10(-11)-10(-5) M), (+)-cis-diltiazem (10(-10)-10(-5) M), (-)D888 (10(-10)-10(-5) M), nicardipine (10(-10)-10(-5) M), lidoflazine (10(-11)-10(-5) M), flunarizine (10(-11)-10(-5) M), omega-conotoxin (10(-13)-10(-7) M), nor prazosin (10(-10)-10(-5) M) displaced the bound ligand. Binding occurred in the absence of Ca2+ and was absent in heat-denatured membranes. These results are interpreted to mean that [ 125 I]ET-1 binds to a single class of high-affinity binding sites that differ from those occupied by known regulators of voltage activated L- and N-type Ca2+ channels

  13. Circulating levels of endothelin-1 in a homogenous Gulf Arab population with untreated essential hypertension.

    Science.gov (United States)

    Obineche, Enyioma; Abdulle, Abdishakur M; Bokhari, Awais M; Yasin, Javed Y; Gillett, Michael P T

    2006-01-01

    Racial variations are reported in the natural history of hypertension. For example, hypertension is significantly more prevalent in blacks than whites. Endothelial cells are important regulators of vascular tone and homeostasis, in part through secretions of vasoactive substances including endothelin-1 (ET-1), a small peptide with potent vasopressor actions. In black hypertensives, ET-1 levels are higher than in normotensive blacks and in both hypertensive and normotensive whites. Since ET-1 might play a significant role in the development and severity of hypertension in the indigenous Arab population of the United Arab Emirates, we investigated the circulating levels of ET-1 in this homogenous population. ET-1 levels were measured in plasma samples from 60 untreated hypertensive Arabs and compared with 60 age- and sex-matched normotensive controls. ET-1 levels were significantly higher in hypertensives (mean 10.1 +/- 1 pmol/L) than normotensives (mean 2.2 +/- 0.5 pmol/L). Body mass index (BMI) was slightly higher among the hypertensives. For all subjects these levels significantly (P Arabs as compared with reported levels in white hypertensives and ET-1 could be a risk factor for cardiovascular diseases in this population. The endothelial system might be particularly important with respect to hypertension in this racial group and merits further study.

  14. Plasmatic endothelin-1 levels in hyperthyroid patients before and after antithyroid therapy.

    Science.gov (United States)

    Cesareo, R; Tarabuso, A; Di Benedetto, M; Lacerna, F; Reda, G

    2000-03-01

    The Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide produced by endothelial cells in many vascular diseases probably as a response to vessel damage. In hyperthyroidism as in other endocrinological diseases elevated ET-1 plasma levels have been found. The effect of antithyroid therapy on ET-1 plasmatic levels was evaluated by measuring ET-1 plasma levels before and 2 and 6 months after treatment with methimazole in 14 patients affected by hyperthyroidism. The hyperthyroid patients had significantly higher ET-1 levels than the controls (18.85 +/- 5.7 vs 10.9 +/- 2.1 pg/ml), while after treatment no difference was found. The ET-1 plasma levels of hyperthyroid patients correlated closely with the raised thyroid metabolic activity independently of its cause. It is possible that the increased ET-1 levels in hyperthyroid patients are the expression of blood vessel damage caused by high thyroid hormone levels. Moreover the results of this study could suggest that, in future, ET-1 plasmatic levels might be considered as a functional thyroid index in hyperthyroid diseases.

  15. Expression of endothelin-1 gene and protein in human granulosa cells

    Energy Technology Data Exchange (ETDEWEB)

    Magini, A.; Granchi, S.; Susini, T. [Univ. of Florence (Italy)] [and others

    1996-04-01

    Previous studies in animal models indicated an autocrine/paracrine action of endothelin-1 (ET-1) in the ovary. We now report evidence on the presence of ET-1 in human ovary during reproductive life. Immunohistochemical and in situ hybridization studies demonstrated a positive signal into cytoplasm of granulosa cells (GC) of follicles at different growth stages. The concentration of ET-1-like immunoreactivity (ET-1-Li) was also measured by a specific RIA in human follicular fluid (FF). FF samples were obtained from women in an in vitro fertilization program undergoing gonadotropin stimulation (group A; n = 24) or no treatment (group B; n = 7). The mean ({+-}SD) ET-1-LI FF level in group A (4.85 {+-} 2.06 pg/mL) was significantly higher than that in group B (1.29 {+-} 0.43 pg/mL; P < 0.01), whereas the corresponding mean plasma levels were not significantly different and were not correlated to respective FF values. Our results indicate for the first time the presence of ET-1 and its messenger ribonucleic acid in the GC of the human ovary. The higher ET-1-LI levels found in the FF from women undergoing gonadotropin treatment suggest a modulation by gonadotropins and/or ovarian steroids of ET-1 production by GC. 19 refs., 4 figs., 1 tab.

  16. Production of flat KrF laser focal profiles with echelon free-induced spatial incoherence

    International Nuclear Information System (INIS)

    Deniz, A.V.; Obenschain, S.P.; Pronko, M.; Lehmberg, R.H.

    1990-01-01

    High gain direct-drive laser fusion requires a uniform spherical pellet implosion. This in turn requires that the focal profile of each driving beam be sufficiently uniform and controlled. Several methods for producing uniform beams have been proposed. One promising technique, echelon free-induced spatial incoherence (ISI), consists of propagating a broadband spatially incoherent beam through an entire laser system. This technique will be used in the Nike laser, which is a twenty-four- to forty-eight-beam multikilojoule KrF system currently under construction at the Naval Research Laboratory (NRL). This paper presents measurements of focal profiles of laser light smoothed by echelon free ISI from a KrF oscillator and amplifier. The initial implementation is shown

  17. Hemin offers neuroprotection through inducing exogenous neuroglobin in focal cerebral hypoxic-ischemia in rats

    Science.gov (United States)

    Song, Xue; Xu, Rui; Xie, Fei; Zhu, Haiyuan; Zhu, Ji; Wang, Xin

    2014-01-01

    Objective: To investigate the inducible effect of hemin on exogenous neuroglobin (Ngb) in focal cerebral hypoxic-ischemia in rats. Methods: 125 healthy SD rats were randomly divided into five groups: sham-operation control group, operation group, hemin treatment group, exogenous Ngb treatment group, and hemin and exogenous Ngb joint treatment group. Twenty-four hours after focal cerebral hypoxic-ischemia, Ngb expression was evaluated by immunocytochemistry, RT-PCR, and western blot analyses, while the brain water content and infarct volume were examined. Results: Immunocytochemistry, RT-PCR, and western blot analyses showed more pronounced Ngb expression in the hemin and exogenous Ngb joint operation group than in the hemin or exogenous Ngb individual treatment groups, thus producing significant differences in brain water content and infarct volume (p exogenous Ngb. PMID:24966924

  18. The role of the biomarker and the genetic polymorphism of endothelin-1 in pulmonary arterial hypertension among Egyptians

    Directory of Open Access Journals (Sweden)

    Emad Ibrahim

    2012-10-01

    Conclusions: In conclusion, our findings suggest a potential link between endothelin-1 level and specific genotypes in the EDN1 gene and susceptibility for PAH with a worse haemodynamic profile. Further investigations are warranted to understand the molecular basis and to confirm the potential clinical importance of these findings on larger cohorts of patients with PAH. This will impact on the management of PAH of Egyptian patients in the near future.

  19. Orphan Nuclear Receptor Nur77 Is a Novel Negative Regulator of Endothelin-1 Expression In Vascular Endothelial Cells

    OpenAIRE

    Qin, Qing; Chen, Ming; Yi, Bing; You, Xiaohua; Yang, Ping; Sun, Jianxin

    2014-01-01

    Endothelin-1 (ET-1) produced by vascular endothelial cells plays essential roles in the regulation of vascular tone and development of cardiovascular diseases. The objective of this study is to identify novel regulators implicated in the regulation of ET-1 expression in vascular endothelial cells (ECs). By using quantitative real-time PCR (qRT-PCR) and Enzyme-linked immunosorbent assay (ELISA), we show that either ectopic expression of orphan nuclear receptor Nur77 or pharmacological activati...

  20. Correlation of Endothelin-1 Concentration and Angiotensin-Converting Enzyme Activity with the Staging of Liver Fibrosis

    OpenAIRE

    Kardum, Duško; Fabijanić, Damir; Lukić, Anita; Romić, Željko; Petrovečki, Mladen; Bogdanović, Zoran; Jurić, Klara; Urek-Crnčević, Marija; Banić, Marko

    2012-01-01

    Increased serum angiotensin-converting enzyme (SACE) activity and serum concentration of endothelin-1 (ET-1) were found in liver cirrhosis. We investigated a correlation between the different stages of liver fibrosis and SACE activity and serum ET-1 concentration. Seventy patients with pathohistologically established chronic liver disease were divided in three groups according to Ishak criteria for liver fibrosis: minimal fibrosis (Ishak score 0–1, n=20), medium fibrosis (Ishak sc...

  1. Increased calcineurin expression after pilocarpine-induced status epilepticus is associated with brain focal edema and astrogliosis.

    Science.gov (United States)

    Liu, Jinzhi; Li, Xiaolin; Chen, Liguang; Xue, Ping; Yang, Qianqian; Wang, Aihua

    2015-07-28

    Calcineurin plays an important role in the development of neuronal excitability, modulation of receptor's function and induction of apoptosis in neurons. It has been established in kindling models that status epilepticus induces brain focal edema and astrocyte activation. However, the role of calcineurin in brain focal edema and astrocyte activation in status epilepticus has not been fully understood. In this study, we employed a model of lithium-pilocarpine-induced status epilepticus and detected calcineurin expression in hippocampus by immunoblotting, brain focal edema by non-invasive magnetic resonance imaging (MRI-7T) and astrocyte expression by immunohistochemistry. We found that the brain focal edema was seen at 24 h after status epilepticus, and astrocyte expression was obviously seen at 7 d after status epilepticus. Meanwhile, calcineurin expression was seen at24 h and retained to 7 d after status epilepticus. A FK506, a calcineurin inhibitor, remarkably suppressed the status epilepticus-induced brain focal edema and astrocyte expression. Our data suggested that calcineurin overexpression plays a very important role in brain focal edema and astrocyte expression. Therefore, calcineurin may be a novel candidate for brain focal edema occurring and intracellular trigger of astrogliosis in status epilepticus.

  2. Correlation of plasma endothelin-1 levels with pulmonary hypertension after inhaled nitric oxide therapy

    International Nuclear Information System (INIS)

    Razzaq, Z.; Naqvi, S.; Aslam, M.

    2009-01-01

    Variable response to inhaled nitric oxide (iNO) therapy in patients with mitral stenosis (MS) having pulmonary hypertension (PH) has been documented in early studies. The objectives of this study were to measure plasma Endothelin-1 (ET-1) levels in those patients and to correlate them with pulmonary vascular indices after iNO therapy. It was Quesi-experimental study. Methods: Thirty patients with mitral or mixed mitral and aortic valve disease with severe pulmonary hypertension and enrolled for valve replacement surgery were included. Before the replacement, baseline pulmonary vascular indices and cardiac output were recorded. After the surgery, 10 - 20 was in administered for 1 hour and all the parameters were again recorded. Patients were grouped into responders and non responders on the basis of % reduction in Pulmonary Vascular Resistance (PVR) after iNO therapy. Plasma ET-1 levels were measured in both groups by ELISA before and after the iNO therapy. Paired sample t-test was used to compare mean values for significance. The correlations between variables were then calculated by using Pearson's coefficient. Results: The plasma ET-1 levels were very high in all patients. They reduced in responders after iNO therapy; non-responders paradoxically showed significant increase in the levels of ET-1 after iNO therapy. Moreover, a positive correlation was observed in plasma ET-1 levels and post operative levels of PVR. Conclusion: The correlation of changes in PVR and plasma ET-1 levels in responders suggests that high plasma ET-1 is a key mediator of poor response in PH secondary to MS, after iNO therapy. (author)

  3. Comparison of Serum Levels of Endothelin-1 in Chronic Periodontitis Patients Before and After Treatment

    Science.gov (United States)

    Varghese, Sheeja S; Sankari, M.; Jayakumar, ND.

    2017-01-01

    Introduction Endothelin-1 (ET-1) is a potent vasoconstrictive peptide with multi functional activity in various systemic diseases. Previous studies indicate the detection of ET-1 in gingival tissues and gingival crevicular fluid. Aim The aim of this study was to estimate the serum ET-1 levels in clinically healthy subjects and subjects with chronic periodontitis, before and after treatment, and correlate it with the clinical parameters. Materials and Methods A total of 44 patients were included in the study. Group I comprised of 20 subjects with clinically healthy periodontium. Group II comprised of 24 subjects with chronic periodontitis. Group III comprised of same Group II subjects following periodontal management. Serum samples were collected from the subjects and an Enzyme Linked Immunosorbent Assay (ELISA) was done to estimate the ET-1 levels. The ET-1 levels were then correlated among the three groups with the clinical parameters namely, Plaque Index (PI), Sulcus Bleeding Index (SBI), probing pocket depth, clinical attachment loss and Periodontally Inflamed Surface Area (PISA). The independent t-test and paired t-test were used for comparison of clinical parameters and Pearson’s correlation coefficient test was used for correlating the ET-1 levels. Results ET-1 levels in chronic periodontitis subjects were significantly higher compared to healthy subjects (p<0.001). However, the clinical parameters did not statistically correlate with the ET-1 levels. There was a significant decrease in ET-1 levels following treatment (p<0.001). Conclusion Serum ET-1 is increased in chronic periodontitis and reduces after periodontal therapy. Further studies are required to establish ET-1 as a biomarker for periodontal disease. PMID:28571268

  4. Elevated endothelin-1 (ET-1) levels may contribute to hypoadiponectinemia in childhood obesity.

    Science.gov (United States)

    Nacci, Carmela; Leo, Valentina; De Benedictis, Leonarda; Carratù, Maria Rosaria; Bartolomeo, Nicola; Altomare, Maria; Giordano, Paola; Faienza, Maria Felicia; Montagnani, Monica

    2013-04-01

    Pediatric obesity is associated with endothelial dysfunction and hypoadiponectinemia, but the relationship between these two conditions remains to be fully clarified. Whether enhanced release of endothelin-1 (ET-1) may directly impair adiponectin (Ad) production in obese children is not known. The aim of the study was to explore whether and how high circulating levels of ET-1 may contribute to impair Ad production, release, and vascular activity. Sixty children were included into obese (Ob; n = 30), overweight (OW; n = 11), and lean (n = 19) groups. Total and high-molecular-weight Ad, ET-1, vascular cell adhesion molecule-1, and von Willebrand factor levels were measured in serum samples. Adipocytes were stimulated with exogenous ET-1 or with sera from lean, OW, and Ob, and Ad production and release measured in the absence or in the presence of ETA (BQ-123) and ETB (BQ-788) receptor blockers, p42/44 MAPK inhibitor PD-98059, or c-Jun NH2-terminal protein kinase inhibitor SP-600125. Vasodilation to Ad was evaluated in rat isolated arteries in the absence or in the presence of BQ-123/788. Total and high-molecular-weight Ad was significantly decreased and ET-1 levels significantly increased in OW (P ET-1. Exposure of adipocytes to exogenous ET-1 or serum from OW and Ob significantly decreased Ad mRNA and protein levels (P ET-1 on Ad was reverted by BQ-123/788 or PD-98059 but not SP-600125. Ad-mediated vasodilation was further increased in arteries pretreated with BQ-123/788. ET-1-mediated inhibition of Ad synthesis via p42/44 MAPK signaling may provide a possible explanation for hypoadiponectinemia in pediatric obesity and contribute to the development of cardiovascular complications.

  5. Exercise capacity is associated with endothelin-1 release during emotional excitement in coronary artery disease patients.

    Science.gov (United States)

    Tulppo, Mikko P; Piira, Olli-Pekka; Hautala, Arto J; Kiviniemi, Antti M; Miettinen, Johanna A; Huikuri, Heikki V

    2014-08-01

    Endothelin-1 (ET-1), a potent vasoconstrictor, IL-6, and catecholamines are increased and heart rate variability [SD of normal to normal R-R intervals (SDNN)] decreased during emotional excitement, but individual responses vary. We tested the hypothesis that exercise capacity is associated with physiological responses caused by real-life emotional excitement. We measured the plasma levels of ET-1, IL-6, catecholamines, heart rate, and SDNN in enthusiastic male ice hockey spectators (n = 51; age, 59 ± 9 years) with stable coronary artery disease (CAD) at baseline and during the Finnish National Ice Hockey League's final play-off matches. Maximal exercise capacity (METs) by bicycle exercise test and left ventricular ejection fraction (LVEF) were measured on a separate day. ET-1 response from baseline to emotional excitement correlated with maximal METs (r = -0.30; P = 0.040). In a linear stepwise regression analysis age, body mass index (BMI), METs, LVEF, basal ET-1, and subjective experience of excitement were entered the model as independent variables to explain ET-1 response. This model explained 27% of ET-1 response (P = 0.003). Maximal METs were most strongly correlated with ET-1 response (β = -0.45; partial correlation r = -0.43; P = 0.002), followed by BMI (β = -0.31; partial correlation r = -0.31; P = 0.033) and LVEF (β = -0.30; partial correlation r = -0.33; P = 0.023). Exercise capacity may protect against further cardiovascular events in CAD patients, because it is associated with reduced ET-1 release during emotional excitement. Copyright © 2014 the American Physiological Society.

  6. Endothelin-1 stimulates catalase activity through the PKCδ mediated phosphorylation of Serine 167

    Science.gov (United States)

    Rafikov, Ruslan; Kumar, Sanjiv; Aggarwal, Saurabh; Hou, Yali; Kangath, Archana; Pardo, Daniel; Fineman, Jeffrey R.; Black, Stephen M.

    2013-01-01

    Our previous studies have shown that endothelin-1 (ET-1) stimulates catalase activity in endothelial cells and lambs with acute increases in pulmonary blood flow (PBF), without altering gene expression. The purpose of this study was to investigate the molecular mechanism by which this occurs. Exposing pulmonary arterial endothelial cells (PAEC) to ET-1 increased catalase activity and decreased cellular hydrogen peroxide (H2O2) levels. These changes correlated with an increase in serine phosphorylated catalase. Using the inhibitory peptide δV1.1, this phosphorylation was shown to be PKCδ dependent. Mass spectrometry identified serine167 as the phosphorylation site. Site-directed mutagenesis was used to generate a phospho-mimic (S167D) catalase. Activity assays using recombinant protein purified from E.coli or transiently transfected COS-7 cells, demonstrated that S167D-catalase had an increased ability to degrade H2O2 compared to the wildtype enzyme. Using a phospho-specific antibody, we were able to verify that pS167 catalase levels are modulated in lambs with acute increases in PBF in the presence and absence of the ET receptor antagonist, tezosentan. S167 is being located on the dimeric interface suggesting it could be involved in regulating the formation of catalase tetramers. To evaluate this possibility we utilized analytical gel-filtration to examine the multimeric structure of recombinant wildtype- and S167D-catalase. We found that recombinant wildtype catalase was present as a mixture of monomers and dimers while S167D catalase was primarily tetrameric. Further, the incubation of wildtype catalase with PKCδ was sufficient to convert wildtype catalase into a tetrameric structure. In conclusion, this is the first report indicating that the phosphorylation of catalase regulates its multimeric structure and activity. PMID:24211614

  7. Inhibitory effect of rhynchophylline on contraction of cerebral arterioles to endothelin 1: role of rho kinase.

    Science.gov (United States)

    Hao, Hui-Feng; Liu, Li-Mei; Liu, Yu-Ying; Liu, Juan; Yan, Li; Pan, Chun-Shui; Wang, Ming-Xia; Wang, Chuan-She; Fan, Jing-Yu; Gao, Yuan-Sheng; Han, Jing-Yan

    2014-08-08

    Rhynchophylline (Rhy) is a major ingredient of Uncaria rhynchophylla (UR) used to reduce blood pressure and ameliorate brain ailments. This study was to examine the role of Rho kinase (ROCK) in the inhibition of Rhy on contraction of cerebral arterioles caused by endothelin 1 (ET-1). Cerebral arterioles of male Wistar rats were constricted with ET-1 for 10 min followed by perfusion of Rhy for 20 min. Changes in the diameters of the arterioles were recorded. The effects of Rhy on contraction of middle cerebral arteries (MCAs) were determined by a Multi-Myograph. Western blotting and immunofluorescent staining were used to examine the effects of Rhy on RhoA translocation and myosin phosphatase target subunit 1 (MYPT1) phosphorylation. In vivo, Rhy (30-300 µM) relaxed cerebral arterioles constricted with ET-1 dose-dependently. In vitro, Rhy at lower concentrations (1-100 µM) caused relaxation of rat MCAs constricted with KCl and Bay-K8644 (an agonist of L-type voltage-dependent calcium channels (L-VDCCs)). Rhy at higher concentrations (>100 µM) caused relaxation of rat MCAs constricted with ET-1, which was inhibited by Y27632, a ROCK׳s inhibitor. Western blotting of rat aortas showed that Rhy inhibited RhoA translocation and MYPT1 phosphorylation. Immunofluorescent staining of MCAs confirmed that phosphorylation of MYPT1 caused by ET-1 was inhibited by Rhy. These results demonstrate that Rhy is a potent inhibitor of contraction of cerebral arteries caused by ET-1 in vivo and in vitro. The effect of Rhy was in part mediated by inhibiting RhoA-ROCK signaling. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Correlation between plasma endothelin-1 levels and severity of septic liver failure quantified by maximal liver function capacity (LiMAx test. A prospective study.

    Directory of Open Access Journals (Sweden)

    Magnus F Kaffarnik

    Full Text Available To investigate the relationship between the degree of liver dysfunction, quantified by maximal liver function capacity (LiMAx test and endothelin-1, TNF-α and IL-6 in septic surgical patients.28 septic patients (8 female, 20 male, age range 35-80y were prospectively investigated on a surgical intensive care unit. Liver function, defined by LiMAx test, and measurements of plasma levels of endothelin-1, TNF-α and IL-6 were carried out within the first 24 hours after onset of septic symptoms, followed by day 2, 5 and 10. Patients were divided into 2 groups (group A: LiMAx ≥100 μg/kg/h, moderate liver dysfunction; group B: LiMAx <100 μg/kg/h, severe liver dysfunction for analysis and investigated regarding the correlation between endothelin-1 and the severity of liver failure, quantified by LiMAx test.Group B showed significant higher results for endothelin-1 than patients in group A (P = 0.01, d5; 0.02, d10. For TNF-α, group B revealed higher results than group A, with a significant difference on day 10 (P = 0.005. IL-6 showed a non-significant trend to higher results in group B. The Spearman's rank correlation coefficient revealed a significant correlation between LiMAx and endothelin-1 (-0.434; P <0.001, TNF-α (-0.515; P <0.001 and IL-6 (-0.590; P <0.001.Sepsis-related hepatic dysfunction is associated with elevated plasma levels of endothelin-1, TNF-α and IL-6. Low LiMAx results combined with increased endothelin-1 and TNF-α and a favourable correlation between LiMAx and cytokine values support the findings of a crucial role of Endothelin-1 and TNF-α in development of septic liver failure.

  9. The Role of Phosphoramidon on the Biological Activity of Big Endothelin-1 in the Rat Mesenteric Microcirculation in Vivo

    International Nuclear Information System (INIS)

    Abdelhalim, Mohamed A K

    2008-01-01

    The goal of the present study was to clarify the role of metalloprotease inhibitor phosphoramidon on the effects induced by big endothelin-1 (big ET-1) in the rat mesenteric microcirculation in vivo, through investigating the systemic blood pressure, diameter and blood flow velocity of arterioles and venules of the rat mesentery. For this purpose, the rat mesentery was arranged for in situ intravital microscopic observation under transillumination and separate cumulative injections of big ET-1 and phosphoramidon were infused into the right jugular vein, respectively. In these experiments twenty-five rats (Charles River, 130 - 140 g) were used. The experiments were divided into two groups. In the first group of experiments, cumulative injections of big ET-1 (1000-8000 pmole/kg) were infused through a catheter inserted into the right jugular vein. Each dose of big ET-1 was infused 25 min prior to the infusion of the following dose. Infusion of big ET-1 (1000-8000 pmole/kg) elicited a long-lasting pressor effect. The infusion of low doses of big ET-1 (1000-2000 pmole/kg) elicited a significant (p < 0.05) dose-dependent increase in the microvascular blood flow velocity both in arterioles (20 - 30 ?m) and venules (30 - 50 ?m), and diameters of arterioles and venules exhibited a slight not significant vasodilator effect. The infusion of high doses of big ET-1 (4000-8000 pmole/kg) elicited significant dose-dependant decrease in the blood flow velocity of arterioles and venules, and diameters returned to the control runs. This may be attributed to the gradual conversion of big ET-1 to ET-1, and ET-1 is a potent vasoconstrictor. In the second group of experiments, cumulative injections of phosphoramidon (30 mg/kg /10 min) were administered 10 min prior to the infusion of big ET-1. These findings suggested that phosphoramidon significantly suppressed long-lasting pressor effect, dose-dependent increase, dose-dependent decrease and slow vasodilator effect produced by big ET-1

  10. The angiotensin type 2 receptor agonist Compound 21 elicits cerebroprotection in endothelin-1 induced ischemic stroke

    DEFF Research Database (Denmark)

    Joseph, Jason P; Mecca, Adam P; Regenhardt, Robert W

    2014-01-01

    Evidence indicates that angiotensin II type 2 receptors (AT2R) exert cerebroprotective actions during stroke. A selective non-peptide AT2R agonist, Compound 21 (C21), has been shown to exert beneficial effects in models of cardiac and renal disease, as well as hemorrhagic stroke. Here, we hypothe...

  11. Endothelin-1 Regulation of exercise-induced changes in flow: Dynamic regulation of vascular tone

    NARCIS (Netherlands)

    Rapoport, R.M. (Robert M.); D. Merkus (Daphne)

    2017-01-01

    textabstractAlthough endothelin (ET)-1 is a highly potent vasoconstrictor with considerable efficacy in numerous vascular beds, the role of endogenous ET-1 in the regulation of vascular tone remains unclear. The perspective that ET-1 plays little role in the on-going regulation of vascular tone at

  12. Diet-Induced Ketosis Protects Against Focal Cerebral Ischemia in Mouse.

    Science.gov (United States)

    Xu, Kui; Ye, Lena; Sharma, Katyayini; Jin, Yongming; Harrison, Matthew M; Caldwell, Tylor; Berthiaume, Jessica M; Luo, Yu; LaManna, Joseph C; Puchowicz, Michelle A

    2017-01-01

    Over the past decade we have consistently shown that ketosis is neuroprotective against ischemic insults in rats. We reported that diet-induced ketotic rats had a significant reduction in infarct volume when subjected to middle cerebral artery occlusion (MCAO), and improved survival and recovery after cardiac arrest and resuscitation. The neuroprotective mechanisms of ketosis (via ketogenic diet; KG) include (i) ketones are alternate energy substrates that can restore energy balance when glucose metabolism is deficient and (ii) ketones modulate cell-signalling pathways that are cytoprotective. We investigated the effects of diet-induced ketosis following transient focal cerebral ischemia in mice. The correlation between levels of ketosis and hypoxic inducible factor-1alpha (HIF-1α), AKT (also known as protein kinase B or PKB) and 5' AMP-activated protein kinase (AMPK) were determined. Mice were fed with KG diet or standard lab-chow (STD) diet for 4 weeks. For the MCAO group, mice underwent 60 min of MCAO and total brain infarct volumes were evaluated 48 h after reperfusion. In a separate group of mice, brain tissue metabolites, levels of HIF-1α, phosphorylated AKT (pAKT), and AMPK were measured. After feeding a KG diet, levels of blood ketone bodies (beta-hydroxyburyrate, BHB) were increased. There was a proportional decrease in infarct volumes with increased blood BHB levels (KG vs STD; 4.2 ± 0.6 vs 7.8 ± 2.2 mm 3 , mean ± SEM). A positive correlation was also observed with HIF-1α and pAKT relative to blood BHB levels. Our results showed that chronic ketosis can be induced in mice by KG diet and was neuroprotective against focal cerebral ischemia in a concentration dependent manner. Potential mechanisms include upregulation of cytoprotective pathways such as those associated with HIF-1α, pAKT and AMPK.

  13. The effects of endothelin-1 on the cardiorespiratory physiology of the freshwater trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias).

    Science.gov (United States)

    Perry, S F; Montpetit, C J; McKendry, J; Desforges, P R; Gilmour, K M; Wood, C M; Olson, K R

    2001-11-01

    The aim of the present study was to evaluate the effects of endothelin-l-elicited cardiovascular events on respiratory gas transfer in the freshwater rainbow trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias). In both species, endothelin-1 (666 pmol kg(-1)) caused a rapid (within 4 min) reduction (ca. 30-50 mmHg) in arterial blood partial pressure of O2. The effects of endothelin-1 on arterial blood partial pressure of CO2 were not synchronised with the changes in O2 partial pressure and the responses were markedly different in trout and dogfish. In trout, arterial CO2 partial pressure was increased transiently by approximately 1.0 mmHg but the onset of the response was delayed and occurred 12 min after endothelin-1 injection. In contrast, CO2 partial pressure remained more-or-less constant in dogfish after injection of endothelin-1 and was increased only slightly (approximately 0.1 mmHg) after 60 min. Pre-treatment of trout with bovine carbonic anhydrase (5 mg ml(-1)) eliminated the increase in CO2 partial pressure that was normally observed after endothelin-1 injection. In both species, endothelin-1 injection caused a decrease in arterial blood pH that mirrored the changes in CO2 partial pressure. Endothelin-1 injection was associated with transient (trout) or persistent (dogfish) hyperventilation as indicated by pronounced increases in breathing frequency and amplitude. In trout, arterial blood pressure remained constant or was decreased slightly and was accompanied by a transient increase in systemic resistance, and a temporary reduction in cardiac output. The decrease in cardiac output was caused solely by a reduction in cardiac frequency; cardiac stroke volume was unaffected. In dogfish, arterial blood pressure was lowered by approximately 10 mmHg at 6-10 min after endothelin-1 injection but then was rapidly restored to pre-injection levels. The decrease in arterial blood pressure reflected an increase in branchial vascular resistance (as

  14. Endothelin-1 levels in the pathophysiology of chronic obstructive pulmonary disease and bronchial asthma.

    Science.gov (United States)

    Spiropoulos, K; Trakada, G; Nikolaou, E; Prodromakis, E; Efremidis, G; Pouli, A; Koniavitou, A

    2003-08-01

    Endothelin-1 (ET-1) has been implicated in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). The ET-1 levels are elevated during exacerbations of asthma and COPD in bronchoalveolar lavage, serum, and sputum and fails with treatment of the exacerbations. Hypoxemia stimulates ET-1 secretion. The aim of this study was to examine the serum ET-1 levels in stable asthmatic and COPD patients. We examined 48 COPD and 26 asthmatic patients and 34 normal subjects. We collected arterial samples to measure baseline ET-1 levels in all patients and in the control group, during the day. All the patients underwent formal polysomnography (EEG, ECG, airflow, respiratory muscle movement, oximeter) to detect the presence of nocturnal, nonapneic, and oxyhemoglobin desaturation. Twelve of the COPD patients and six of the asthmatic patients were disqualified because of inadequate sleep or sleep apnea syndrome. Nineteen of the COPD patients desaturated below a baseline sleep saturation of 90% for 5 min or more, reaching a nadir saturation of at least 85%. We collected arterial samples to measure ET-1 levels, 5 min after the first period of desaturation in each of the 19 desaturators COPD patients. None of the 20 asthmatic patients exhibited oxyhemoglobin desaturation during sleep. Baseline arterial ET-1 levels during the day were significantly higher in "desaturators" COPD patients (2.08+/-0.28 pg/ml) compared to "non-desaturators" COPD patients (1.38+/-0.16 pg/ml) (P<0.001) and to asthmatics (0.7+/-0.85 pg/ml) (P<0.001). ET-1 Levels in normal subjects were 1.221+/-0.02 pg/ml. In "desaturators" COPD patients ET-1 levels during the night, 5 min after the first oxyhemoglobin desaturation, were significantly higher (4.28+/-1.10 pg/ml) compared to those during the day (2.08+/-0.28 pg/ml) (P<0.001). A significant negative correlation was observed between ET-1 levels and degree of desaturation during the day (P=0.005, r=0.632) and during the night (P<0.001, r=0

  15. Correlations between plasma endothelin-1 levels and breakthrough pain in patients with cancer

    Directory of Open Access Journals (Sweden)

    Yan XB

    2015-12-01

    Full Text Available Xue-bin Yan, Tuo-chao Peng, Dong Huang Department of Anesthesiologist, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, People’s Republic of China Abstract: Endothelin-1 (ET-1 may be involved in driving pain in patients with advanced cancer. However, a few studies focus on the role of ET-1 in breakthrough pain (BP. The aim of this pivotal study was to explore the correlation between the plasma (ET-1 level and BP intensity. A total of 40 patients were enrolled in the study, and they were divided into two groups: BP group and non-BP group. Moreover, 20 healthy adults were used as the normal control group. Pain intensity was measured using visual analog scale (VAS scores of 1–10. Plasma ET-1 levels were detected by an ET radioimmunoassay kit. Subsequently, the correlation of ET-1 level with the VAS score and cancer types was analyzed by Pearson’s correlation coefficient. The plasma ET-1 level in the BP group (35.31±8.02 pg/mL was higher than that in the non-BP group (29.51±6.78 pg/mL and the normal control group (24.77±10.10 pg/mL, P<0.05. In addition, the VAS score in the BP group (7.45±0.82 was higher than that in the non-BP group (2.80±1.23, P<0.05. The plasma ET-1 level was positively correlated with the VAS score of the BP group (Pearson’s r=0.42. There was no significant correlation between the plasma ET-1 level and VAS score of the non-BP group (Pearson’s r=–0.22 or/and cancer types (P>0.05. The elevated plasma ET-1 levels were positively related to BP, and targeting ET-1 may provide a novel pain-reducing therapeutic treatment in BP. Keywords: visual analog scale, correlation, cancer types, background pain

  16. Neuroprotective effects of curcumin on endothelin-1 mediated cell death in hippocampal neurons.

    Science.gov (United States)

    Stankowska, Dorota L; Krishnamoorthy, Vignesh R; Ellis, Dorette Z; Krishnamoorthy, Raghu R

    2017-06-01

    Alzheimer's disease is a progressive neurodegenerative disease characterized by loss of hippocampal neurons leading to memory deficits and cognitive decline. Studies suggest that levels of the vasoactive peptide endothelin-1 (ET-1) are increased in the brain tissue of Alzheimer's patients. Curcumin, the main ingredient of the spice turmeric, has been shown to have anti-inflammatory, anti-cancer, and neuroprotective effects. However, the mechanisms underlying some of these beneficial effects are not completely understood. The objective of this study was to determine if curcumin could protect hippocampal neurons from ET-1 mediated cell death and examine the involvement of c-Jun in this pathway. Primary hippocampal neurons from rat pups were isolated using a previously published protocol. Viability of the cells was measured by the live/dead assay. Immunoblot and immunohistochemical analyses were performed to analyze c-Jun levels in hippocampal neurons treated with either ET-1 or a combination of ET-1 and curcumin. Apoptotic changes were evaluated by immunoblot detection of cleaved caspase-3, cleaved fodrin, and a caspase 3/7 activation assay. ET-1 treatment produced a 2-fold increase in the levels of c-Jun as determined by an immunoblot analysis in hippocampal neurons. Co-treatment with curcumin significantly attenuated the ET-1 mediated increase in c-Jun levels. ET-1 caused increased neuronal cell death of hippocampal neurons indicated by elevation of cleaved caspase-3, cleaved fodrin and an increased activity of caspases 3 and 7 which was attenuated by co-treatment with curcumin. Blockade of JNK, an upstream effector of c-Jun by specific inhibitor SP600125 did not fully protect from ET-1 mediated activation of pro-apoptotic enzymes in primary hippocampal cells. Our data suggests that one mechanism by which curcumin protects against ET-1-mediated cell death is through blocking an increase in c-Jun levels. Other possible mechanisms include decreasing pro

  17. Inhibitory effect of fentanyl citrate on the release of endothlin-1 induced by bradykinin in melanoma cells.

    Science.gov (United States)

    Andoh, Tsugunobu; Shinohara, Akira; Kuraishi, Yasushi

    2017-02-01

    Our previous study showed that the μ-opioid receptor agonist fentanyl citrate inhibits endothelin-1-and bradykinin-mediated pain responses in mice orthotopically inoculated with melanoma cells. We also demonstrated that bradykinin induces endothelin-1 secretion in melanoma cells. However, the analgesic mechanisms of fentanyl citrate remain unclear. Thus, the present study was conducted to determine whether fentanyl citrate affects bradykinin-induced endothelin-1 secretion in B16-BL6 melanoma cells. The amount of endothelin-1 in the culture medium was measured using an enzyme immunoassay. The expression of endothelin-1, kinin B 2 receptors, and μ-opioid receptors in B16-BL/6 melanoma cells was determined using immunocytochemistry. Fentanyl citrate inhibited bradykinin-induced endothelin-1 secretion. The inhibitory effect of fentanyl citrate on the secretion of endothelin-1 was attenuated by the μ-opioid receptor antagonist naloxone methiodide. The immunoreactivities of endothelin-1, kinin B 2 receptors, and μ-opioid receptors in B16-BL6 melanoma cells were observed. These results suggest that fentanyl citrate regulates bradykinin-induced endothelin-1 secretion through μ-opioid receptors in melanoma cells. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. Effect of breed on plasma endothelin-1 concentration, plasma renin activity, and serum cortisol concentration in healthy dogs

    DEFF Research Database (Denmark)

    Höglund, K.; Lequarré, A.-S.; Ljungvall, I.

    2016-01-01

    BACKGROUND: There are breed differences in several blood variables in healthy dogs. OBJECTIVE: Investigate breed variation in plasma endothelin-1 (ET-1) concentration, plasma renin activity, and serum cortisol concentration. ANIMALS: Five-hundred and thirty-one healthy dogs of 9 breeds examined...... at 5 centers (2-4 breeds/center). METHODS: Prospective observational study. Circulating concentrations of ET-1 and cortisol, and renin activity, were measured using commercially available assays. Absence of organ-related or systemic disease was ensured by thorough clinical investigations, including...

  19. Confirmation of translatability and functionality certifies the dual endothelin1/VEGFsp receptor (DEspR) protein.

    Science.gov (United States)

    Herrera, Victoria L M; Steffen, Martin; Moran, Ann Marie; Tan, Glaiza A; Pasion, Khristine A; Rivera, Keith; Pappin, Darryl J; Ruiz-Opazo, Nelson

    2016-06-14

    In contrast to rat and mouse databases, the NCBI gene database lists the human dual-endothelin1/VEGFsp receptor (DEspR, formerly Dear) as a unitary transcribed pseudogene due to a stop [TGA]-codon at codon#14 in automated DNA and RNA sequences. However, re-analysis is needed given prior single gene studies detected a tryptophan [TGG]-codon#14 by manual Sanger sequencing, demonstrated DEspR translatability and functionality, and since the demonstration of actual non-translatability through expression studies, the standard-of-excellence for pseudogene designation, has not been performed. Re-analysis must meet UNIPROT criteria for demonstration of a protein's existence at the highest (protein) level, which a priori, would override DNA- or RNA-based deductions. To dissect the nucleotide sequence discrepancy, we performed Maxam-Gilbert sequencing and reviewed 727 RNA-seq entries. To comply with the highest level multiple UNIPROT criteria for determining DEspR's existence, we performed various experiments using multiple anti-DEspR monoclonal antibodies (mAbs) targeting distinct DEspR epitopes with one spanning the contested tryptophan [TGG]-codon#14, assessing: (a) DEspR protein expression, (b) predicted full-length protein size, (c) sequence-predicted protein-specific properties beyond codon#14: receptor glycosylation and internalization, (d) protein-partner interactions, and (e) DEspR functionality via DEspR-inhibition effects. Maxam-Gilbert sequencing and some RNA-seq entries demonstrate two guanines, hence a tryptophan [TGG]-codon#14 within a compression site spanning an error-prone compression sequence motif. Western blot analysis using anti-DEspR mAbs targeting distinct DEspR epitopes detect the identical glycosylated 17.5 kDa pull-down protein. Decrease in DEspR-protein size after PNGase-F digest demonstrates post-translational glycosylation, concordant with the consensus-glycosylation site beyond codon#14. Like other small single-transmembrane proteins, mass

  20. Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats.

    Science.gov (United States)

    Glendenning, Michele L; Lovekamp-Swan, Tara; Schreihofer, Derek A

    2008-11-14

    Estrogen is a powerful endogenous and exogenous neuroprotective agent in animal models of brain injury, including focal cerebral ischemia. Although this protection has been demonstrated in several different treatment and injury paradigms, it has not been demonstrated in focal cerebral ischemia induced by intraparenchymal endothelin-1 injection, a model with many advantages over other models of experimental focal ischemia. Reproductively mature female Sprague-Dawley rats were ovariectomized and divided into placebo and estradiol-treated groups. Two weeks later, halothane-anesthetized rats underwent middle cerebral artery (MCA) occlusion by interparenchymal stereotactic injection of the potent vasoconstrictor endothelin 1 (180pmoles/2microl) near the middle cerebral artery. Laser-Doppler flowmetry (LDF) revealed similar reductions in cerebral blood flow in both groups. Animals were behaviorally evaluated before, and 2 days after, stroke induction, and infarct size was evaluated. In agreement with other models, estrogen treatment significantly reduced infarct size evaluated by both TTC and Fluoro-Jade staining and behavioral deficits associated with stroke. Stroke size was significantly correlated with LDF in both groups, suggesting that cranial perfusion measures can enhance success in this model.

  1. PROLACTIN-INDUCED TYROSINE PHOSPHORYLATION, ACTIVATION AND RECEPTOR ASSOCIATION OF FOCAL ADHESION KINASE (FAK) IN MAMMARY EPITHELIAL CELLS

    Science.gov (United States)

    Prolactin-Induced Tyrosine Phosphorylation, Activation and ReceptorAssociation of Focal Adhesion Kinase (FAK) in Mammary Epithelial Cells. Suzanne E. Fenton1 and Lewis G. Sheffield2. 1U.S. Environmental ProtectionAgency, MD-72, Research Triangle Park, NC 27711, and

  2. Copper deficiency induced emphysema is associated with focal adhesion kinase inactivation.

    Directory of Open Access Journals (Sweden)

    Shiro Mizuno

    Full Text Available Copper is an important regulator of hypoxia inducible factor 1 alpha (HIF-1α dependent vascular endothelial growth factor (VEGF expression, and is also required for the activity of lysyl oxidase (LOX to effect matrix protein cross-linking. Cell detachment from the extracellular matrix can induce apoptosis (anoikis via inactivation of focal adhesion kinase (FAK.To examine the molecular mechanisms whereby copper depletion causes the destruction of the normal alveolar architecture via anoikis, Male Sprague-Dawley rats were fed a copper deficient diet for 6 weeks while being treated with the copper chelator, tetrathiomolybdate. Other groups of rats were treated with the inhibitor of auto-phosphorylation of FAK, 1,2,4,5-benzenetetraamine tetrahydrochloride (1,2,4,5-BT or FAK small interfering RNA (siRNA.Copper depletion caused emphysematous changes, decreased HIF-1α activity, and downregulated VEGF expression in the rat lungs. Cleaved caspase-3, caspase-8 and Bcl-2 interacting mediator of cell death (Bim expression was increased, and the phosphorylation of FAK was decreased in copper depleted rat lungs. Administration of 1,2,4,5-BT and FAK siRNA caused emphysematous lung destruction associated with increased expression of cleaved capase-3, caspase-8 and Bim.These data indicate that copper-dependent mechanisms contribute to the pathogenesis of emphysema, which may be associated with decreased HIF-1α and FAK activity in the lung.

  3. Statin-induced focal myositis of the upper extremity. A report of two cases

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, M., E-mail: wagner.radiologie@herzchirurgie.de [Department of Radiology, Herz- und Gefaessklinik GmbH, Salzburger Leite 1, D-97616 Bad Neustadt an der Saale (Germany); Muehldorfer-Fodor, M.; Prommersberger, K.J. [Department of Handsurgery, Herz- und Gefaessklinik GmbH, Bad Neustadt an der Saale (Germany); Schmitt, R. [Department of Radiology, Herz- und Gefaessklinik GmbH, Salzburger Leite 1, D-97616 Bad Neustadt an der Saale (Germany)

    2011-02-15

    Statins are widely used to lower increased cholesterol levels with the aim to prevent major cardiovascular events. However, they bare the risk of myotoxic side effects. We report on two patients with focal weakness and pain in the upper extremities. In both patients, abnormal MRI signal heights in the muscle groups involved were indicative of the final diagnosis of focal myositis during statin therapy.

  4. Statin-induced focal myositis of the upper extremity. A report of two cases

    International Nuclear Information System (INIS)

    Wagner, M.; Muehldorfer-Fodor, M.; Prommersberger, K.J.; Schmitt, R.

    2011-01-01

    Statins are widely used to lower increased cholesterol levels with the aim to prevent major cardiovascular events. However, they bare the risk of myotoxic side effects. We report on two patients with focal weakness and pain in the upper extremities. In both patients, abnormal MRI signal heights in the muscle groups involved were indicative of the final diagnosis of focal myositis during statin therapy.

  5. Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognitive responses in urban children.

    Directory of Open Access Journals (Sweden)

    Lilian eCalderon-Garciduenas

    2013-08-01

    Full Text Available Air pollution exposures are linked to systemic inflammation, cardiovascular and respiratory morbidity and mortality, neuroinflammation and neuropathology in young urbanites. In particular, most Mexico City Metropolitan Area (MCMA children exhibit subtle cognitive deficits, and neuropathology studies show 40% of them exhibiting frontal tau hyperphosphorylation and 51% amyloid-β diffuse plaques (compared to 0% in low pollution control children. We assessed whether a short cocoa intervention can be effective in decreasing plasma endothelin 1 (ET-1 and/or inflammatory mediators in MCMA children. Thirty g of dark cocoa with 680 mg of total flavonols were given daily for 10.11± 3.4 days (range 9 to 24 days to 18 children (10.55yrs, SD =1.45; 11F/7M. Key metabolite ratios in frontal white matter and in hippocampus pre and during cocoa intervention were quantified by magnetic resonance spectroscopy. ET-1 significantly decreased after cocoa treatment (p=0.0002. Fifteen children (83% showed a marginally significant individual improvement in one or both of the applied simple short memory tasks. Endothelial dysfunction is a key feature of exposure to particulate matter and decreased endothelin-1 bioavailability is likely useful for brain function in the context of air pollution. Our findings suggest that cocoa interventions may be critical for early implementation of neuroprotection of highly exposed urban children. Multi-domain nutraceutical interventions could limit the risk for endothelial dysfunction, cerebral hypoperfusion, neuroinflammation, cognitive deficits, structural volumetric detrimental brain effects, and the early development of the neuropathological hallmarks of Alzheimer’s and Parkinson’s diseases.

  6. Brain Natriuretic Peptide, Atrial Natriuretic Peptide and Endothelin-1 response to peak exercise in patients with coronary artery disease and correlation with myocardial perfusion scintigraphy abnormalities

    International Nuclear Information System (INIS)

    Erbas, B.; Ergun, E.; Koray, Z.; Kabakci, G.; Yildirir, A.; Kes, S.

    2002-01-01

    Aim: Plasma Brain Natriuretic Peptide (BNP) has been known as a promising marker of ventricular dysfunction in cardiac patients. There are conflicting reports about its response to exercise testing. Therefore, this study was performed to investigate the exercise induced changes in BNP, Atrial Natriuretic Peptide (ANP) and Endothelin-1 (E) levels and their correlation with perfusion abnormalities on myocardial perfusion scintigraphy (MPS). Materials and Methods: Study group consisted of 35 patients (mean age=53.9+11.8) who underwent MPS with suspicion or diagnosis of coronary artery disease. Plasma levels of BNP, ANP, and E were measured at rest and after symptom-limited ergometry. Patients were divided into two groups according to the presence of perfusion abnormality (i.e. ischemia or infarction) on MPS. Results: BNP, ANP and E levels did not change significantly with exercise, however baseline levels of BNP, ANP levels and peak-exercise level of BNP in patients with perfusion abnormalities were significantly higher. Hypertensive patients with or without perfusion abnormalities had higher baseline BNP, ANP levels, and peak-exercise BNP levels compared to normotensives. BNP levels at rest and after exercise had a significant correlation with age (r=0.57, p=0.04; r=0.58, p=0.04), as well as baseline ANP values (r=0.37, p=0.033). Highest baseline BNP, ANP and exercise BNP levels were observed in patients with infarction. Conclusion: Exercise-testing did not induce significant changes in plasma levels of BNP, ANP and E. Higher BNP levels had correlation with the presence of ischemia, infarction and hypertension, as well as, increasing age

  7. Focal ablation for atrial tachycardia from the double-exit of the Marshall bundle inducing atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Jung Yeon Chin, MD

    2017-08-01

    Full Text Available Atrial fibrillation (AF from the ligament/vein of Marshall (LOM/VOM has previously been described. We report the case of a 23-year-old woman with an antiarrhythmic drug-resistant AF induced by two distinct atrial tachycardias (ATs. Focal ablation of these ATs from the double-exit of the Marshall bundle using a three-dimensional map eliminated AF triggering, even though pulmonary vein electrical isolation is the cornerstone for paroxysmal AF. Such mechanisms are important as triggering factors to plan ablation for paroxysmal AF. Focal ablation for triggering and inducing AF, originating from the double-exit of the Marshall bundle may be effective in eliminating AF in young patients.

  8. Obligatory Role of Intraluminal O2− in Acute Endothelin-1 and Angiotensin II Signaling to Mediate Endothelial Dysfunction and MAPK Activation in Guinea-Pig Hearts

    Directory of Open Access Journals (Sweden)

    Emilia Wojtera

    2014-10-01

    Full Text Available We hypothesized that, due to a cross-talk between cytoplasmic O2−-sources and intraluminally expressed xanthine oxidase (XO, intraluminal O2− is instrumental in mediating intraluminal (endothelial dysfunction and cytosolic (p38 and ERK1/2 MAPKs phosphorylation manifestations of vascular oxidative stress induced by endothelin-1 (ET-1 and angiotensin II (AT-II. Isolated guinea-pig hearts were subjected to 10-min agonist perfusion causing a burst of an intraluminal O2−. ET-1 antagonist, tezosentan, attenuated AT-II-mediated O2−, indicating its partial ET-1 mediation. ET-1 and Ang-T (AT-II + tezosentan triggered intraluminal O2−, endothelial dysfunction, MAPKs and p47phox phosphorylation, and NADPH oxidase (Nox and XO activation. These effects were: (i prevented by blocking PKC (chelerythrine, Nox (apocynin, mitochondrial ATP-dependent K+ channel (5-HD, complex II (TTFA, and XO (allopurinol; (ii mimicked by the activation of Nox (NADH; and mitochondria (diazoxide, 3-NPA and (iii the effects by NADH were prevented by 5-HD, TTFA and chelerythrine, and those by diazoxide and 3-NPA by apocynin and chelerythrine, suggesting that the agonists coactivate Nox and mitochondria, which further amplify their activity via PKC. The effects by ET-1, Ang-T, NADH, diazoxide, and 3-NPA were opposed by blocking intraluminal O2− (SOD and XO, and were mimicked by XO activation (hypoxanthine. Apocynin, TTFA, chelerythrine, and SOD opposed the effects by hypoxanthine. In conclusion, oxidative stress by agonists involves cellular inside-out and outside-in signaling in which Nox-mitochondria-PKC system and XO mutually maintain their activities via the intraluminal O2−.

  9. Blockade of Endothelin-1 Receptor Type B Ameliorates Glucose Intolerance and Insulin Resistance in a Mouse Model of Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Jan Polak

    2018-05-01

    Full Text Available Obstructive sleep apnea (OSA is associated with insulin resistance (IR and glucose intolerance. Elevated endothelin-1 (ET-1 levels have been observed in OSA patients and in mice exposed to intermittent hypoxia (IH. We examined whether pharmacological blockade of type A and type B ET-1 receptors (ETA and ETB would ameliorate glucose intolerance and IR in mice exposed to IH. Subcutaneously implanted pumps delivered BQ-123 (ETA antagonist; 200 nmol/kg/day, BQ-788 (ETB antagonist; 200 nmol/kg/day or vehicle (saline or propyleneglycol [PG] for 14 days in C57BL6/J mice (10/group. During treatment, mice were exposed to IH (decreasing the FiO2 from 20.9% to 6%, 60/h or intermittent air (IA. After IH or IA exposure, insulin (0.5 IU/kg or glucose (1 mg/kg was injected intraperitoneally and plasma glucose determined after injection and area under glucose curve (AUC was calculated. Fourteen-day IH increased fasting glucose levels (122 ± 7 vs. 157 ± 8 mg/dL, PG: 118 ± 6 vs. 139 ± 8; both p < 0.05 and impaired glucose tolerance (AUCglucose: 19,249 ± 1105 vs. 29,124 ± 1444, PG AUCglucose: 18,066 ± 947 vs. 25,135 ± 797; both p < 0.05 in vehicle-treated animals. IH-induced impairments in glucose tolerance were partially ameliorated with BQ-788 treatment (AUCglucose: 21,969 ± 662; p < 0.05. Fourteen-day IH also induced IR (AUCglucose: 7185 ± 401 vs. 8699 ± 401; p < 0.05. Treatment with BQ-788 decreased IR under IA (AUCglucose: 5281 ± 401, p < 0.05 and reduced worsening of IR with IH (AUCglucose: 7302 ± 401, p < 0.05. There was no effect of BQ-123 on IH-induced impairments in glucose tolerance or IR. Our results suggest that ET-1 plays a role in IH-induced impairments in glucose homeostasis.

  10. Radiation-Induced Transient Effects in Near Infrared Focal Plane Arrays

    Science.gov (United States)

    Reed, Robert A.; Pickel, J.; Marshall, P.; Waczynski, A.; McMurray, R.; Gee, G.; Polidan, E.; Johnson, S.; McKeivey, M.; Ennico, K.; hide

    2004-01-01

    This viewgraph presentation describes a test simulate the transient effects of cosmic ray impacts on near infrared focal plane arrays. The objectives of the test are to: 1) Characterize proton single events as function of energy and angle of incidence; 2) Measure charge spread (crosstalk) to adjacent pixels; 3) Assess transient recovery time.

  11. Hemopexin induces neuroprotection in the rat subjected to focal cerebral ischemia.

    Science.gov (United States)

    Dong, Beibei; Cai, Min; Fang, Zongping; Wei, Haidong; Zhu, Fangyun; Li, Guochao; Dong, Hailong; Xiong, Lize

    2013-06-10

    The plasma protein hemopexin (HPX) exhibits the highest binding affinity to free heme. In vitro experiments and gene-knock out technique have suggested that HPX may have a neuroprotective effect. However, the expression of HPX in the brain was not well elucidated and its expression after cerebral ischemia-reperfusion injury was also poorly studied. Furthermore, no in vivo data were available on the effect of HPX given centrally on the prognosis of focal cerebral ischemia. In the present study, we systematically investigated expression of HPX in normal rat brain by immunofluorescent staining. The results showed that HPX was mainly expressed in vascular system and neurons, as well as in a small portion of astrocytes adjacent to the vessels in normal rat brain. Further, we determined the role of HPX in the process of focal cerebral ischemic injury and explored the effects of HPX treatment in a rat model of transient focal cerebral ischemia. After 2 h' middle cerebral artery occlusion (MCAO) followed by 24 h' reperfusion, the expression of HPX was increased in the neurons and astrocytes in the penumbra area, as demonstrated by immunohistochemistry and Western blot techniques. Intracerebroventricular injection of HPX at the onset of reperfusion dose-dependently reduced the infarct volumes and improved measurements of neurological function of the rat subjected to transient focal cerebral ischemia. The neuroprotective effects of HPX sustained for up to 7 days after experiments. Our study provides a new insight into the potential neuroprotective role of HPX as a contributing factor of endogenous protective mechanisms against focal cerebral ischemia injury, and HPX might be developed as a potential agent for treatment of ischemic stroke.

  12. Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer

    Science.gov (United States)

    Charité, Jeroen; McFadden, David G.; Merlo, Giorgio; Levi, Giovanni; Clouthier, David E.; Yanagisawa, Masashi; Richardson, James A.; Olson, Eric N.

    2001-01-01

    Neural crest cells play a key role in craniofacial development. The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the branchial arch neural crest. The basic helix–loop–helix transcription factor dHAND is also required for craniofacial development, and in endothelin-1 (ET-1) mutant embryos, dHAND expression in the branchial arches is down-regulated, implicating it as a transcriptional effector of ET-1 action. To determine the mechanism that links ET-1 signaling to dHAND transcription, we analyzed the dHAND gene for cis-regulatory elements that control transcription in the branchial arches. We describe an evolutionarily conserved dHAND enhancer that requires ET-1 signaling for activity. This enhancer contains four homeodomain binding sites that are required for branchial arch expression. By comparing protein binding to these sites in branchial arch extracts from endothelin receptor A (EdnrA) mutant and wild-type mouse embryos, we identified Dlx6, a member of the Distal-less family of homeodomain proteins, as an ET-1-dependent binding factor. Consistent with this conclusion, Dlx6 was down-regulated in branchial arches from EdnrA mutant mice. These results suggest that Dlx6 acts as an intermediary between ET-1 signaling and dHAND transcription during craniofacial morphogenesis. PMID:11711438

  13. Hydrostatic pressure and shear stress affect endothelin-1 and nitric oxide release by endothelial cells in bioreactors.

    Science.gov (United States)

    Vozzi, Federico; Bianchi, Francesca; Ahluwalia, Arti; Domenici, Claudio

    2014-01-01

    Abundant experimental evidence demonstrates that endothelial cells are sensitive to flow; however, the effect of fluid pressure or pressure gradients that are used to drive viscous flow is not well understood. There are two principal physical forces exerted on the blood vessel wall by the passage of intra-luminal blood: pressure and shear. To analyze the effects of pressure and shear independently, these two stresses were applied to cultured cells in two different types of bioreactors: a pressure-controlled bioreactor and a laminar flow bioreactor, in which controlled levels of pressure or shear stress, respectively, can be generated. Using these bioreactor systems, endothelin-1 (ET-1) and nitric oxide (NO) release from human umbilical vein endothelial cells were measured under various shear stress and pressure conditions. Compared to the controls, a decrease of ET-1 production by the cells cultured in both bioreactors was observed, whereas NO synthesis was up-regulated in cells under shear stress, but was not modulated by hydrostatic pressure. These results show that the two hemodynamic forces acting on blood vessels affect endothelial cell function in different ways, and that both should be considered when planning in vitro experiments in the presence of flow. Understanding the individual and synergic effects of the two forces could provide important insights into physiological and pathological processes involved in vascular remodeling and adaptation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. The effect of serum magnesium levels and serum endothelin-1 levels on bone mineral density in protein energy malnutrition.

    Science.gov (United States)

    Ozturk, C F; Karakelleoglu, C; Orbak, Z; Yildiz, L

    2012-06-01

    An inadequate and imbalanced intake of protein and energy results in protein-energy malnutrition (PEM). It is known that bone mineral density and serum magnesium levels are low in malnourished children. However, the roles of serum magnesium and endothelin-1 (ET-1) levels in the pathophysiology of bone mineralization are obscure. Thus, the relationships between serum magnesium and ET-1 levels and the changes in bone mineral density were investigated in this study. There was a total of 32 subjects, 25 of them had PEM and seven were controls. While mean serum ET-1 levels of the children with kwashiorkor and marasmus showed no statistically significant difference, mean serum ET-1 levels of both groups were significantly higher than that of the control group. Serum magnesium levels were lower than normal value in 9 (36%) of 25 malnourished children. Malnourished children included in this study were divided into two subgroups according to their serum magnesium levels. While mean serum ET-1 levels in the group with low magnesium levels were significantly higher than that of the group with normal magnesium levels (p malnutrition. Our study suggested that lower magnesium levels and higher ET-1 levels might be important factors in changes of bone mineral density in malnutrition. We recommend that the malnourished patients, especially with hypomagnesaemia, should be treated with magnesium early.

  15. Endothelial dysfunction in high fructose containing diet fed rats: Increased nitric oxide and decreased endothelin-1 levels in liver tissue

    Directory of Open Access Journals (Sweden)

    Zeki Arı

    2010-09-01

    Full Text Available Objectives: Dietary high fructose consumption which is closely associated with endothelial dysfunction via insulin re-sistance has recently increased in developed countries. Insulin resistance has a promoter effect on many metabolic disorders such as syndrome X, polycystic ovary syndrome, Type 2 diabetes mellitus etc. Our aim in this study is to understand the impact of increased fructose intake on metabolisms of glucose, insulin and endothelial dysfunction by measuring nitric oxide (NO and endothelin-1 (ET-1 levels in hepatic tissue which is crucial in fructose metabolism.Materials and Methods: We designed an animal study to understand increased fructose intake on hepatic endothe-lium. Twenty adult male albino rats were divided into two groups; the study group (group 1, n=10 received isocaloric fructose enriched diet (fructose-fed rats, containing 18.3% protein, 60.3% fructose and 5.2% fat while the control group received purified regular chow (group 2, n=10 for 2 weeks. After feeding period, blood and hepatic tissue samples were collected and glucose, insulin, NO and ET-1 levels were analysed.Results: We found increased fasting glucose and insulin levels and impaired glucose tolerance in fructose fed rats. Higher NO and lower ET–1 levels were also detected in hepatic tissue samples of the group 1.Conclusion: Increased fructose consumption has deleterious effects on glucose tolerance, insulin resistance and may cause to endothelial dysfunction.

  16. Over, and Underexpression of Endothelin 1 and TGF-Beta Family Ligands and Receptors in Lung Tissue of Broilers with Pulmonary Hypertension

    Science.gov (United States)

    Dominguez-Avila, Norma; Ruiz-Castañeda, Gabriel; González-Ramírez, Javier; Fernandez-Jaramillo, Nora; Escoto, Jorge; Sánchez-Muñoz, Fausto; Marquez-Velasco, Ricardo; Bojalil, Rafael; Espinosa-Cervantes, Román; Sánchez, Fausto

    2013-01-01

    Transforming growth factor beta (TGFβ) is a family of genes that play a key role in mediating tissue remodeling in various forms of acute and chronic lung disease. In order to assess their role on pulmonary hypertension in broilers, we determined mRNA expression of genes of the TGFβ family and endothelin 1 in lung samples from 4-week-old chickens raised either under normal or cold temperature conditions. Both in control and cold-treated groups of broilers, endothelin 1 mRNA expression levels in lungs from ascitic chickens were higher than levels from healthy birds (P 0.05). BAMBI mRNA gene expression was lowest in birds with ascites only in the control group as compared with the values from healthy birds (P < 0.05). PMID:24286074

  17. Hemopexin induces neuroprotection in the rat subjected to focal cerebral ischemia

    OpenAIRE

    Dong, Beibei; Cai, Min; Fang, Zongping; Wei, Haidong; Zhu, Fangyun; Li, Guochao; Dong, Hailong; Xiong, Lize

    2013-01-01

    Background The plasma protein hemopexin (HPX) exhibits the highest binding affinity to free heme. In vitro experiments and gene-knock out technique have suggested that HPX may have a neuroprotective effect. However, the expression of HPX in the brain was not well elucidated and its expression after cerebral ischemia-reperfusion injury was also poorly studied. Furthermore, no in vivo data were available on the effect of HPX given centrally on the prognosis of focal cerebral ischemia. Results I...

  18. Intrahippocampal injection of endothelin-1 in immature rats results in neuronal death, development of epilepsy and behavioral abnormalities later in life

    Czech Academy of Sciences Publication Activity Database

    Máttéffyová, Adéla; Otáhal, Jakub; Tsenov, Grygoriy; Mareš, Pavel; Kubová, Hana

    2006-01-01

    Roč. 24, č. 2 (2006), s. 351-360 ISSN 0953-816X R&D Projects: GA ČR(CZ) GA305/06/0713; GA ČR(CZ) GD305/03/H148; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : endothelin-1 * epilepsy * immature rats Subject RIV: ED - Physiology Impact factor: 3.709, year: 2006

  19. Increasing plasma fibrinogen, but unchanged levels of intraplatelet cyclic nucleotides, plasma endothelin-1, factor VII, and neopterin during cholesterol lowering with fluvastatin.

    Science.gov (United States)

    Gottsäter, A; Anwaar, I; Lind, P; Mattiasson, I; Lindgärde, F

    1999-04-01

    Lipid-lowering statin treatment reduces cardiovascular morbidity and mortality and improves endothelial function in patients with hypercholesterolemia. The aim of the present study was to evaluate plasma levels of fibrinogen, factor VII, and the macrophage-derived inflammatory mediator neopterin during lipid lowering. In addition, the endothelial production of platelet antiaggregatory and vasodilatory factors such as nitric oxide and prostacyclin, and vasoconstrictive factors such as endothelin-1, was assessed. Plasma fibrinogen, factor VII, endothelin-1, and the neopterin and intraplatelet nitric oxide and prostacyclin mediators cyclic 3'-5'guanosine monophosphate (cGMP) and cyclic 3'-5'adenosine monophosphate (cAMP) were measured before and 6 months after the institution of treatment with fluvastatin in 17 patients (eight men and nine women, median age 60 years) with vascular disease and previously untreated hypercholesterolemia. After 6 months, a decrease of 1.62 mmol/l [1.26-2.18 (19%); P factor VII [from 1.14 IE/ml (0.58-1.38) to 1.22 IE/ml (0.96-1.46); NS], or plasma neopterin [from 8.6 nmol/l (7.1-11.5) to 8.7 nmol/l (7.9-11.3); NS]. In conclusion, during cholesterol-lowering treatment with fluvastatin, plasma levels of fibrinogen increased whereas intraplatelet cyclic nucleotide levels and plasma endothelin-1, factor VII and neopterin levels were unchanged.

  20. Influence of radiographic contrast media (Iodixanol and Iomeprol) on the endothelin-1 release from human arterial and venous endothelial cells cultured on an extracellular matrix.

    Science.gov (United States)

    Franke, R P; Fuhrmann, R; Hiebl, B; Jung, F

    2012-01-01

    Various radiographic contrast media (RCM) are available for visualization of blood vessels in interventional cardiology which can vary widely in their physicochemical properties thereby influencing different functions of blood cells. In the in vitro study described here the influence of two RCMs on arterial as well as on venous endothelial cells was compared to control cultures and examined under statical culture conditions, thus eliminating the influence of RCM viscosity almost completely. The supplementation of the culture medium with RCM (30% v/v) resulted in clearly different reactions of the endothelial cells exposed. Exposition to Iodixanol supplemented culture medium was followed by endothelin-1 release from venous endothelial cells which was equivalent to the endothelin-1 release from venous control cultures. Compared to control cultures, venous endothelial cells exposed to culture medium supplemented with Iomeprol displayed a completely different reaction, the increase in endothelin-1 secretion was missing completely after a 12 hours exposure. Following a 12 hours exposure to both RCMs there were no longer endothelial cells adherent, neither in venous nor in arterial endothelial cell cultures. The study showed that not the wall shear stress was responsible for the differing effects visible after 1.5 min, 5 min, and 12 hours exposure to culture media supplemented with RCM but differences in chemotoxicity of the RCM applied.

  1. Knockout of endothelial cell-derived endothelin-1 attenuates skin fibrosis but accelerates cutaneous wound healing.

    Directory of Open Access Journals (Sweden)

    Katsunari Makino

    Full Text Available Endothelin (ET-1 is known for the most potent vasoconstrictive peptide that is released mainly from endothelial cells. Several studies have reported ET-1 signaling is involved in the process of wound healing or fibrosis as well as vasodilation. However, little is known about the role of ET-1 in these processes. To clarify its mechanism, we compared skin fibrogenesis and wound repair between vascular endothelial cell-specific ET-1 knockout mice and their wild-type littermates. Bleomycin-injected fibrotic skin of the knockout mice showed significantly decreased skin thickness and collagen content compared to that of wild-type mice, indicating that bleomycin-induced skin fibrosis is attenuated in the knockout mice. The mRNA levels of transforming growth factor (TGF-β were decreased in the bleomycin-treated skin of ET-1 knockout mice. On the other hand, skin wound healing was accelerated in ET-1 knockout mice, which was indicated by earlier granulation tissue reduction and re-epithelialization in these mice. The mRNA levels of TGF-β, tumor necrosis factor (TNF-α and connective tissue growth factor (CTGF were reduced in the wound of ET-1 knockout mice. In endothelial ET-1 knockout mouse, the expression of TNF-α, CTGF and TGF-β was down-regulated. Bosentan, an antagonist of dual ET receptors, is known to attenuate skin fibrosis and accelerate wound healing in systemic sclerosis, and such contradictory effect may be mediated by above molecules. The endothelial cell-derived ET-1 is the potent therapeutic target in fibrosis or wound healing, and investigations of the overall regulatory mechanisms of these pathological conditions by ET-1 may lead to a new therapeutic approach.

  2. Preservation of endothelium-dependent relaxation in atherosclerotic mice with endothelium-restricted endothelin-1 overexpression.

    Science.gov (United States)

    Mian, Muhammad Oneeb Rehman; Idris-Khodja, Noureddine; Li, Melissa W; Leibowitz, Avshalom; Paradis, Pierre; Rautureau, Yohann; Schiffrin, Ernesto L

    2013-10-01

    In human atherosclerosis, which is associated with elevated plasma and coronary endothelin (ET)-1 levels, ETA receptor antagonists improve coronary endothelial function. Mice overexpressing ET-1 specifically in the endothelium (eET-1) crossed with atherosclerosis-prone apolipoprotein E knockout mice (Apoe(-/-)) exhibit exaggerated high-fat diet (HFD)-induced atherosclerosis. Since endothelial dysfunction often precedes atherosclerosis development, we hypothesized that mice overexpressing endothelial ET-1 on a genetic background deficient in apolipoprotein E (eET-1/Apoe(-/-)) would have severe endothelial dysfunction. To test this hypothesis, we investigated endothelium-dependent relaxation (EDR) to acetylcholine in eET-1/Apoe(-/-) mice. EDR in mesenteric resistance arteries from 8- and 16-week-old mice fed a normal diet or HFD was improved in eET-1/Apoe(-/-) compared with Apoe(-/-) mice. Nitric oxide synthase (NOS) inhibition abolished EDR in Apoe(-/-). EDR in eET-1/Apoe(-/-) mice was resistant to NOS inhibition irrespective of age or diet. Inhibition of cyclooxygenase, the cytochrome P450 pathway, and endothelium-dependent hyperpolarization (EDH) resulted in little or no inhibition of EDR in eET-1/Apoe(-/-) compared with wild-type (WT) mice. In eET-1/Apoe(-/-) mice, blocking of EDH or soluble guanylate cyclase (sGC), in addition to NOS inhibition, decreased EDR by 36 and 30%, respectively. The activation of 4-aminopyridine-sensitive voltage-dependent potassium channels (Kv) during EDR was increased in eET-1/Apoe(-/-) compared with WT mice. We conclude that increasing eET-1 in mice that develop atherosclerosis results in decreased mutual dependence of endothelial signaling pathways responsible for EDR, and that NOS-independent activation of sGC and increased activation of Kv are responsible for enhanced EDR in this model of atherosclerosis associated with elevated endothelial and circulating ET-1.

  3. Analysis of endotoxin and endothelin-1 levels in patients with type 1 hepatorenal syndrome

    Directory of Open Access Journals (Sweden)

    GAO Baoxiu

    2014-01-01

    Full Text Available ObjectiveTo analyze the clinical data, laboratory parameters, infection rate, and serum procalcitonin (PCT and ET-1 levels of patients with cirrhotic ascites and type 1 hepatorenal syndrome (HRS and to investigate the roles of endotoxin and ET-1 in the development of HRS. MethodsBetween January 2009 and October 2012, 56 inpatients with cirrhotic ascites and type 1 HRS (HRS group and 60 inpatients with cirrhotic ascites who had normal renal function (non-HRS group were included in the study. Their general data, causes of liver cirrhosis, infection rates and types, Child-Pugh classification, systemic inflammatory response syndrome (SIRS score, and mean arterial pressure (MAP were recorded; blood samples were collected to evaluate liver and renal function and measure serum electrolyte, PCT, and ET-1 levels. The clinical data and laboratory parameters were compared between the two groups. Categorical data were analyzed by chi-square test; comparison of normally distributed continuous data between the two groups was made by independent-samples t test, and comparison of non-normally distributed continuous data between the two groups was made by Wilcoxon rank sum test. ResultsThe infection rate of HRS group (75.0% was significantly higher than that of non-HRS group (28.4% (χ2=11.91, P<0.05. The PCT and ET-1 levels and SIRS score of HRS group [8.72 (3.14, 31.68 ng/L, 13.04±2.82 pg/ml, and 2.1±1.1] were significantly higher than those of non-HRS group [0.11 (0.04, 0.45 ng/L, 5.76±1.68 pg/ml, and 0.6±0.6] (P<0.05. In addition, the HRS group had significantly higher serum urea, creatine, cystatin C, and K levels than the non-HRS group (P<0.05, while the HRS group had significantly lower Na and Cl levels than the non-HRS group (P<0.05. There were no significant differences in ALT and AST levels between the two groups (P>005. ConclusionEndotoxin causes elevated expression of ET-1, and ET-1 induces renal perfusion deficiency by

  4. Big endothelin-1 and nitric oxide in hypertensive elderly patients with and without obstructive sleep apnea-hypopnea syndrome.

    Science.gov (United States)

    Anunciato, Iara Felicio; Lobo, Rômulo Rebouças; Coelho, Eduardo Barbosa; Verri, Waldiceu Aparecido; Eckeli, Alan Luiz; Evora, Paulo Roberto Barbosa; Nobre, Fernando; Moriguti, Júlio César; Ferriolli, Eduardo; Lima, Nereida Kilza da Costa

    2013-10-01

    The role of oxidative stress in hypertensive elderly patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) is unknown. The purpose was to evaluate the levels of big endothelin-1 (Big ET-1) and nitric oxide (NO) in elderly hypertensive patients with and without moderate to severe OSAHS. Volunteers were hospitalized for 24 h. We obtained the following data: body mass index (BMI); 24-ambulatory blood pressure monitoring; and current medication. Arterial blood was collected at 7 pm and 7 am for determining plasma NO and Big ET-1 levels. Pulse oximetry was performed during sleep. Pearson's or Spearman's correlation and univariate analysis of variance were used for statistical analysis. We studied 25 subjects with OSAHS (group 1) and 12 without OSAHS (group 2) aged 67.0 ± 6.5 years and 67.8 ± 6.8 years, respectively. No significant differences were observed between the groups in BMI; number of hours of sleep; 24-h systolic and diastolic BPs; awake BP, sleep BP and medications to control BP between groups. No differences were detected in plasma Big ET-1 and NO levels at 19:00 h, but plasma Big ET-1 levels at 7:00 h were higher in group 1 (p =0.03). In group 1, a negative correlation was also observed between the mean arterial oxyhemoglobin saturation level, 24-h systolic BP (p = 0.03, r = -0.44), and Big ET-1 (p = 0.04, r = -0.41). On comparing elderly hypertensive patients with and without OSAHS having similar BP and BMI, we observed higher Big ET-1 levels After sleep in the OSAHS group. NO levels did not differ between the hypertensive patients with or without OSAHS.

  5. Co-inhibition of Angiotensin II Receptor and Endothelin-1 Attenuates Renal Injury in Unilateral Ureteral Obstructed Mice

    Directory of Open Access Journals (Sweden)

    Yoon-Kyung Chang

    2016-07-01

    Full Text Available Background/Aims: Both endothelin-1 (ET-1 and the renin-angiotensin system (RAS may play important roles in renal fibrosis in the obstructed kidney. However, there have been few clear demonstrations of a relationship between their activation and additive or synergistic roles in renal fibrosis. We investigated the protective roles and relationship between renal RAS and ET-1 in unilateral ureteral obstruction (UUO mice. Methods: 8-week-old male C57BL/6 mice were divided into seven groups: sham, bosentan+sham, valsartan+sham, vehicle+UUO, bosentan+UUO, valsartan+UUO, and valsartan+bosentan+UUO. Valsartan and bosentan were administered orally using an NG tube (valsartan 10 mg/kg/day, bosentan 100 mg/kg/day for 8 days, after which the molecular and structural kidney parameters were evaluated. Bosentan treatment elevated plasma renin activity, renal renin, and AT1R expression in UUO mice. Results: Although valsartan decreased plasma ET-1 in these mice, it did not affect ET(A or ET(B in their kidneys. Co-treatment with valsartan and bosentan decreased ET-1 in these mice compared to the single treatments. Bosentan, but not valsartan, elevated eNOS expression in their kidneys. Co-treatment with valsartan and bosentan reduced TGF-β, α-SMA, and collagen IV expression, and the Masson's trichrome stained area in their kidneys. Conclusions: Bosentan and valsartan acted complementarily, and co-treatment with both drugs had an additive protective effect against renal fibrosis.

  6. Prognostic value of plasma midregional pro-adrenomedullin and C-terminal-pro-endothelin-1 in chronic heart failure outpatients.

    Science.gov (United States)

    Adlbrecht, Christopher; Hülsmann, Martin; Strunk, Guido; Berger, Rudolf; Mörtl, Deddo; Struck, Joachim; Morgenthaler, Nils G; Bergmann, Andreas; Jakowitsch, Johannes; Maurer, Gerald; Lang, Irene M; Pacher, Richard

    2009-04-01

    The identification of chronic heart failure (CHF) patients at high risk of adverse outcome remains a challenge. New peptides are emerging that may give additional information. In CHF patients, endothelin (ET) levels predict mortality risk. Adrenomedullin has been shown to predict mortality in ischaemic heart failure, but not in unselected or non-ischaemic CHF patients. Moreover, ADM and ET have never been assessed in one model. The aim of the present study was to assess the prognostic value of midregional-pro-adrenomedullin (MR-proADM) and C-terminal-pro-endothelin-1 (CT-proET-1) in outpatients with CHF. We measured plasma MR-proADM and CT-proET-1 levels in 786 consecutive CHF outpatients and compared them with B-type natriuretic peptide (BNP) levels. At 24-month follow-up, 233 patients had died. A stepwise forward Cox regression model with age, sex, estimated glomerular filtration rate, NYHA > II, left ventricular ejection fraction (LVEF), MR-proADM, CT-proET-1, and BNP as possible predictors revealed that MR-proADM levels [hazard ratio (HR) = 1.77, P II (HR = 1.86, P < 0.001) were predictors of death at 24 months. When the analysis was repeated dependent on NYHA-stage, MR-proADM (HR = 2.12, P < 0.001) and LVEF (HR = 0.96, P = 0.006) were significant markers, but only in patients with mild/moderate CHF. Our data suggest that MR-proADM may be an important prognostic humoral marker, especially in mild/moderately symptomatic and non-ischaemic CHF patients.

  7. Orphan nuclear receptor Nur77 is a novel negative regulator of endothelin-1 expression in vascular endothelial cells.

    Science.gov (United States)

    Qin, Qing; Chen, Ming; Yi, Bing; You, Xiaohua; Yang, Ping; Sun, Jianxin

    2014-12-01

    Endothelin-1 (ET-1) produced by vascular endothelial cells plays essential roles in the regulation of vascular tone and development of cardiovascular diseases. The objective of this study is to identify novel regulators implicated in the regulation of ET-1 expression in vascular endothelial cells (ECs). By using quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), we show that either ectopic expression of orphan nuclear receptor Nur77 or pharmacological activation of Nur77 by 6-mercaptopurine (6-MP) substantially inhibits ET-1 expression in human umbilical vein endothelial cells (HUVECs), under both basal and thrombin-stimulated conditions. Furthermore, thrombin-stimulated ET expression is significantly augmented in both Nur77 knockdown ECs and aort from Nur77 knockout mice, suggesting that Nur77 is a negative regulator of ET-1 expression. Inhibition of ET-1 expression by Nur77 occurs at gene transcriptional levels, since Nur77 potently inhibits ET-1 promoter activity, without affecting ET-1 mRNA stability. As shown in electrophoretic mobility shift assay (EMSA), Nur77 overexpression markedly inhibits both basal and thrombin-stimulated transcriptional activity of AP-1. Mechanistically, we demonstrate that Nur77 specially interacts with c-Jun and inhibits AP-1 dependent c-Jun promoter activity, which leads to a decreased expression of c-Jun, a critical component involved in both AP-1 transcriptional activity and ET-1 expression in ECs. These findings demonstrate that Nur77 is a novel negative regulator of ET-1 expression in vascular ECs through an inhibitory interaction with the c-Jun/AP-1 pathway. Activation of Nur77 may represent a useful therapeutic strategy for preventing certain cardiovascular diseases, such as atherosclerosis and pulmonary artery hypertension. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Correlation of endothelin-1 concentration and angiotensin-converting enzyme activity with the staging of liver fibrosis.

    Science.gov (United States)

    Kardum, Dusko; Fabijanić, Damir; Lukić, Anita; Romić, Zeljko; Petrovecki, Mladen; Bogdanović, Zoran; Jurić, Klara; Urek-Crncević, Marija; Banić, Marko

    2012-06-01

    Increased serum angiotensin-converting enzyme (SACE) activity and serum concentration of endothelin-1 (ET-1) were found in liver cirrhosis. We investigated a correlation between the different stages of liver fibrosis and SACE activity and serum ET-1 concentration. Seventy patients with pathohistologically established chronic liver disease were divided in three groups according to Ishak criteria for liver fibrosis: minimal fibrosis (Ishak score 0-1, n =20), medium fibrosis (Ishak score 2-5, n=20) and cirrhosis (Ishak score 6, n=30). SACE activity and ET-1 concentration were determined using commercial ELISA kits. SACE activity and ET-1 concentrations were proportional to the severity of disease, the highest being in patients with liver cirrhosis. Maximal increase in SACE activity was found between minimal and medium fibrosis while maximal increase in ET-1 concentration was revealed between medium fibrosis and cirrhosis. The analysis of the Receiver Operating Characteristic (ROC) curve for SACE activity suggested a cut-off value to separate minimal from medium fibrosis at 59.00 U/L (sensitivity 100%, specificity 64.7%). The cut-off value for serum ET-1 concentration to separate medium fibrosis from cirrhosis was 12.4 pg/mL (sensitivity 96.8%, specificity 94.4%). A positive correlation between SACE activity and ET-1 concentration was registered (Spearman's ñ = 0.438, p = 0.004). Both SACE activity and ET-1 concentration were increased in all stages of liver fibrosis. Cut-off points for SACE activity and ET-1 concentration could be a biochemical marker for the progression of fibrosis. Positive correlation between SACE activity and ET-1 concentration might indicate their interaction in the development of liver cirrhosis.

  9. Radiation-induced focal cortical necrosis of the femur presenting as a lytic lesion

    Energy Technology Data Exchange (ETDEWEB)

    Ilaslan, Hakan; Schils, Jean [Cleveland Clinic, Musculoskeletal Radiology, Cleveland, OH (United States); Joyce, Michael [Cleveland Clinic, Orthopedic Oncology, Cleveland, OH (United States); Shah, Chirag [Cleveland Clinic, Radiation Oncology, Cleveland, OH (United States); Zhang, Yaxia [Cleveland Clinic, Pathology, Cleveland, OH (United States)

    2017-11-15

    Management of soft tissue sarcomas is often complicated, requiring radiation before and in some cases after limb-sparing surgery. Radiation necrosis is a severe complication after radiation treatment and is typically dose related and involves medullary bone. We report on two cases of hitherto unreported focal circumscribed intra-cortical lytic lesions within the radiation portal, which appeared 19 months and 31 months, respectively, after the conclusion of radiation treatment. Both patients had a history of soft tissue sarcoma treated with radiation (66 Gy) and surgical resection. Biopsy of these lesions showed necrotic bone attributed to radiation. (orig.)

  10. Influence of the distance between target surface and focal point on the expansion dynamics of a laser-induced silicon plasma with spatial confinement

    Science.gov (United States)

    Zhang, Dan; Chen, Anmin; Wang, Xiaowei; Wang, Ying; Sui, Laizhi; Ke, Da; Li, Suyu; Jiang, Yuanfei; Jin, Mingxing

    2018-05-01

    Expansion dynamics of a laser-induced plasma plume, with spatial confinement, for various distances between the target surface and focal point were studied by the fast photography technique. A silicon wafer was ablated to induce the plasma with a Nd:YAG laser in an atmospheric environment. The expansion dynamics of the plasma plume depended on the distance between the target surface and focal point. In addition, spatially confined time-resolved images showed the different structures of the plasma plumes at different distances between the target surface and focal point. By analyzing the plume images, the optimal distance for emission enhancement was found to be approximately 6 mm away from the geometrical focus using a 10 cm focal length lens. This optimized distance resulted in the strongest compression ratio of the plasma plume by the reflected shock wave. Furthermore, the duration of the interaction between the reflected shock wave and the plasma plume was also prolonged.

  11. 8C.03: A KEY ROLE FOR ENDOTHELIN-1 IN THE PATHOGENESIS OF PREECLAMPSIA AND THE ASSOCIATED SUPPRESSION OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM.

    Science.gov (United States)

    Verdonk, K; Saleh, L; Smilde, J E; van Ingen, M M; Garrelds, I M; Friesema, E C; Russcher, H; Steegers, E A P; van den Meiracker, A H; Visser, W; Danser, A H J

    2015-06-01

    Women with preeclampsia (PE) display low renin-angiotensin-aldosterone system (RAAS) activity and a high anti-angiogenic state, the latter characterized by high levels of soluble Fms-like tyrosine kinase-1(sFlt-1) and reduced levels of placental growth factor (PlGF). In the present study, we hypothesized that the RAAS suppression in PE is the consequence of the disturbed angiogenic balance. In a group of pregnant women with hypertensive disease of pregnancy and a group of healthy pregnant women, matched for gestational age (GA) we measured mean arterial blood pressure (MAP), urinary protein-to-creatinine ratio (PCR), and the plasma levels of sFlt-1, PlGF, albumin, creatinine, endothelin-1 (ET-1), renin (concentration and activity, PRC and PRA), angiotensinogen, and aldosterone. Since initial analysis revealed that these parameters strongly correlated with each other, multiple regression analysis was applied to establish independent determinants of ET-1, PRC, aldosterone and PCR. A sFlt-1/PlGF ratio >85 was considered to be representative for a high anti-angiogenic state. Of the 103 pregnant women included, 65 had a sFlt-1/PlGF ratio 85. Plasma ET-1 and creatinine levels were increased in women with a high ratio, whereas PRA and the plasma levels of renin, angiotensinogen, aldosterone and albumin were decreased in these women. The PRA-aldosterone relationship was identical in both groups. Multiple regression analysis revealed that PRC correlated independently with MAP and plasma ET-1 (R2 0.30). In turn, plasma ET-1 correlated positively with sFlt-1 and negatively with PRC (R2 0.52). Independent determinants of plasma aldosterone were GA and PRA (R2 0.56). Finally we found that plasma PlGF, plasma ET-1 and MAP determined PCR (R2 0.69). The high anti-angiogenic state in PE induces ET-1 activation. Together with the increased MAP in PE this factor suppresses renin release, and in parallel (via PRA reduction) aldosterone synthesis. The identical reduction in PRA and

  12. Focal myositis

    International Nuclear Information System (INIS)

    Kransdorf, M.J.; Temple, H.T.; Sweet, D.E.

    1998-01-01

    Focal myositis is a pseudotumor of soft tissue that typically occurs in the deep soft tissue of the extremities, and is a relatively rare lesion. There is a wide clinical spectrum, with approximately one-third of patients with focal myositis subsequently developing polymyositis, and clinical symptoms of generalized weakness, fever, myalgia, and weight loss, with elevation of creatine phosphokinase. We report the case of a patient with focal myositis who subsequently developed myositis ossificans-like features. (orig.)

  13. Inhibiting focal adhesion kinase (FAK) blocks IL-4 induced VCAM-1 expression and eosinophil recruitment in vitro and in vivo.

    Science.gov (United States)

    Aulakh, Gurpreet K; Petri, Björn; Wojcik, Katarzyna M; Colarusso, Pina; Lee, James J; Patel, Kamala D

    2018-04-06

    Leukocyte recruitment plays a critical role during both normal inflammation and chronic inflammatory diseases, and ongoing studies endeavor to better understand the complexities of this process. Focal adhesion kinase (FAK) is well known for its role in cancer, yet it also has been shown to regulate aspects of neutrophil and B16 melanoma cell recruitment by rapidly influencing endothelial cell focal adhesion dynamics and junctional opening. Recently, we found that FAK related non-kinase (FRNK), a protein that is often used as a FAK dominant negative, blocked eosinophil transmigration by preventing the transcription of vascular cell adhesion molecule-1 (VCAM-1) and eotaxin-3 (CCL26). Surprisingly, the blocking occurred even in the absence of endogenous FAK. To better understand the role of FAK in leukocyte recruitment, we used a FAK-specific inhibitor (PF-573228) and determined the effect on IL-4 induced eosinophil recruitment in vitro and in vivo. PF-573228 prevented the expression of VCAM-1 and CCL26 expression in IL-4-stimulated human endothelial cells in vitro. As a result, eosinophil adhesion and transmigration were blocked. PF-572338 also prevented IL-4-induced VCAM-1 expression in vivo. Using brightfield intravital microscopy, we found that PF-573228 decreased leukocyte rolling flux, adhesion, and emigration. We specifically examined eosinophil recruitment in vivo by using an eosinophil-GFP reporter mouse and found PF-573228 attenuated eosinophil emigration. This study reveals that a FAK inhibitor influences inflammation through its action on eosinophil recruitment. ©2018 Society for Leukocyte Biology.

  14. Endothelin-1 and antiangiogenesis

    NARCIS (Netherlands)

    S. Lankhorst (Stephanie); A.H.J. Danser (Jan); A.H. van den Meiracker (Anton)

    2016-01-01

    textabstractAntiangiogenesis, targeting vascular endothelial growth factor (VEGF), has become a well-established treatment for patients with cancer. This treatment is associated with nitric oxide (NO) suppression and a dose-dependent activation of the endothelin system, resulting in

  15. Focal myositis

    International Nuclear Information System (INIS)

    Galloway, H.R.; Dahlstrom, J.E.; Bennett, G.M.

    2001-01-01

    Focal myositis is a rare, benign focal inflammation of muscle. The lesion often presents as a mass that may be mistaken for a soft tissue sarcoma. This report describes the MRI and histopathological features of a case and illustrates how the diagnosis may be suspected on the basis of the MR findings. Copyright (2001) Blackwell Science Pty Ltd

  16. Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia

    DEFF Research Database (Denmark)

    Inácio, Ana R; Liu, Yawei; Clausen, Bettina H

    2015-01-01

    of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-βKO mice, we found a higher percentage of total B cells but a similar percentage of mature and activated B cells, collectively indicating a higher proliferation rate. The additional differential regulation......BACKGROUND: Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death...... strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. RESULTS: Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a higher number...

  17. A zebrafish screen for craniofacial mutants identifies wdr68 as a highly conserved gene required for endothelin-1 expression

    Directory of Open Access Journals (Sweden)

    Amsterdam Adam

    2006-06-01

    Full Text Available Abstract Background Craniofacial birth defects result from defects in cranial neural crest (NC patterning and morphogenesis. The vertebrate craniofacial skeleton is derived from cranial NC cells and the patterning of these cells occurs within the pharyngeal arches. Substantial efforts have led to the identification of several genes required for craniofacial skeletal development such as the endothelin-1 (edn1 signaling pathway that is required for lower jaw formation. However, many essential genes required for craniofacial development remain to be identified. Results Through screening a collection of insertional zebrafish mutants containing approximately 25% of the genes essential for embryonic development, we present the identification of 15 essential genes that are required for craniofacial development. We identified 3 genes required for hyomandibular development. We also identified zebrafish models for Campomelic Dysplasia and Ehlers-Danlos syndrome. To further demonstrate the utility of this method, we include a characterization of the wdr68 gene. We show that wdr68 acts upstream of the edn1 pathway and is also required for formation of the upper jaw equivalent, the palatoquadrate. We also present evidence that the level of wdr68 activity required for edn1 pathway function differs between the 1st and 2nd arches. Wdr68 interacts with two minibrain-related kinases, Dyrk1a and Dyrk1b, required for embryonic growth and myotube differentiation, respectively. We show that a GFP-Wdr68 fusion protein localizes to the nucleus with Dyrk1a in contrast to an engineered loss of function mutation Wdr68-T284F that no longer accumulated in the cell nucleus and failed to rescue wdr68 mutant animals. Wdr68 homologs appear to exist in all eukaryotic genomes. Notably, we found that the Drosophila wdr68 homolog CG14614 could substitute for the vertebrate wdr68 gene even though insects lack the NC cell lineage. Conclusion This work represents a systematic

  18. Modulation by endothelin-1 of spontaneous activity and membrane currents of atrioventricular node myocytes from the rabbit heart.

    Directory of Open Access Journals (Sweden)

    Stéphanie C Choisy

    Full Text Available The atrioventricular node (AVN is a key component of the cardiac pacemaker-conduction system. Although it is known that receptors for the peptide hormone endothelin-1 (ET-1 are expressed in the AVN, there is very little information available on the modulatory effects of ET-1 on AVN electrophysiology. This study characterises for the first time acute modulatory effects of ET-1 on AVN cellular electrophysiology.Electrophysiological experiments were conducted in which recordings were made from rabbit isolated AVN cells at 35-37°C using the whole-cell patch clamp recording technique.Application of ET-1 (10 nM to spontaneously active AVN cells led rapidly (within ~13 s to membrane potential hyperpolarisation and cessation of spontaneous action potentials (APs. This effect was prevented by pre-application of the ET(A receptor inhibitor BQ-123 (1 µM and was not mimicked by the ET(B receptor agonist IRL-1620 (300 nM. In whole-cell voltage-clamp experiments, ET-1 partially inhibited L-type calcium current (I(Ca,L and rapid delayed rectifier K(+ current (I(Kr, whilst it transiently activated the hyperpolarisation-activated current (I(f at voltages negative to the pacemaking range, and activated an inwardly rectifying current that was inhibited by both tertiapin-Q (300 nM and Ba(2+ ions (2 mM; each of these effects was sensitive to ET(A receptor inhibition. In cells exposed to tertiapin-Q, ET-1 application did not produce membrane potential hyperpolarisation or immediate cessation of spontaneous activity; instead, there was a progressive decline in AP amplitude and depolarisation of maximum diastolic potential.Acutely applied ET-1 exerts a direct modulatory effect on AVN cell electrophysiology. The dominant effect of ET-1 in this study was activation of a tertiapin-Q sensitive inwardly rectifying K(+ current via ET(A receptors, which led rapidly to cell quiescence.

  19. Effects of a Single Dose of Erythropoietin on Motor Function and Cognition after Focal Brain Ischemia in Adult Rats

    Directory of Open Access Journals (Sweden)

    Michaela Hralová

    2014-01-01

    Full Text Available We tested the influence of erythropoietin (EPO, a basic cytokine in erythropoiesis regulation, on the process of motor function and cognition after focal brain ischemia induced by a local application of endothelin. Endothelin-1 (ET-1 induced short lasting strong vasoconstriction, with described impact on the structure and on the function of neuronal cells. Neurological description of motor function and Morris water maze test (the swimming test is one of most widely used methods for studying cognitive functions in rodents were used to study the process of learning and memory in three-month-old male albino Wistar rats (n=52. Both tests were performed one week before, and three weeks after ischemia induction (endothelin application on the cortex in the area of a. cerebri media dx.. Experimental group received i.p. injection of EPO (5,000 IU/kg body weight, 10 min before endothelin application. Control group of animals received one i.p. injection of saline at the dose of 1 ml/kg body weight at the same time. Only sham surgery was performed in the third group of animals. Rats with EPO pretreatment before the experimental lesion exhibited significantly better motor and cognitive function then those with saline injection. No significant changes in the motor and cognitive function were found in the third group of rats (sham operated controls.

  20. Focal myositis

    Energy Technology Data Exchange (ETDEWEB)

    Kransdorf, M.J. [Saint Mary`s Hospital, Richmond, VA (United States). Dept. of Radiol.]|[Department of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States); Temple, H.T. [Department of Orthopedic Surgery, University of Virginia Health Sciences Center, Charlottesville, Virginia (United States)]|[Department of Orthopedic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States); Sweet, D.E. [Department of Orthopedic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States)

    1998-05-01

    Focal myositis is a pseudotumor of soft tissue that typically occurs in the deep soft tissue of the extremities, and is a relatively rare lesion. There is a wide clinical spectrum, with approximately one-third of patients with focal myositis subsequently developing polymyositis, and clinical symptoms of generalized weakness, fever, myalgia, and weight loss, with elevation of creatine phosphokinase. We report the case of a patient with focal myositis who subsequently developed myositis ossificans-like features. (orig.) With 3 figs., 25 refs.

  1. Effect of carbamazepine (Tegretol) on seizure and EEG patterns in monkeys with alumina-induced focal motor and hippocampal foci.

    Science.gov (United States)

    David, J; Grewal, R S

    1976-12-01

    Qualitative and quantitative aspects of chronic carbamazepine (Tegretol) medication on focal seizures and associated interictal EEG abnormalities in Rhesus monkeys with alumina-induced foci in either the sensorimotor cortex or the hipocampus was investigated. In both groups of animals, carbamazepine produced qualitative control of visible seizures and reduced intracortical spike propagation, but did not cause complete normalization of the background EEG; quantitative indices, such as spike density and amount of paroxysmal discharge representative of abnormal EEG activity, were significantly reduced with respect to predrug values during medication and after cessation as well. Threshold to pentylenetetrazol was elevated by carbamazepine in both groups of epileptic monkeys. Aggressivity and other clinical manifestations in monekys with hippocampal foci were markedly reduced by carbamazepine.

  2. Cerebroprotective Effect of Moringa oleifera against Focal Ischemic Stroke Induced by Middle Cerebral Artery Occlusion

    Directory of Open Access Journals (Sweden)

    Woranan Kirisattayakul

    2013-01-01

    Full Text Available The protection against ischemic stroke is still required due to the limitation of therapeutic efficacy. Based on the role of oxidative stress in stroke pathophysiology, we determined whether Moringa oleifera, a plant possessing potent antioxidant activity, protected against brain damage and oxidative stress in animal model of focal stroke. M. oleifera leaves extract at doses of 100, 200 and 400 mg·kg−1 was orally given to male Wistar rats (300–350 g once daily at a period of 2 weeks before the occlusion of right middle cerebral artery (Rt.MCAO and 3 weeks after Rt.MCAO. The determinations of neurological score and temperature sensation were performed every 7 days throughout the study period, while the determinations of brain infarction volume, MDA level, and the activities of SOD, CAT, and GSH-Px were performed 24 hr after Rt.MCAO. The results showed that all doses of extract decreased infarction volume in both cortex and subcortex. The protective effect of medium and low doses of extract in all areas occurred mainly via the decreased oxidative stress. The protective effect of the high dose extract in striatum and hippocampus occurred via the same mechanism, whereas other mechanisms might play a crucial role in cortex. The detailed mechanism required further exploration.

  3. Focal hot spot induced by a central subclavian line on bone scan.

    Science.gov (United States)

    Moslehi, Masood; Cheki, Mohsen; Dehghani, Tohid; Eftekhari, Mansoureh

    2014-01-01

    The diagnostic accuracy of nuclear medicine reporting can be improved by awareness of these instrument-related artifacts. Both awareness and experience are also important when it comes to detecting and identifying normal (and abnormal) variants. We present a case of hot spot on the upper right chest in the region of right subclavicular region resulting from injection of radiotracer from central subclavian line. A 52-year-old woman with a history of left breast cancer and recent bone pain was referred to our nuclear medicine department for skeletal survey. Anterior views of chest show a focus of increased radiotracer uptake corresponding to anterior arch of one of the right second rib. The nuclear physician reported it as a focal rib bony lesion and recommended radiological evaluation. As technician later explained, physicians realized that injection site was a central subclavian line on the right side and hot spot on that region is due to injection site. The appearance of both skeletal and soft-tissue uptake depends heavily on imaging technique (such as the route of radiotracer administration) and the interpreting physicians should be aware of the impact of technical factors on image quality.

  4. Effects of transcranial focal electrical stimulation via tripolar concentric ring electrodes on pentylenetetrazole-induced seizures in rats.

    Science.gov (United States)

    Besio, W G; Makeyev, O; Medvedev, A; Gale, K

    2013-07-01

    To study the effects of noninvasive transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCRE) on the electrographic and behavioral activity from pentylenetetrazole (PTZ)-induced seizures in rats. The TCREs were attached to the rat scalp. PTZ was administered and, after the first myoclonic jerk was observed, TFS was applied to the TFS treated group. The electroencephalogram (EEG) and behavioral activity were recorded and studied. In the case of the TFS treated group, after TFS, there was a significant (p=0.001) decrease in power compared to the control group in delta, theta, and alpha frequency bands. The number of myoclonic jerks was significantly different (p=0.002) with median of 22 and 4.5 for the control group and the TFS treated groups, respectively. The duration of myoclonic activity was also significantly different (p=0.031) with median of 17.56 min for the control group versus 8.63 min for the TFS treated group. At the same time there was no significant difference in seizure onset latency and maximal behavioral seizure activity score between control and TFS treated groups. TFS via TCREs interrupted PTZ-induced seizures and electrographic activity was reduced toward the "baseline." The significantly reduced electrographic power, number of myoclonic jerks, and duration of myoclonic activity of PTZ-induced seizures suggests that TFS may have an anticonvulsant effect. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Down-regulation of procaspase-8 expression by focal adhesion kinase protects HL-60 cells from TRAIL-induced apoptosis

    International Nuclear Information System (INIS)

    Tamagiku, Yuji; Sonoda, Yoshiko; Kunisawa, Mari; Ichikawa, Daiju; Murakami, Yayoi; Aizu-Yokota, Eriko; Kasahara, Tadashi

    2004-01-01

    We have demonstrated that focal adhesion kinase (FAK)-overexpressed (HL-60/FAK) cells have marked resistance against various apoptotic stimuli such as hydrogen peroxide, etoposide, and ionizing radiation compared with the vector-transfected (HL-60/Vect) cells. HL-60/FAK cells are highly resistant to TRAIL-induced apoptosis, while original HL-60 or HL-60/Vect cells were sensitive. TRAIL at 500 ng/ml induced significant DNA fragmentation, activation of caspase-8 and 3, the processing of a proapoptotic BID, and mitochondrial release of cytochrome c in HL-60/Vect cells, whereas no such events were observed in the HL-60/FAK cells. In particular, the expression of procaspase-8 gene and subsequent cleavage of caspase-8 were markedly reduced in HL-60/FAK cells, while expression of TRAIL-receptor 2 and 3, TRADD, and FADD was equivalent in both types of cells. In HL-60/FAK cells, the phosphoinositide 3 (PI3)-kinase/Akt survival pathway was constitutively activated, accompanied by significant induction of inhibitor-of-apoptosis proteins, XIAP, RIP, and Bcl-XL. The introduction of FAK siRNA in HL-60/FAK cells sensitized them against TRAIL-induced apoptosis, confirming that overexpressed FAK downregulates procaspase-8 expression, which subsequently inhibits downstream apoptosis pathway in the HL-60/FAK cells

  6. Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System.

    Science.gov (United States)

    Gennaro, Mariangela; Mattiello, Alessandro; Mazziotti, Raffaele; Antonelli, Camilla; Gherardini, Lisa; Guzzetta, Andrea; Berardi, Nicoletta; Cioni, Giovanni; Pizzorusso, Tommaso

    2017-01-01

    Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a "maladaptive" strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke.

  7. High cut-off haemodialysis induces remission of recurrent idiopathic focal segmental glomerulosclerosis after renal transplantation but is no alternative to plasmapheresis

    NARCIS (Netherlands)

    I. Noorlander (Iris); D.A. Hesselink (Dennis); M. Wabbijn (Marike); M.G.H. Betjes (Michiel)

    2011-01-01

    textabstractA 26-year-old male experienced a recurrence of idiopathic focal segmental glomerulosclerosis (iFSGS) after his second renal transplant. Reduction of proteinuria was rapidly induced by plasmapheresis (PP) and the patient has remained in remission with a once-weekly PP regimen, which has

  8. Focal epilepsy presenting as a bath-induced paroxysmal event/breath-holding attack

    OpenAIRE

    Stutchfield, C.J.; Loh, N.R.

    2014-01-01

    Bath-induced paroxysmal events in infants and children can be triggered by various etiologies, including cardiological, neurological, and metabolic causes. It is important to ascertain the underlying cause for such events as this significantly affects the child's management and prognosis. We present the case of a 19-month-old boy who presented with recurrent episodes of apnea, cyanosis, and reduced level of consciousness in response to bathing. Through detailed history and investigation, the ...

  9. Myosin X is recruited to nascent focal adhesions at the leading edge and induces multi-cycle filopodial elongation.

    Science.gov (United States)

    He, Kangmin; Sakai, Tsuyoshi; Tsukasaki, Yoshikazu; Watanabe, Tomonobu M; Ikebe, Mitsuo

    2017-10-20

    Filopodia protrude from the leading edge of cells and play important roles in cell motility. Here we report the mechanism of myosin X (encoded by Myo10)-induced multi-cycle filopodia extension. We found that actin, Arp2/3, vinculin and integrin-β first accumulated at the cell's leading edge. Myosin X was then gathered at these sites, gradually clustered by lateral movement, and subsequently initiated filopodia formation. During filopodia extension, we found the translocation of Arp2/3 and integrin-β along filopodia. Arp2/3 and integrin-β then became localized at the tip of filopodia, from where myosin X initiated the second extension of filopodia with a change in extension direction, thus producing long filopodia. Elimination of integrin-β, Arp2/3 and vinculin by siRNA significantly attenuated the myosin-X-induced long filopodia formation. We propose the following mechanism. Myosin X accumulates at nascent focal adhesions at the cell's leading edge, where myosin X promotes actin convergence to create the base of filopodia. Then myosin X moves to the filopodia tip and attracts integrin-β and Arp2/3 for further actin nucleation. The tip-located myosin X then initiates the second cycle of filopodia elongation to produce the long filopodia.

  10. Hyperthermia induced after recirculation triggers chronic neurodegeneration in the penumbra zone of focal ischemia in the rat brain

    Directory of Open Access Journals (Sweden)

    L.A. Favero-Filho

    2008-11-01

    Full Text Available Chronic neurodegenerative processes have been identified in the rat forebrain after prolonged survival following hyperthermia (HT initiated a few hours after transient global ischemia. Since transient global ischemia and ischemic penumbra share pathophysiological similarities, this study addressed the effects of HT induced after recirculation of focal brain ischemia on infarct size during long survival times. Adult male Wistar rats underwent intra-luminal occlusion of the left middle cerebral artery for 60 min followed by HT (39.0-39.5°C or normothermia. Control procedures included none and sham surgery with and without HT, and middle cerebral artery occlusion alone. Part I: 6-h HT induced at recirculation. Part II: 2-h HT induced at 2-, 6-, or 24-h recirculation. Part III: 2-h HT initiated at recirculation or 6-h HT initiated at 2-, 6- or 24-h recirculation. Survival periods were 7 days, 2 or 6 months. The effects of post-ischemic HT on cortex and striatum were evaluated histopathologically by measuring the area of remaining tissue in the infarcted hemisphere at -0.30 mm from bregma. Six-hour HT initiated from 6-h recirculation caused a significant decrease in the remaining cortical tissue between 7-day (N = 8 and 2-month (N = 8 survivals (98.46 ± 1.14 to 73.62 ± 8.99%, respectively. When induced from 24-h recirculation, 6-h HT caused a significant reduction of the remaining cortical tissue between 2- (N = 8 and 6-month (N = 9 survivals (94.97 ± 5.02 vs 63.26 ± 11.97%, respectively. These data indicate that post-ischemic HT triggers chronic neurodegenerative processes in ischemic penumbra, suggesting that similar fever-triggered effects may annul the benefit of early recirculation in stroke patients over the long-term.

  11. Recurrent Bilateral Focal Myositis.

    Science.gov (United States)

    Nagafuchi, Hiroko; Nakano, Hiromasa; Ooka, Seido; Takakuwa, Yukiko; Yamada, Hidehiro; Tadokoro, Mamoru; Shimojo, Sadatomo; Ozaki, Shoichi

    This report describes a rare case of recurrent bilateral focal myositis and its successful treatment via methotrexate. A 38-year-old man presented myalgia of the right gastrocnemius in May 2005. Magnetic resonance imaging showed very high signal intensity in the right gastrocnemius on short-tau inversion recovery images. A muscle biopsy revealed inflammatory CD4+ cell-dominant myogenic change. Focal myositis was diagnosed. The first steroid treatment was effective. Tapering of prednisolone, however, repeatedly induced myositis relapse, which progressed to multiple muscle lesions of both lower limbs. Initiation of methotrexate finally allowed successful tapering of prednisolone, with no relapse in the past 4 years.

  12. Experimental Focal Cerebral Ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas

    2007-01-01

    Focal cerebral ischemia due to occlusion of a major cerebral artery is the cause of ischemic stroke which is a major reason of mortality, morbidity and disability in the populations of the developed countries. In the seven studies summarized in the thesis focal ischemia in rats induced by occlusion...... in the penumbra is recruited in the infarction process leading to a progressive growth of the infarct. The penumbra hence constitutes an important target for pharmacological treatment because of the existence of a therapeutic time window during which treatment with neuroprotective compounds may prevent...

  13. Facilitated beam-walking recovery during acute phase by kynurenic acid treatment in a rat model of photochemically induced thrombosis causing focal cerebral ischemia.

    Science.gov (United States)

    Abo, Masahiro; Yamauchi, Hideki; Suzuki, Masahiko; Sakuma, Mio; Urashima, Mitsuyoshi

    We previously demonstrated the presence of activated areas in the non-injured contralateral sensorimotor cortex in addition to the ipsilateral sensorimotor cortex of the area surrounding a brain infarction, using a rat model of focal photochemically induced thrombosis (PIT) and functional magnetic resonance imaging. Using this model, we next applied gene expression profiling to screen key molecules upregulated in the activated area. RNA was extracted from the ipsilateral and contralateral sensorimotor cortex to the focal brain infarction and from the sham controlled cortex, and hybridized to gene-expression profiling arrays containing 1,322 neurology-related genes. Results showed that glycine receptors were upregulated in both the ipsilateral and contralateral cortex to the focal ischemic lesion. To prove the preclinical significance of upregulated glycine receptors, kynurenic acid, an endogenous antagonist to glycine receptors on neuronal cells, was administered intrathecally. As a result, the kynurenic acid significantly improved behavioral recovery within 10 days from paralysis induced by the focal PIT (p beam walking. These results suggest that intrathecal administration of a glycine receptor antagonist may facilitate behavioral recovery during the acute phase after brain infarction. Copyright (c) 2006 S. Karger AG, Basel.

  14. Stimuli of sensory-motor nerves terminate arterial contractile effects of endothelin-1 by CGRP and dissociation of ET-1/ET(A)-receptor complexes

    DEFF Research Database (Denmark)

    Meens, Merlijn J P M T; Compeer, Matthijs G; Hackeng, Tilman M

    2010-01-01

    of the antagonists and (ii) can be selectively dissociated by an endogenous counterbalancing mechanism. METHODOLOGY/PRINCIPAL FINDINGS: In isolated rat mesenteric resistance arteries, ET(A)-antagonists, endothelium-derived relaxing factors and synthetic vasodilators transiently reduced contractile effects of ET-1......BACKGROUND: Endothelin-1 (ET-1), a long-acting paracrine mediator, is implicated in cardiovascular diseases but clinical trials with ET-receptor antagonists were not successful in some areas. We tested whether the quasi-irreversible receptor-binding of ET-1 (i) limits reversing effects...... but did not prevent persistent effects of the peptide. Stimuli of peri-vascular vasodilator sensory-motor nerves such as capsaicin not only reduced but also terminated long-lasting effects of ET-1. This was prevented by CGRP-receptor antagonists and was mimicked by exogenous calcitonin gene...

  15. Identification of chronic heart failure patients with a high 12-month mortality risk using biomarkers including plasma C-terminal pro-endothelin-1.

    Directory of Open Access Journals (Sweden)

    Ewa A Jankowska

    Full Text Available OBJECTIVES: We hypothesised that assessment of plasma C-terminal pro-endothelin-1 (CT-proET-1, a stable endothelin-1 precursor fragment, is of prognostic value in patients with chronic heart failure (CHF, beyond other prognosticators, including N-terminal pro-B-type natriuretic peptide (NT-proBNP. METHODS: We examined 491 patients with systolic CHF (age: 63±11 years, 91% men, New York Heart Association [NYHA] class [I/II/III/IV]: 9%/45%/38%/8%, 69% ischemic etiology. Plasma CT-proET-1 was detected using a chemiluminescence immunoassay. RESULTS: Increasing CT-proET-1 was a predictor of increased cardiovascular mortality at 12-months of follow-up (standardized hazard ratio 1.42, 95% confidence interval [CI] 1.04-1.95, p = 0.03 after adjusting for NT-proBNP, left ventricular ejection fraction (LVEF, age, creatinine, NYHA class. In receiver operating characteristic curve analysis, areas under curve for 12-month follow-up were similar for CT-proET-1 and NT-proBNP (p = 0.40. Both NT-proBNP and CT-proET-1 added prognostic value to a base model that included LVEF, age, creatinine, and NYHA class. Adding CT-proET-1 to the base model had stronger prognostic power (p<0.01 than adding NT-proBNP (p<0.01. Adding CT-proET-1 to NT-proBNP in this model yielded further prognostic information (p = 0.02. CONCLUSIONS: Plasma CT-proET-1 constitutes a novel predictor of increased 12-month cardiovascular mortality in patients with CHF. High CT-proET-1 together with high NT-proBNP enable to identify patients with CHF and particularly unfavourable outcomes.

  16. Serial alterations in digital hemodynamics and endothelin-1 immunoreactivity, platelet-neutrophil aggregation, and concentrations of nitric oxide, insulin, and glucose in blood obtained from horses following carbohydrate overload.

    Science.gov (United States)

    Eades, Susan C; Stokes, Ashley M; Johnson, Philip J; LeBlanc, Casey J; Ganjam, Venkataseshu K; Buff, Preston R; Moore, Rustin M

    2007-01-01

    To quantify changes in endothelium-derived factors and relate those changes to various aspects of digital hemodynamics during the prodromal stages of carbohydrate overload (CHO)-induced laminitis in horses. 20 adult horses without abnormalities of the digit. Digital and jugular venous blood samples were collected at 1-hour intervals (for assessment of endothelin-1 [ET-1] immunoreactivity and measurement of glucose, insulin, and nitric oxide [NO] concentrations) or 4-hour intervals (CBC and platelet-neutrophil aggregate assessment) for 8 hours or 16 hours after induction of CHO-associated laminitis in horses treated with an ET-1 antagonist. Effects of treatment, collection site, and time and the random effects of horse on each variable were analyzed by use of a repeated-measures model. Where treatment and collection site had no significant effect, data were combined. Compared with baseline values, CHO resulted in changes in several variables, including a significant increase from baseline in digital blood ET-like immunoreactivity at 11 hours; digital blood ET-like immunoreactivity was significantly greater than that in jugular venous blood at 8, 9, 11, and 12 hours. Digital and jugular venous blood concentrations of glucose increased from baseline significantly at 3, 4, and 5 hours; insulin concentration increased significantly at 5 hours; and the number of platelet-neutrophil aggregates increased significantly at 12 hours. In horses, concurrent increases in venous blood ET-1 immunoreactivity, insulin and glucose concentrations, and platelet-neutrophil aggregates support a role of endothelial dysfunction in the pathogenesis of CHO-induced laminitis.

  17. Aquaporin-4 inhibition mediates piroxicam-induced neuroprotection against focal cerebral ischemia/reperfusion injury in rodents.

    Science.gov (United States)

    Bhattacharya, Pallab; Pandey, Anand Kumar; Paul, Sudip; Patnaik, Ranjana; Yavagal, Dileep R

    2013-01-01

    Aquaporin-4(AQP4) is an abundant water channel protein in brain that regulates water transport to maintain homeostasis. Cerebral edema resulting from AQP4 over expression is considered to be one of the major determinants for progressive neuronal insult during cerebral ischemia. Although, both upregulation and downregulation of AQP4 expression is associated with brain pathology, over expression of AQP4 is one of the chief contributors of water imbalance in brain during ischemic pathology. We have found that Piroxicam binds to AQP4 with optimal binding energy value. Thus, we hypothesized that Piroxicam is neuroprotective in the rodent cerebral ischemic model by mitigating cerebral edema via AQP4 regulation. Rats were treated with Piroxicam OR placebo at 30 min prior, 2 h post and 4 h post 60 minutes of MCAO followed by 24 hour reperfusion. Rats were evaluated for neurological deficits and motor function just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, biochemical analysis, RT-PCR and western blot experiments. Piroxicam pretreatment thirty minutes prior to ischemia and four hour post reperfusion afforded neuroprotection as evident through significant reduction in cerebral infarct volume, improvement in motor behavior, neurological deficit and reduction in brain edema. Furthermore, ischemia induced surge in levels of nitrite and malondialdehyde were also found to be significantly reduced in ischemic brain regions in treated animals. This neuroprotection was found to be associated with inhibition of acid mediated rise in intracellular calcium levels and also downregulated AQP4 expression. Findings of the present study provide significant evidence that Piroxicam acts as a potent AQP4 regulator and renders neuroprotection in focal cerebral ischemia. Piroxicam could be clinically exploited for the treatment of brain stroke along with other anti-stroke therapeutics in future.

  18. Enhanced expression of Gqα and PLC-β1 proteins contributes to vascular smooth muscle cell hypertrophy in SHR: role of endogenous angiotensin II and endothelin-1.

    Science.gov (United States)

    Atef, Mohammed Emehdi; Anand-Srivastava, Madhu B

    2014-07-01

    Vascular Gqα signaling has been shown to contribute to cardiac hypertrophy. In addition, angiotensin II (ANG II) was shown to induce vascular smooth muscle cell (VSMC) hypertrophy through Gqα signaling; however, the studies on the role of Gqα and PLC-β1 proteins in VSMC hypertrophy in animal model are lacking. The present study was therefore undertaken to examine the role of Gqα/PLC-β1 proteins and the signaling pathways in VSMC hypertrophy using spontaneously hypertensive rats (SHR). VSMC from 16-wk-old SHR and not from 12-wk-old SHR exhibited enhanced levels of Gqα/PLC-β1 proteins compared with age-matched Wistar-Kyoto (WKY) rats as determined by Western blotting. However, protein synthesis as determined by [(3)H]leucine incorporation was significantly enhanced in VSMC from both 12- and 16-wk-old SHR compared with VSMC from age-matched WKY rats. Furthermore, the knockdown of Gqα/PLC-β1 in VSMC from 16-wk-old SHR by antisense and small interfering RNA resulted in attenuation of protein synthesis. In addition, the enhanced expression of Gqα/PLC-β1 proteins, enhanced phosphorylation of ERK1/2, and enhanced protein synthesis in VSMC from SHR were attenuated by the ANG II AT1 and endothelin-1 (ET-1) ETA receptor antagonists losartan and BQ123, respectively, but not by the ETB receptor antagonist BQ788. In addition, PD98059 decreased the enhanced expression of Gqα/PLC-β1 and protein synthesis in VSMC from SHR. These results suggest that the enhanced levels of endogenous ANG II and ET-1 through the activation of AT1 and ETA receptors, respectively, and MAP kinase signaling, enhanced the expression of Gqα/PLC-β1 proteins in VSMC from 16-wk-old SHR and result in VSMC hypertrophy. Copyright © 2014 the American Physiological Society.

  19. Inflammatory Murine Skin Responses to UV-B Light Are Partially Dependent on Endothelin-1 and Mast Cells

    OpenAIRE

    Metz, Martin; Lammel, Verena; Gibbs, Bernhard F.; Maurer, Marcus

    2006-01-01

    Endothelin (ET-1) has been shown to crucially contribute to UV-induced skin responses such as tanning. To test whether ET-1 is also involved in early cutaneous reactions to UV, we assessed ET-1 skin levels in UV-irradiated mice. In correlation with the levels of UV-induced skin inflammation, ET-1 concentrations increased substantially and continually. Moreover, blocking of ET-1 receptors (ETA) resulted in significantly decreased cutaneous inflammation following UV irradiation. When we assesse...

  20. Phosphatidylinositol 4,5-bisphosphate triggers activation of focal adhesion kinase by inducing clustering and conformational changes

    DEFF Research Database (Denmark)

    Goñi, Guillermina M; Epifano, Carolina; Boskovic, Jasminka

    2014-01-01

    Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase (NRTK) with key roles in integrating growth and cell matrix adhesion signals, and FAK is a major driver of invasion and metastasis in cancer. Cell adhesion via integrin receptors is well known to trigger FAK signaling, and many of the p...

  1. The Effects of Repeated Rehabilitation “Tune-Ups” on Functional Recovery After Focal Ischemia in Rats

    DEFF Research Database (Denmark)

    Clarke, Jared; Rytter, Hana Malá; Windle, Victoria

    2009-01-01

    of stroke recovery. Methods. Rats were exposed to focal ischemia (endothelin-1 applied to forelimb sensorimotor cortex and dorsolateral striatum) and allowed to recover either in standard housing or in a combination of enriched environment and rehabilitative reaching for 9 weeks. Animals were then exposed...... complexity in the contralesional forelimb motor cortex. Results. Although early enriched rehabilitation significantly improved sensorimotor function in both the beam and staircase tests, “tune-up” therapy had no effect on recovery. Golgi–Cox analysis revealed no effect of treatment on dendritic complexity...

  2. Endothelin-1 and endothelin-2 initiate and maintain contractile responses by different mechanisms in rat mesenteric and cerebral arteries

    DEFF Research Database (Denmark)

    Compeer, M. G.; Janssen, G. M. J.; De Mey, J. G. R.

    2013-01-01

    , but relaxed ET-1-induced contractions in MRA. A PLC inhibitor prevented contractile responses to ET-1 and ET-2 in MRA and BA, and relaxed ET-1- and ET-2-induced responses in MRA and ET-1 effects in BA. A Rho-kinase inhibitor did not modify sensitivity, maximum and maintenance of responses to both peptides...... in both arteries but relaxed ET-2, but not ET-1, effects in MRA and ET-1 effects in BA. Conclusions and ImplicationsPLC played a key role in arterial contractile responses to ETs, but ET-1 and ET-2 initiated and maintained vasoconstriction through different mechanisms, and these differed between MRA...

  3. Stimuli of sensory-motor nerves terminate arterial contractile effects of endothelin-1 by CGRP and dissociation of ET-1/ET(A-receptor complexes.

    Directory of Open Access Journals (Sweden)

    Merlijn J P M T Meens

    Full Text Available BACKGROUND: Endothelin-1 (ET-1, a long-acting paracrine mediator, is implicated in cardiovascular diseases but clinical trials with ET-receptor antagonists were not successful in some areas. We tested whether the quasi-irreversible receptor-binding of ET-1 (i limits reversing effects of the antagonists and (ii can be selectively dissociated by an endogenous counterbalancing mechanism. METHODOLOGY/PRINCIPAL FINDINGS: In isolated rat mesenteric resistance arteries, ET(A-antagonists, endothelium-derived relaxing factors and synthetic vasodilators transiently reduced contractile effects of ET-1 but did not prevent persistent effects of the peptide. Stimuli of peri-vascular vasodilator sensory-motor nerves such as capsaicin not only reduced but also terminated long-lasting effects of ET-1. This was prevented by CGRP-receptor antagonists and was mimicked by exogenous calcitonin gene-related peptide (CGRP. Using 2-photon laser scanning microscopy in vital intact arteries, capsaicin and CGRP, but not ET(A-antagonism, were observed to promote dissociation of pre-existing ET-1/ET(A-receptor complexes. CONCLUSIONS: Irreversible binding and activation of ET(A-receptors by ET-1 (i occur at an antagonist-insensitive site of the receptor and (ii are selectively terminated by endogenously released CGRP. Hence, natural stimuli of sensory-motor nerves that stimulate release of endogenous CGRP can be considered for therapy of diseases involving ET-1.

  4. Differential Impact of Stress Reduction Programs upon Ambulatory Blood Pressure among African American Adolescents: Influences of Endothelin-1 Gene and Chronic Stress Exposure

    Directory of Open Access Journals (Sweden)

    Mathew J. Gregoski

    2012-01-01

    Full Text Available Stress-activated gene × environment interactions may contribute to individual variability in blood pressure reductions from behavioral interventions. We investigated effects of endothelin-1 (ET-1 LYS198ASN SNP and discriminatory stress exposure upon impact of 12-week behavioral interventions upon ambulatory BP (ABP among 162 prehypertensive African American adolescents. Following genotyping, completion of questionnaire battery, and 24-hour ABP monitoring, participants were randomized to health education control (HEC, life skills training (LST, or breathing awareness meditation (BAM. Postintervention ABP was obtained. Significant three-way interactions on ABP changes indicated that among ET-1 SNP carriers, the only group to show reductions was BAM from low chronic stress environments. Among ET-1 SNP noncarriers, under low chronic stress exposure, all approaches worked, especially BAM. Among high stress exposure noncarriers, only BAM resulted in reductions. If these preliminary findings are replicated via ancillary analyses of archival databases and then via efficacy trials, selection of behavioral prescriptions for prehypertensives will be edging closer to being guided by individual's underlying genetic and environmental factors incorporating the healthcare model of personalized preventive medicine.

  5. Increased endothelin-1 and diminished nitric oxide levels in blister fluids of patients with intermediate cold type complex regional pain syndrome type 1

    Directory of Open Access Journals (Sweden)

    Niehof Sjoerd

    2006-11-01

    Full Text Available Abstract Background In complex regional pain syndrome type 1 (CRPS1 pro-inflammatory mediators and vascular changes play an important role in the sustained development and outcome of the disease. The aim of this study was to determine the involvement of vasoactive substances endothelin-1 (ET-1 and nitric oxide (NO during early chronic CRPS1. Methods Included were 29 patients with CRPS 1 who were diagnosed during the acute stage of their disease and observed during follow-up visits. Disease activity and impairment were determined and artificial suction blisters were made on the CRPS1 and the contralateral extremities for measurements of IL-6, TNF-α, ET-1 and nitrate/nitrite (NOx. Results The levels of IL-6, TNF-α and ET-1 in blister fluid in the CRPS1 extremity versus the contralateral extremity were significantly increased and correlated with each other, whereas NOx levels were decreased. Conclusion The NOx/ET-1 ratio appears to be disturbed in the intermediate stage of CRPS, resulting in vasoconstriction and consequently in a diminished tissue blood distribution.

  6. Genetic Polymorphisms in Endothelin-1 as Predictors for Long-Term Survival and the Cardiac Index in Patients Undergoing On-Pump Cardiac Surgery.

    Directory of Open Access Journals (Sweden)

    Ashham Mansur

    Full Text Available Genetic variants within the endothelin-1 gene (EDN1 have been associated with several cardiovascular diseases and may act as genetic prognostic markers. Here, we explored the overall relevance of EDN1 polymorphisms for long-term survival in patients undergoing on-pump cardiac surgery. A prospectively collected cohort of 455 Caucasian patients who underwent cardiac surgery with cardiopulmonary bypass was followed up for 5 years. The obtained genotypes and inferred haplotypes were analyzed for their associations with the five-year mortality rate (primary endpoint. The EDN1 T-1370G and K198N genotype distributions did not deviate from Hardy-Weinberg equilibrium and the major allele frequencies were 83% and 77%, respectively. The cardiovascular risk factors were equally distributed in terms of the different genotypes and haplotypes associated with the two polymorphisms. The five-year mortality rate did not differ among the different EDN1 T-1370G and K198N genotypes and haplotypes. Haplotype analysis revealed that carriers of the G-T (compound EDN1 T-1370G G/K198N T haplotype had a higher cardiac index than did non-carriers (p = 0.0008; however, this difference did not reach significance after adjusting for multiple testing. The results indicate that common variations in EDN1 do not act as prognostic markers for long-term survival in patients undergoing on-pump cardiac surgery.

  7. Stimuli of Sensory-Motor Nerves Terminate Arterial Contractile Effects of Endothelin-1 by CGRP and Dissociation of ET-1/ETA-Receptor Complexes

    Science.gov (United States)

    Meens, Merlijn J. P. M. T.; Compeer, Matthijs G.; Hackeng, Tilman M.; van Zandvoort, Marc A.; Janssen, Ben J. A.; De Mey, Jo G. R.

    2010-01-01

    Background Endothelin-1 (ET-1), a long-acting paracrine mediator, is implicated in cardiovascular diseases but clinical trials with ET-receptor antagonists were not successful in some areas. We tested whether the quasi-irreversible receptor-binding of ET-1 (i) limits reversing effects of the antagonists and (ii) can be selectively dissociated by an endogenous counterbalancing mechanism. Methodology/Principal findings In isolated rat mesenteric resistance arteries, ETA-antagonists, endothelium-derived relaxing factors and synthetic vasodilators transiently reduced contractile effects of ET-1 but did not prevent persistent effects of the peptide. Stimuli of peri-vascular vasodilator sensory-motor nerves such as capsaicin not only reduced but also terminated long-lasting effects of ET-1. This was prevented by CGRP-receptor antagonists and was mimicked by exogenous calcitonin gene-related peptide (CGRP). Using 2-photon laser scanning microscopy in vital intact arteries, capsaicin and CGRP, but not ETA-antagonism, were observed to promote dissociation of pre-existing ET-1/ETA-receptor complexes. Conclusions Irreversible binding and activation of ETA-receptors by ET-1 (i) occur at an antagonist-insensitive site of the receptor and (ii) are selectively terminated by endogenously released CGRP. Hence, natural stimuli of sensory-motor nerves that stimulate release of endogenous CGRP can be considered for therapy of diseases involving ET-1. PMID:20532232

  8. Intraportal nicotine infusion in rats decreases hepatic blood flow through endothelin-1 and both endothelin A and endothelin B receptors

    International Nuclear Information System (INIS)

    Hashimoto, Takashi; Yoneda, Masashi; Shimada, Tadahito; Kurosawa, Mieko; Terano, Akira

    2004-01-01

    Smoking has been demonstrated to aggravate liver injury. Nicotine, a major pharmacological component of tobacco smoke, affects a multitude of functions. Smoking and nicotine induce synthesis of endothelin (ET)-1. The effect of intraportal infusion of nicotine on hepatic circulation and an involvement of ET-1 and ET receptor in the action of nicotine were investigated in rats. Nicotine (0-100 μg/kg/h) was infused into the portal vein of urethane-anesthetized rats, and changes of hepatic blood flow were evaluated. Intraportal infusion of nicotine dose-dependently decreased hepatic blood flow and increased portal pressure without any alteration of heart rate or arterial blood pressure. This action of intraportal nicotine was completely abolished by pretreatment of ET-1 antibody. Either BQ485 (ET A receptor antagonist) or BQ788 (ET B receptor antagonist) partially reversed the effect of nicotine, and combination of BQ788 and BQ485 completely abolished it. These findings suggest that nicotine inhibits hepatic circulation through ET-1, and ET A and ET B receptor

  9. Accumulation of GABAergic neurons, causing a focal ambient GABA gradient, and downregulation of KCC2 are induced during microgyrus formation in a mouse model of polymicrogyria.

    Science.gov (United States)

    Wang, Tianying; Kumada, Tatsuro; Morishima, Toshitaka; Iwata, Satomi; Kaneko, Takeshi; Yanagawa, Yuchio; Yoshida, Sachiko; Fukuda, Atsuo

    2014-04-01

    Although focal cortical malformations are considered neuronal migration disorders, their formation mechanisms remain unknown. We addressed how the γ-aminobutyric acid (GABA)ergic system affects the GABAergic and glutamatergic neuronal migration underlying such malformations. A focal freeze-lesion (FFL) of the postnatal day zero (P0) glutamic acid decarboxylase-green fluorescent protein knock-in mouse neocortex produced a 3- or 4-layered microgyrus at P7. GABAergic interneurons accumulated around the necrosis including the superficial region during microgyrus formation at P4, whereas E17.5-born, Cux1-positive pyramidal neurons outlined the GABAergic neurons and were absent from the superficial layer, forming cell-dense areas in layer 2 of the P7 microgyrus. GABA imaging showed that an extracellular GABA level temporally increased in the GABAergic neuron-positive area, including the necrotic center, at P4. The expression of the Cl(-) transporter KCC2 was downregulated in the microgyrus-forming GABAergic and E17.5-born glutamatergic neurons at P4; these cells may need a high intracellular Cl(-) concentration to induce depolarizing GABA effects. Bicuculline decreased the frequency of spontaneous Ca(2+) oscillations in these microgyrus-forming cells. Thus, neonatal FFL causes specific neuronal accumulation, preceded by an increase in ambient GABA during microgyrus formation. This GABA increase induces GABAA receptor-mediated Ca(2+) oscillation in KCC2-downregulated microgyrus-forming cells, as seen in migrating cells during early neocortical development.

  10. Chronic high-sodium diet increases aortic wall endothelin-1 expression in a blood pressure-independent fashion in rats.

    Science.gov (United States)

    Tsai, Yu-Hwai; Ohkita, Mamoru; Gariepy, Cheryl E

    2006-06-01

    Vascular endothelin (ET)-1 is upregulated in several forms of salt-induced hypertension. It is unclear to what extent these effects are primary or secondary to endothelial damage. We hypothesized that a high-sodium diet (HNa) increases vascular ET-1 production independent of arterial blood pressure changes. We investigated the effect of chronic HNa with and without ET(A) blockade on circulating and aortic ET-1 protein levels as well as aortic expression of ET-1 and ET(A) messenger RNA (mRNA) in inbred Wistar-Kyoto (WKY) and congenic ET(B)-deficient rats. Comparing WKY rats fed a low-sodium diet (LNa) with those fed HNa for 3 weeks, aortic wall ET-1 protein is significantly increased in response to HNa (331 +/- 43 pg/g tissue for LNa vs. 557 +/- 34 pg/gm tissue for HNa). HNa also increased aortic wall ET-1 mRNA levels by 40%, as determined by quantitative reverse transcriptase polymerase chain reaction. We then compared rats chronically treated with the ET(A)-selective antagonist, ABT-627, while receiving either LNa or HNa. There were no differences in arterial blood pressure (mean arterial pressure 89 +/- 1 mm Hg for WKY on LNa; 90 +/- 3 for WKY on HNa; 91 +/- 2 for ET(B)-deficient/ABT-627-treated on HNa) or heart rate. However, aortic wall ET-1 protein levels were 4-fold higher in the HNa group. Further, HNa increased aortic wall ET-1 mRNA (approximately 1.5- to 3-fold) and ET(A) mRNA (approximately 2- to 7-fold), independent of activation of ET(B). Therefore, the expression of ET-1 mRNA by the aortic wall is increased in response to chronic high dietary sodium in WKY rats in the absence of changes in arterial blood pressure.

  11. Interleukin 1β induces rapid phosphorylation and redistribution of talin: A possible mechanism for modulation of fibroblast focal adhesion

    International Nuclear Information System (INIS)

    Qwarnstroem, E.E.; MacFarlane, S.A.; Page, R.C.; Dower, S.K.

    1991-01-01

    The majority of interleukin 1 (IL-1) receptors in human fibroblasts has been shown to be localized at focal adhesions. This study describes rapid alterations caused by IL-1β/IL-1-receptor interaction at these sites. Fibroblast monolayers, incubated with IL-1β and prepared for electron microscopy, showed successive loss of cell-substratum contact and fewer and less-pronounced processes. Immunocytochemistry revealed loss and redistribution of the talin staining initially observed after 5-15 min of IL-1β incubation. Similarly, the cytoskeleton showed a decrease in staining and a disorganization starting from 15 to 30 min after IL-1 addition, whereas extracellular fibronectin appeared largely unaffected. Prelabeling with [ 32 P]phosphate showed a 2- to 3-fold increase in the level of talin phosphorylation, peaking at 15 min. Phospho amino acid analyses revealed a higher level of serine and threonine phosphorylation. The data suggest that the action of IL-1β on fibroblasts may be partially mediated by direct phosphorylation of talin via activation of a protein serine/threonine kinase, leading to changes in transmembrane linkage proteins and the cytoskeleton. Such alterations at focal adhesions may provide a mechanism by which IL-1 can rapidly modulate cell-matrix interactions during inflammation and wound healing

  12. Impact of the use of antibodies anti endothelin 1 on the coronary arterial estenosis for hyperplasia secondary neo intimal to barotraumas with ball and Stent in porcines

    International Nuclear Information System (INIS)

    Pineda V, Mauricio; Maldonado, Luz A; Uribe, Ana Maria and others

    2003-01-01

    Coronary angioplasty (PTCA) is performed in about two million surgical procedures every year in the world, and coronary restenosis (CR) continues to be it's weakest point. There are four mechanisms involved in CR 1. Thrombosis, 2.elastic recoil, 3. Constrictive arterial remodeling; and 4. Intimal hyperplasia. The first three are managed with Stents, inhibitors of GP lib//iiia, antiagregants and anticoagulants. The fourth is believed to be the only responsible of post Stent CR. endothelin 1(ET1) produces cellular proliferation. Impact of the anti ET1 anti bodies by intra coronary injection, or generated by immune response at the subcutaneous (SC) application of ET1, on the NI growth in porcines, who have undergone barotrauma with Stent, is expected to be demonstrated. PTCA was performed in 12 pigs (36 arterial specimens). They were sacrificed after four weeks of follow up. Specimens were divided in three groups, previously randomized, resulting in 12 specimens a group. The placebo group received intracoronary infusion of saline solution immediately after the barotraumas. The second group received intracoronary infusion of AET1 antibodies and the third group received SC injection of ET1 fourteen days before the trauma. Segments were studied with IVUS and hystomotphometric analysis. Statistical analysis: it was performed by the student t in order to compare independent measures. Because of the small size of the groups, the Mann Whitney test was applied. A double tale analysis was performed in both cases. A significant reduction of the NI area was obtained both with the injection of AET1 Abs and ET1 SC (p 0.001) in the IVUS and the hystomotphometric analyses. AET1 antibodies seem to prevent the post Stent NI growth. There is no significant advantage between both forms of injection

  13. G-231A and G+70C polymorphisms of endothelin receptor type-A gene could affect the psoriasis area and severity index score and endothelin 1 levels

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    Gökhan Okan

    2015-01-01

    Full Text Available Background: The etiopathogenesis of psoriasis has not been clearly elucidated although the role of chronic inflammation, imbalance between pro- and anti-inflammatory cytokines, and many immunological events have been established. Endothelin 1 (EDN1 and endothelin receptor type-A (EDNRA are implicated in the inflammatory process. The relationships between EDN1 and EDNRA polymorphisms with several diseases have been found. Aims and Objectives: This study examined the possible association of EDN1 (G5665T and T-1370G and EDNRA (G-231A and G + 70C single nucleotide polymorphisms (SNPs with the occurence of psoriasis, and evaluated the relationship between genotypes and clinical/laboratory manifestation of psoriasis. Materials and Methods: We analyzed genotype and allele distributions of the above-mentioned polymorphisms in 151 patients with psoriasis and 152 healthy controls by real-time PCR combined with melting curve analysis. Results: We did not find significant differences in the genotype and allele distributions of EDN1 T-1370G, EDNRA G-231A, and EDNRA G+70C polymorphisms between patients with psoriasis and healthy controls. Psoriasis area and severity index (PASI score of EDNRA -231 polymorphic A allele carrying subjects (AA and AA + AG was higher than that of wild homozygotes (P = 0.044 and P = 0.027, respectively. In addition, EDN1 levels in EDNRA+70 polymorphic C allele carriers (CC + CG were elevated when compared with GG genotype; however, the difference was at borderline significance (P = 0.05. Conclusion: Although there were no associations between studied polymorphisms and psoriasis susceptibility, the PASI score and EDN1 levels seem to be affected by EDNRA G-231A and G + 70C polymorphisms.

  14. Endothelin 1 gene is not a major modifier of chronic kidney disease advancement among the autosomal dominant polycystic kidney disease patients

    Directory of Open Access Journals (Sweden)

    Annapareddy Shiva Nagendra Reddy

    2016-01-01

    Full Text Available Introduction: Autosomal dominant polycystic kidney disease (ADPKD is characterized by the presence of numerous cysts in the kidney and manifest with various renal and extra-renal complications leading to ESRD. Endothelin may contribute to various renal and extra-renal manifestations pointing to genetic and environmental modifying factors that alter the risk of developing chronic kidney disease (CKD in ADPKD. In the present study we investigated six genes coding for endothelin 1 (EDN1 tagging-single nucleotide polymorphisms (tag-SNPs to unravel the EDN1 gene modifier effect for renal disease progression in ADPKD. Materials and Methods: The tag-SNPs were genotyped using FRET-based KASPar method in 108 ADPKD patients and 119 healthy subjects. Cochran-Armitage trend test was used to determine the association between ADPKD and EDN1 tag-SNPs. Multivariate logistic regression analysis was performed to assess the effect of tag-SNPs on CKD progression. The relationship between different CKD stages and hypertension and their interaction Mantel-Haenszel stratified analysis was performed. Results: All loci are polymorphic and followed Hardy-Weinberg equilibrium. Distribution of EDN1 genotypes and haplotypes in control and ADPKD is not statistically significant. Five SNPs covering 3.4 kb forming single LD block, but the LD was not strong between SNPs. The EDN1 genotypes are not contributing to the CKD advancement among the ADPKD patients. Conclusion: These results suggest that the EDN1 gene is not a major modifier of CKD advancement among ADPKD patients.

  15. Characterizing the role of endothelin-1 in the progression of cardiac hypertrophy in aryl hydrocarbon receptor (AhR) null mice

    International Nuclear Information System (INIS)

    Lund, Amie K.; Goens, M. Beth; Nunez, Bethany A.; Walker, Mary K.

    2006-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor characterized to play a role in detection and adaptation to environmental stimuli. Genetic deletion of AhR results in hypertension, and cardiac hypertrophy and fibrosis, associated with elevated plasma angiotensin II (Ang II) and endothelin-1 (ET-1), thus AhR appears to contribute to cardiovascular homeostasis. In these studies, we tested the hypothesis that ET-1 mediates cardiovascular pathology in AhR null mice via ET A receptor activation. First, we determine the time courses of cardiac hypertrophy, and of plasma and tissue ET-1 expression in AhR wildtype and null mice. AhR null mice exhibited increases in heart-to-body weight ratio and age-related expression of cardiac hypertrophy markers, β-myosin heavy chain (β-MHC), and atrial natriuretic factor (ANF), which were significant at 2 months. Similarly, plasma and tissue ET-1 expression was significantly elevated at 2 months and increased further with age. Second, AhR null mice were treated with ET A receptor antagonist, BQ-123 (100 nmol/kg/day), for 7, 28, or 58 days and blood pressure, cardiac fibrosis, and cardiac hypertrophy assessed, respectively. BQ-123 for 7 days significantly reduced mean arterial pressure in conscious, catheterized mice. BQ-123 for 28 days significantly reduced the histological appearance of cardiac fibrosis. Treatment for 58 days significantly reduced cardiac mass, assessed by heart weight, echocardiography, and β-MHC and ANF expression; and reduced cardiac fibrosis as determined by osteopontin and collagen I mRNA expression. These findings establish ET-1 and the ET A receptor as primary determinants of hypertension and cardiac pathology in AhR null mice

  16. Association studies suggest a key role for endothelin-1 in the pathogenesis of preeclampsia and the accompanying renin-angiotensin-aldosterone system suppression.

    Science.gov (United States)

    Verdonk, Koen; Saleh, Langeza; Lankhorst, Stephanie; Smilde, J E Ilse; van Ingen, Manon M; Garrelds, Ingrid M; Friesema, Edith C H; Russcher, Henk; van den Meiracker, Anton H; Visser, Willy; Danser, A H Jan

    2015-06-01

    Women with preeclampsia display low renin-angiotensin-aldosterone system activity and a high antiangiogenic state, the latter characterized by high levels of soluble Fms-like tyrosine kinase (sFlt)-1 and reduced placental growth factor levels. To investigate whether renin-angiotensin-aldosterone system suppression in preeclampsia is because of this disturbed angiogenic balance, we measured mean arterial pressure, creatinine, endothelin-1 (ET-1), and renin-angiotensin-aldosterone system components in pregnant women with a high (≥85; n=38) or low (<85; n=65) soluble Fms-like tyrosine kinase-1/placental growth factor ratio. Plasma ET-1 levels were increased in women with a high ratio, whereas their plasma renin activity and plasma concentrations of renin, angiotensinogen, and aldosterone were decreased. Plasma renin activity-aldosterone relationships were identical in both the groups. Multiple regression analysis revealed that plasma renin concentration correlated independently with mean arterial pressure and plasma ET-1. Plasma ET-1 correlated positively with soluble Fms-like tyrosine kinase-1 and negatively with plasma renin concentration, and urinary protein correlated with plasma ET-1 and mean arterial pressure. Despite the lower plasma levels of renin and angiotensinogen in the high-ratio group, their urinary levels of these components were elevated. Correction for albumin revealed that this was because of increased glomerular filtration. Subcutaneous arteries obtained from patients with preeclampsia displayed an enhanced, AT2 receptor-mediated response to angiotensin II. In conclusion, a high antiangiogenic state associates with ET-1 activation, which together with the increased mean arterial pressure may underlie the parallel reductions in renin and aldosterone in preeclampsia. Because ET-1 also was a major determinant of urinary protein, our data reveal a key role for ET-1 in the pathogenesis of preeclampsia. Finally, the enhanced angiotensin responsiveness

  17. Improvement of stance control and muscle performance induced by focal muscle vibration in young-elderly women: a randomized controlled trial.

    Science.gov (United States)

    Filippi, Guido M; Brunetti, Orazio; Botti, Fabio M; Panichi, Roberto; Roscini, Mauro; Camerota, Filippo; Cesari, Matteo; Pettorossi, Vito E

    2009-12-01

    Filippi GM, Brunetti O, Botti FM, Panichi R, Roscini M, Camerota F, Cesari M, Pettorossi VE. Improvement of stance control and muscle performance induced by focal muscle vibration in young-elderly women: a randomized controlled trial. To determine the effect of a particular protocol of mechanical vibration, applied focally and repeatedly (repeated muscle vibration [rMV]) on the quadriceps muscles, on stance and lower-extremity muscle power of young-elderly women. Double-blind randomized controlled trial; 3-month follow-up after intervention. Human Physiology Laboratories, University of Perugia, Italy. Sedentary women volunteers (N=60), randomized in 3 groups (mean age +/- SD, 65.3+/-4.2y; range, 60-72). rMV (100Hz, 300-500microm, in three 10-minute sessions a day for 3 consecutive days) was applied to voluntary contracted quadriceps (vibrated and contracted group) and relaxed quadriceps (vibrated and relaxed group). A third group received placebo stimulation (nonvibrated group). Area of sway of the center of pressure, vertical jump height, and leg power. Twenty-four hours after the end of the complete series of applications, the area of sway of the center of pressure decreased significantly by approximately 20%, vertical jump increased by approximately 55%, and leg power increased by approximately 35%. These effects were maintained for at least 90 days after treatment. rMV is a short-lasting and noninvasive protocol that can significantly and persistently improve muscle performance in sedentary young-elderly women.

  18. Matriptase is required for the active form of hepatocyte growth factor induced Met, focal adhesion kinase and protein kinase B activation on neural stem/progenitor cell motility.

    Science.gov (United States)

    Fang, Jung-Da; Lee, Sheau-Ling

    2014-07-01

    Hepatocyte growth factor (HGF) is a chemoattractant and inducer for neural stem/progenitor (NS/P) cell migration. Although the type II transmembrane serine protease, matriptase (MTP) is an activator of the latent HGF, MTP is indispensable on NS/P cell motility induced by the active form of HGF. This suggests that MTP's action on NS/P cell motility involves mechanisms other than proteolytic activation of HGF. In the present study, we investigate the role of MTP in HGF-stimulated signaling events. Using specific inhibitors of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt) or focal adhesion kinase (FAK), we demonstrated that in NS/P cells HGF-activated c-Met induces PI3k-Akt signaling which then leads to FAK activation. This signaling pathway ultimately induces MMP2 expression and NS/P cell motility. Knocking down of MTP in NS/P cells with specific siRNA impaired HGF-stimulation of c-Met, Akt and FAK activation, blocked HGF-induced production of MMP2 and inhibited HGF-stimulated NS/P cell motility. MTP-knockdown NS/P cells cultured in the presence of recombinant protein of MTP protease domain or transfected with the full-length wild-type but not the protease-defected MTP restored HGF-responsive events in NS/P cells. In addition to functioning as HGF activator, our data revealed novel function of MTP on HGF-stimulated c-Met signaling activation. Copyright © 2014. Published by Elsevier B.V.

  19. Inhibition of cell migration by focal adhesion kinase: Time-dependent difference in integrin-induced signaling between endothelial and hepatoblastoma cells.

    Science.gov (United States)

    Yu, Hongchi; Gao, Min; Ma, Yunlong; Wang, Lijuan; Shen, Yang; Liu, Xiaoheng

    2018-05-01

    angiogenesis plays an important role in the development and progression of tumors, and it involves a series of signaling pathways contributing to the migration of endothelial cells for vascularization and to the invasion of cancer cells for secondary tumor formation. Among these pathways, the focal adhesion kinase (FAK) signaling cascade has been implicated in a variety of human cancers in connection with cell adhesion and migration events leading to tumor angiogenesis, metastasis and invasion. Therefore, the inhibition of FAK in endothelial and/or cancer cells is a potential target for anti‑angiogenic therapy. In the present study, a small‑molecule FAK inhibitor, 1,2,4,5-benzenetetramine tetrahydrochloride (Y15), was used to study the effects of FAK inhibition on the adhesion and migration behaviors of vascular endothelial cells (VECs) and human hepatoblastoma cells. Furthermore, the time-dependent differences in proteins associated with the integrin-mediated FAK/Rho GTPases signaling pathway within 2 h were examined. The results indicated that the inhibition of FAK significantly decreased the migration ability of VECs and human hepatoblastoma cells in a dose-dependent manner. Inhibition of FAK promoted cell detachment by decreasing the expression of focal adhesion components, and blocked cell motility by reducing the level of Rho GTPases. However, the expression of crucial proteins involved in integrin-induced signaling in two cell lines exhibited a time-dependent difference with increased duration of FAK inhibitor treatment, suggesting different mechanisms of FAK-mediated cell migration behavior. These results suggest that the mechanism underlying FAK-mediated adhesion and migration behavior differs among various cells, which is expected to provide evidence for future FAK therapy targeted against tumor angiogenesis.

  20. Systemic focal epileptogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Remler, M.P.; Marcussen, W.H.

    1986-01-01

    Rats that receive radiation to 0.25 cc of one cerebral hemisphere are clinically and electroencephalographically normal until there is a breakdown of the blood-brain barrier (BBB) at 3 to 6 months postradiation. This BBB lesion can be detected by transient focal seizure activity produced by the BBB-excluded systemic convulsant bicuculline methiodide. In two rats the seizure activity induced by this one injection was self-sustaining. In seven of 15 other rats tested, the subsequent administration of repeated 2 mg/kg injections created a chronic focus that continued to spike with great frequency for 3 weeks or more without further administration of any convulsant. In three of eight other rats, implanted minipumps delivering 180 micrograms/h of bicuculline methiodide produced self-sustaining epileptic activity.

  1. Propentofylline treatment on open field behavior in rats with focal ethidium bromide-induced demyelination in the ventral surface of the brainstem.

    Science.gov (United States)

    Martins-Júnior, J L; Bernardi, M M; Bondan, E F

    2016-03-01

    Propentofylline (PPF) is a xanthine derivative with pharmacological effects that are distinct from those of classic methylxanthines. It depresses the activation of microglial cells and astrocytes, which is associated with neuronal damage during neural inflammation and hypoxia. Our previous studies showed that PPF improved remyelination following gliotoxic lesions that were induced by ethidium bromide (EB). In the present study, the long-term effects of PPF on open field behavior in rats with EB-induced focal demyelination were examined. The effects of PPF were first evaluated in naive rats that were not subjected to EB lesions. Behavior in the beam walking test was also evaluated during chronic PPF treatment because impairments in motor coordination can interfere with behavior in the open field. The results showed that PPF treatment in unlesioned rats decreased general activity and caused motor impairment in the beam walking test. Gliotoxic EB injections increased general activity in rats that were treated with PPF compared with rats that received saline solution. Motor incoordination was also attenuated in PPF-treated rats. These results indicate that PPF reversed the effects of EB lesions on behavior in the open field and beam walking test. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Hemorrhagic Shock-Induced Vascular Hyporeactivity in the Rat: Relationship to Gene Expression of Nitric Oxide Synthase, Endothelin-1, and Select Cytokines in Corresponding Organs

    Science.gov (United States)

    2005-01-01

    the Selected Genes Sense Antisense Product length (bp) G3PDH 5=-TCCTGCACCACCAACTGCTTAG-3= 5=-TGCTTCACCACCTTCTTGATGTC-3= 341 iNOS 5...GAPDH, as a housekeeping gene, was not affected significantly by the hemorrhage protocol. The results showed that mRNA levels of all enzymes and

  3. Effect of acupuncture on the genetic expression of myocardial endothelin-1 and atrial natriuretic peptide in rats with stress-induced prehypertension

    Directory of Open Access Journals (Sweden)

    Wenrui Jia

    2017-01-01

    Conclusion: Acupuncture may lower blood pressure and downregulate the genetic expression of myocardial ET-1 and ANP in SIPH rats, suggesting a protective effect of acupuncture against myocardial damage.

  4. Curcumin-loaded nanoparticles ameliorate glial activation and improve myelin repair in lyolecithin-induced focal demyelination model of rat corpus callosum.

    Science.gov (United States)

    Naeimi, Reza; Safarpour, Fatemeh; Hashemian, Mona; Tashakorian, Hamed; Ahmadian, Seyed Raheleh; Ashrafpour, Manouchehr; Ghasemi-Kasman, Maryam

    2018-05-01

    Curcumin has been introduced as effective anti-inflammatory agent in treatment of several inflammatory disorders. Despite the wide range pharmacological activities, clinical application of curcumin is restricted mainly due to the low water solubility of this substance. More recently, we could remarkably improve the aqueous solubility of curcumin by its encapsulation in chitosan-alginate-sodium tripolyphosphate nanoparticles (CS-ALG-STPP NPs). In this study, the anti-inflammatory and myelin protective effects of curcumin-loaded NPs were evaluated in lysolecithin (LPC)-induced focal demyelination model. Pharmacokinetic of curcumin was assessed using high performance liquid chromatography (HPLC). Local demyelination was induced by injection of LPC into corpus callosum of rats. Animals were pre-treated with intraperitoneal (i.p.) injections of curcumin or curcumin-loaded NPs at dose of 12.5 mg/kg, 10 days prior to LPC injection and the injections were continued for 7 or 14 days post lesion. Hematoxylin and eosin (H&E) staining and immunostaining against activated glial cells including astrocytes and microglia were carried out for assessment of inflammation level in lesion site. Myelin specific staining was performed to evaluate the effect of curcumin-loaded NPs on myelination of LPC receiving animals. HPLC results showed the higher plasma concentration of curcumin after administration of NPs. Histological evaluation demonstrated that, the extent of demyelination areas was reduced in animals under treatment of curcumin-loaded NPs. Furthermore, treatment with curcumin-loaded NPs effectively attenuated glial activation and inflammation in LPC-induced demyelination model compared to curcumin receiving animals. Overall; these findings indicate that treatment with curcumin-loaded NPs preserve myelinated axons through amelioration of glial activation and inflammation in demyelination context. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Protective effect of glycyrrhizin, a direct HMGB1 inhibitor, on focal cerebral ischemia/reperfusion-induced inflammation, oxidative stress, and apoptosis in rats.

    Directory of Open Access Journals (Sweden)

    Gu Gong

    Full Text Available AIM: Glycyrrhizin (GL has been reported to protect against ischemia and reperfusion (I/R-induced injury by inhibiting the cytokine activity of high mobility group box 1 (HMGB1. In the present study, the protective effects of GL against I/R injury, as well as the related molecular mechanisms, were investigated in rat brains. METHODS: Focal cerebral I/R injury was induced by intraluminal filamentous occlusion of the middle cerebral artery (MCA in Male Sprague-Dawley rats. GL alone or GL and rHMGB1 were administered intravenously at the time of reperfusion. Serum levels of HMGB1 and inflammatory mediators were quantified via enzyme-linked immunosorbent assay (ELISA. Histopathological examination, immunofluorescence, RT-PCR and western blotting analyses were performed to investigate the protective and anti-apoptotic effects and related molecular mechanisms of GL against I/R injury in rat brains. RESULTS: Pre-treatment with GL significantly reduced infarct volume and improved the accompanying neurological deficits in locomotor function. The release of HMGB1 from the cerebral cortex into the serum was inhibited by GL administration. Moreover, pre-treatment with GL alleviated apoptotic injury resulting from cerebral I/R through the inhibition of cytochrome C release and caspase 3 activity. The expression levels of inflammation- and oxidative stress-related molecules including TNF-α, iNOS, IL-1β, and IL-6, which were over-expressed in I/R, were decreased by GL. P38 and P-JNK signalling were involved in this process. All of the protective effects of GL could be reversed by rHMGB1 administration. CONCLUSIONS: GL has a protective effect on ischemia-reperfusion injury in rat brains through the inhibition of inflammation, oxidative stress and apoptotic injury by antagonising the cytokine activity of HMGB1.

  6. Focal dermal hypoplasia without focal dermal hypoplasia

    NARCIS (Netherlands)

    Contreras-Capetillo, Silvina N.; Lombardi, Maria Paola; Pinto-Escalante, Doris; Hennekam, Raoul C.

    2014-01-01

    Focal dermal hypoplasia (FDH; Goltz-Gorlin syndrome) is an X-linked dominant disorder affecting mainly tissues of ectodermal and mesodermal origin. The phenotype is characterized by hypoplastic linear skin lesions, eye malformations, hair and teeth anomalies, and multiple limbs malformations. The

  7. Focal lesions in the central nervous system

    International Nuclear Information System (INIS)

    Fabrikant, J.I.; Budinger, T.F.; Tobias, C.A.; Born, J.L.

    1980-01-01

    This report reviews the animal and human studies currently in progress at LBL with heavy-ion beams to induce focal lesions in the central nervous system, and discusses the potential future prospects of fundamental and applied brain research with heavy-ion beams. Methods are being developed for producing discrete focal lesions in the central nervous system using the Bragg ionization peak to investigate nerve pathways and neuroendocrine responses, and for treating pathological disorders of the brain

  8. Focal retinal phlebitis.

    Science.gov (United States)

    Hoang, Quan V; Freund, K Bailey; Klancnik, James M; Sorenson, John A; Cunningham, Emmett T; Yannuzzi, Lawrence A

    2012-01-01

    To report three cases of solitary, focal retinal phlebitis. An observational case series. Three eyes in three patients were noted to have unilateral decreased vision, macular edema, and a focal retinal phlebitis, which was not at an arteriovenous crossing. All three patients developed a branch retinal vein occlusion at the site of inflammation. These patients had no other evidence of intraocular inflammation, including vitritis, retinitis, retinal vasculitis, or choroiditis, nor was there any systemic disorder associated with inflammation, infection, or coagulation identified. Focal retinal phlebitis appears to be an uncommon and unique entity that produces macular edema and ultimately branch retinal vein occlusion. In our patients, the focal phlebitis and venous occlusion did not occur at an arteriovenous crossing, which is the typical site for branch retinal venous occlusive disease. This suggests that our cases represent a distinct clinical entity, which starts with a focal abnormality in the wall of a retinal venule, resulting in surrounding exudation and, ultimately, ends with branch retinal vein occlusion.

  9. Immediate and Catastrophic Antibody-Mediated Rejection in a Lung Transplant Recipient With Anti-Angiotensin II Receptor Type 1 and Anti-Endothelin-1 Receptor Type A Antibodies.

    Science.gov (United States)

    Cozzi, E; Calabrese, F; Schiavon, M; Feltracco, P; Seveso, M; Carollo, C; Loy, M; Cardillo, M; Rea, F

    2017-02-01

    Preexisting donor-specific anti-HLA antibodies (DSAs) have been associated with reduced survival of lung allografts. However, antibodies with specificities other than HLA may have a detrimental role on the lung transplant outcome. A young man with cystic fibrosis underwent lung transplantation with organs from a suitable deceased donor. At the time of transplantation, there were no anti-HLA DSAs. During surgery, the patient developed a severe and intractable pulmonary hypertension associated with right ventriular dysfunction, which required arteriovenous extracorporeal membrane oxygenation. After a brief period of clinical improvement, a rapid deterioration in hemodynamics led to the patient's death on postoperative day 5. Postmortem studies showed that lung specimens taken at the end of surgery were compatible with antibody-mediated rejection (AMR), while terminal samples evidenced diffuse capillaritis, blood extravasation, edema, and microthrombi, with foci of acute cellular rejection (A3). Immunological investigations demonstrated the presence of preexisting antibodies against the endothelin-1 receptor type A (ET A R) and the angiotensin II receptor type 1 (AT 1 R), two of the most potent vasoconstrictors reported to date, whose levels slightly rose after transplantation. These data suggest that preexisting anti-ET A R and anti-AT 1 R antibodies may have contributed to the onset of AMR and to the catastrophic clinical course of this patient. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  10. Inhibition of Cathepsins B Induces Neuroprotection Against Secondary Degeneration in Ipsilateral Substantia Nigra After Focal Cortical Infarction in Adult Male Rats

    Directory of Open Access Journals (Sweden)

    Xialin Zuo

    2018-05-01

    Full Text Available Stroke is the leading cause of adult disability in the world. In general, recovery from stroke is incomplete. Accumulating evidences have shown that focal cerebral infarction leads to dynamic trans-neuronal degeneration in non-ischemic remote brain regions, with the disruption of connections to synapsed neurons sustaining ischemic insults. Previously, we had reported that the ipsilateral striatum, thalamus degenerated in succession after permanent distal branch of middle cerebral artery occlusion (dMCAO in Sprague-Dawley (SD rats and cathepsin (Cath B was activated before these relay degeneration. Here, we investigate the role of CathB in the secondary degeneration of ipsilateral substantia nigra (SN after focal cortical infarction. We further examined whether the inhibition of CathB with L-3-trans-(Propyl-carbamoyloxirane-2-carbonyl-L-isoleucyl-L-proline methyl ester (CA-074Me would attenuate secondary degeneration through enhancing the cortico-striatum-nigral connections and contribute to the neuroprotective effects. Our results demonstrated that secondary degeneration in the ipsilateral SN occurred and CathB was upregulated in the ipsilateral SN after focal cortical infarction. The inhibition of CathB with CA-074Me reduced the neuronal loss and gliosis in the ipsilateral SN. Using biotinylated dextran amine (BDA or pseudorabies virus (PRV 152 as anterograde or retrograde tracer to trace striatum-nigral and cortico-nigral projections pathway, CA-074Me can effectively enhance the cortico-striatum-nigral connections and exert neuroprotection against secondary degeneration in the ipsilateral SN after cortical ischemia. Our study suggests that the lysosomal protease CathB mediates the secondary damage in the ipsilateral SN after dMCAO, thus it can be a promising neuroprotective target for the rehabilitation of stroke patients.

  11. Focal myositis: A review.

    Science.gov (United States)

    Devic, P; Gallay, L; Streichenberger, N; Petiot, P

    2016-11-01

    Amongst the heterogeneous group of inflammatory myopathies, focal myositis stands as a rare and benign dysimmune disease. Although it can be associated with root and/or nerve lesions, traumatic muscle lesions and autoimmune diseases, its triggering factors remain poorly understood. Defined as an isolated inflammatory pseudotumour usually restricted to one skeletal muscle, clinical presentation of focal myositis is that of a rapidly growing solitary mass within a single muscle, usually in the lower limbs. Electromyography shows spontaneous activity associated with a myopathic pattern. MRI reveals a contrast enhanced enlarged muscle appearing hyper-intense on FAT-SAT T2 weighted images. Adjacent structures are spared and there are no calcifications. Serum creatine kinase (CK) levels are usually moderately augmented and biological markers of systemic inflammation are absent in most cases. Pathological histological features include marked variation in fibre size, inflammatory infiltrates mostly composed of T CD4+ lymphocytes and macrophages, degenerating/regenerating fibres and interstitial fibrosis. Differential diagnoses are numerous and include myositis of other origin with focal onset. Steroid treatment should be reserved for patients who present with major pain, nerve lesions, associated autoimmune disease, or elevated C reactive protein or CK. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Interactive HIV-1 Tat and morphine-induced synaptodendritic injury is triggered through focal disruptions in Na⁺ influx, mitochondrial instability, and Ca²⁺ overload.

    Science.gov (United States)

    Fitting, Sylvia; Knapp, Pamela E; Zou, Shiping; Marks, William D; Bowers, M Scott; Akbarali, Hamid I; Hauser, Kurt F

    2014-09-17

    Synaptodendritic injury is thought to underlie HIV-associated neurocognitive disorders and contributes to exaggerated inflammation and cognitive impairment seen in opioid abusers with HIV-1. To examine events triggering combined transactivator of transcription (Tat)- and morphine-induced synaptodendritic injury systematically, striatal neuron imaging studies were conducted in vitro. These studies demonstrated nearly identical pathologic increases in dendritic varicosities as seen in Tat transgenic mice in vivo. Tat caused significant focal increases in intracellular sodium ([Na(+)]i) and calcium ([Ca(2+)]i) in dendrites that were accompanied by the emergence of dendritic varicosities. These effects were largely, but not entirely, attenuated by the NMDA and AMPA receptor antagonists MK-801 and CNQX, respectively. Concurrent morphine treatment accelerated Tat-induced focal varicosities, which were accompanied by localized increases in [Ca(2+)]i and exaggerated instability in mitochondrial inner membrane potential. Importantly, morphine's effects were prevented by the μ-opioid receptor antagonist CTAP and were not observed in neurons cultured from μ-opioid receptor knock-out mice. Combined Tat- and morphine-induced initial losses in ion homeostasis and increases in [Ca(2+)]i were attenuated by the ryanodine receptor inhibitor ryanodine, as well as pyruvate. In summary, Tat induced increases in [Na(+)]i, mitochondrial instability, excessive Ca(2+) influx through glutamatergic receptors, and swelling along dendrites. Morphine, acting via μ-opioid receptors, exacerbates these excitotoxic Tat effects at the same subcellular locations by mobilizing additional [Ca(2+)]i and by further disrupting [Ca(2+)]i homeostasis. We hypothesize that the spatiotemporal relationship of μ-opioid and aberrant AMPA/NMDA glutamate receptor signaling is critical in defining the location and degree to which opiates exacerbate the synaptodendritic injury commonly observed in neuro

  13. Elevated Plasma C-Terminal Endothelin-1 Precursor Fragment Concentrations Are Associated with Less Anxiety in Patients with Cardiovascular Risk Factors. Results from the Observational DIAST-CHF Study.

    Science.gov (United States)

    Meyer, Thomas; Chavanon, Mira-Lynn; Herrrmann-Lingen, Christoph; Roggenthien, Maren; Nolte, Kathleen; Pieske, Burkert; Wachter, Rolf; Edelmann, Frank

    2015-01-01

    The role of endothelin-1 (ET-1) in the neurobiology of anxiety is unknown, therefore, we assessed in the observational multicenter DIAST-CHF study whether the C-terminal ET-1 precursor fragment (CT-proET-1) is linked to anxiety. Plasma concentrations of CT-proET-1 were measured in a total of 1,410 patients presenting with cardiovascular risk factors (mean age 66.91±8.2 years, 49.3% males, mean left ventricular ejection fraction 60.0±8.2%) who had completed the Hospital Anxiety and Depression Scale (HADS) questionnaire. Among the total study cohort (n = 1,410), there were 118 subjects (8.4%) with an HADS anxiety score above the cut-off level of 11 suggestive of clinically relevant anxiety. Plasma CT-proET-1 levels were significantly lower in the group of anxious patients as compared to non-anxious patients (p = 0.013). In regression models adjusted for sex, age, systolic blood pressure, and diameters of left atrium and ventricle, plasma CT-proET-1 was again linked to anxiety (Exp(β) = 0.247, 95%-confidence interval [95%-CI] = 0.067-0.914, p = 0.036). Given the high prevalence of depressive disorders in anxious patients, we additionally included the HADS depression score as an independent variable in the models and found that CT-proET-1 remained a significant predictor of anxiety, independent of comorbid depression (Exp(β) = 0.114, 95%-CI = 0.023-0.566, p = 0.008). Our data from a population-based study in outpatients with cardiovascular risk factors revealed that circulating CT-proET-1 levels are negatively associated with anxiety. Further investigations are required to clarify the putative anxiolytic effect of ET-1 or its precursor molecules in humans and to decipher its mechanistic pathways.

  14. Mexico City normal weight children exposed to high concentrations of ambient PM2.5 show high blood leptin and endothelin-1, vitamin D deficiency, and food reward hormone dysregulation versus low pollution controls. Relevance for obesity and Alzheimer disease.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; D'Angiulli, Amedeo; Rodríguez-Díaz, Joel; Blaurock-Busch, Eleonore; Busch, Yvette; Chao, Chih-kai; Thompson, Charles; Mukherjee, Partha S; Torres-Jardón, Ricardo; Perry, George

    2015-07-01

    Millions of Mexico, US and across the world children are overweight and obese. Exposure to fossil-fuel combustion sources increases the risk for obesity and diabetes, while long-term exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with increased risk of Alzheimer's disease (AD). Mexico City Metropolitan Area children are chronically exposed to PM2.5 and O3 concentrations above the standards and exhibit systemic, brain and intrathecal inflammation, cognitive deficits, and Alzheimer disease neuropathology. We investigated adipokines, food reward hormones, endothelial dysfunction, vitamin D and apolipoprotein E (APOE) relationships in 80 healthy, normal weight 11.1±3.2 year olds matched by age, gender, BMI and SES, low (n: 26) versus high (n:54) PM2.5 exposures. Mexico City children had higher leptin and endothelin-1 (pMexico City APOE 4 versus 3 children had higher glucose (p=0.009). Serum 25-hydroxyvitamin DMexico City children. Leptin is strongly positively associated to PM 2.5 cumulative exposures. Residing in a high PM2.5 and O3 environment is associated with 12h fasting hyperleptinemia, altered appetite-regulating peptides, vitamin D deficiency, and increases in ET-1 in clinically healthy children. These changes could signal the future trajectory of urban children towards the development of insulin resistance, obesity, type II diabetes, premature cardiovascular disease, addiction-like behavior, cognitive impairment and Alzheimer's disease. Increased efforts should be made to decrease pediatric PM2.5 exposures, to deliver health interventions prior to the development of obesity and to identify and mitigate environmental factors influencing obesity and Alzheimer disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Elevated Plasma C-Terminal Endothelin-1 Precursor Fragment Concentrations Are Associated with Less Anxiety in Patients with Cardiovascular Risk Factors. Results from the Observational DIAST-CHF Study.

    Directory of Open Access Journals (Sweden)

    Thomas Meyer

    Full Text Available The role of endothelin-1 (ET-1 in the neurobiology of anxiety is unknown, therefore, we assessed in the observational multicenter DIAST-CHF study whether the C-terminal ET-1 precursor fragment (CT-proET-1 is linked to anxiety.Plasma concentrations of CT-proET-1 were measured in a total of 1,410 patients presenting with cardiovascular risk factors (mean age 66.91±8.2 years, 49.3% males, mean left ventricular ejection fraction 60.0±8.2% who had completed the Hospital Anxiety and Depression Scale (HADS questionnaire.Among the total study cohort (n = 1,410, there were 118 subjects (8.4% with an HADS anxiety score above the cut-off level of 11 suggestive of clinically relevant anxiety. Plasma CT-proET-1 levels were significantly lower in the group of anxious patients as compared to non-anxious patients (p = 0.013. In regression models adjusted for sex, age, systolic blood pressure, and diameters of left atrium and ventricle, plasma CT-proET-1 was again linked to anxiety (Exp(β = 0.247, 95%-confidence interval [95%-CI] = 0.067-0.914, p = 0.036. Given the high prevalence of depressive disorders in anxious patients, we additionally included the HADS depression score as an independent variable in the models and found that CT-proET-1 remained a significant predictor of anxiety, independent of comorbid depression (Exp(β = 0.114, 95%-CI = 0.023-0.566, p = 0.008.Our data from a population-based study in outpatients with cardiovascular risk factors revealed that circulating CT-proET-1 levels are negatively associated with anxiety. Further investigations are required to clarify the putative anxiolytic effect of ET-1 or its precursor molecules in humans and to decipher its mechanistic pathways.

  16. Focal femoral condyle resurfacing.

    LENUS (Irish Health Repository)

    Brennan, S A

    2013-03-01

    Focal femoral inlay resurfacing has been developed for the treatment of full-thickness chondral defects of the knee. This technique involves implanting a defect-sized metallic or ceramic cap that is anchored to the subchondral bone through a screw or pin. The use of these experimental caps has been advocated in middle-aged patients who have failed non-operative methods or biological repair techniques and are deemed unsuitable for conventional arthroplasty because of their age. This paper outlines the implant design, surgical technique and biomechanical principles underlying their use. Outcomes following implantation in both animal and human studies are also reviewed. Cite this article: Bone Joint J 2013;95-B:301-4.

  17. Focal midbrain tumors in children

    NARCIS (Netherlands)

    Vandertop, W. P.; Hoffman, H. J.; Drake, J. M.; Humphreys, R. P.; Rutka, J. T.; Amstrong, D. C.; Becker, L. E.

    1992-01-01

    The clinical and neuroradiological features of focal midbrain tumors in 12 children are described, and the results of their surgical management are presented. Patients with a focal midbrain tumor usually exhibit either symptoms and signs of raised intracranial pressure caused by an obstructive

  18. Chronic Fluoxetine Induces Activity Changes in Recovery From Poststroke Anxiety, Depression, and Cognitive Impairment.

    Science.gov (United States)

    Vahid-Ansari, Faranak; Albert, Paul R

    2018-01-01

    Poststroke depression (PSD) is a common outcome of stroke that limits recovery and is only partially responsive to chronic antidepressant treatment. In order to elucidate changes in the cortical-limbic circuitry associated with PSD and its treatment, we examined a novel mouse model of persistent PSD. Focal endothelin-1-induced ischemia of the left medial prefrontal cortex (mPFC) in male C57BL6 mice resulted in a chronic anxiety and depression phenotype. Here, we show severe cognitive impairment in spatial learning and memory in the stroke mice. The behavioral and cognitive phenotypes were reversed by chronic (4-week) treatment with fluoxetine, alone or with voluntary exercise (free-running wheel), but not by exercise alone. To assess chronic cellular activation, FosB + cells were co-labeled for markers of glutamate/pyramidal (VGluT1-3/CaMKIIα), γ-aminobutyric acid (GAD67), and serotonin (TPH). At 6 weeks poststroke versus sham (or 4 days poststroke), left mPFC stroke induced widespread FosB activation, more on the right (contralesional) than on the left side. Stroke activated glutamate cells of the mPFC, nucleus accumbens, amygdala, hippocampus, and raphe serotonin neurons. Chronic fluoxetine balanced bilateral neuronal activity, reducing total FosB and FosB/CamKII + cells (mPFC, nucleus accumbens), and unlike exercise, increasing FosB/GAD67 + cells (septum, amygdala) or both (hippocampus, raphe). In summary, chronic antidepressant but not exercise mediates recovery in this unilateral ischemic PSD model that is associated with region-specific reversal of stroke-induced pyramidal cell hyperactivity and increase in γ-aminobutyric acidergic activity. Targeted brain stimulation to restore brain activity could provide a rational approach for treating clinical PSD.

  19. VEGF attenuated increase of outward delayed-rectifier potassium currents in hippocampal neurons induced by focal ischemia via PI3-K pathway.

    Science.gov (United States)

    Wu, K W; Yang, P; Li, S S; Liu, C W; Sun, F Y

    2015-07-09

    We recently indicated that the vascular endothelial growth factor (VEGF) protects neurons against hypoxic death via enhancement of tyrosine phosphorylation of Kv1.2, an isoform of the delayed-rectifier potassium channels through activation of the phosphatidylinositol 3-kinase (PI3-K) signaling pathway. The present study investigated whether VEGF could attenuate ischemia-induced increase of the potassium currents in the hippocampal pyramidal neurons of rats after ischemic injury. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) to induce brain ischemia. The whole-cell patch-clamp technique was used to record the potassium currents of hippocampal neurons in brain slices from the ischemically injured brains of the rats 24h after MCAO. We detected that transient MCAO caused a significant increase of voltage-gated potassium currents (Kv) and outward delayed-rectifier potassium currents (IK), but not outward transient potassium currents (IA), in the ipsilateral hippocampus compared with the sham. Moreover, we found that VEGF could acutely, reversibly and voltage-dependently inhibit the ischemia-induced IK increase. This inhibitory effect of VEGF could be completely abolished by wortmannin, an inhibitor of PI3-K. Our data indicate that VEGF attenuates the ischemia-induced increase of IK via activation of the PI3-K signaling pathway. Published by Elsevier Ltd.

  20. Bcl-w, a Radio-resistant Protein, Promotes the Gastric Cancer Cell Migration by inducing the phosphorylation of Focal Adhesion Kinase

    International Nuclear Information System (INIS)

    Bae, In Hwa; Yoon, Sung Hwan; Um, Hong Duck

    2008-01-01

    Gastric cancer is one of the leading malignancies in many countries and lethal for the high incidence of recurrence even after drastic surgical resection. Because local invasion and subsequent metastasis contributes to the failure of anticancer treatments of gastric cancer, a better understanding of the mechanisms involved in tumor invasiveness within the stomach seems to be essential for the control of this disease. Bcl-w is a prosurvival member of the Bcl-2 protein family, and thus protects cells from γ-irradiation. Recent reports suggest that Bcl-w can be upregulated in gastric cancer cells in a manner associated with the infiltrative (diffuse) types of the tumor. An analysis of Bcl-w function consistently revealed that Bcl-w can also promote the migratory and invasive potentials of gastric cancer cells. While it was shown that Bcl-w increases the invasiveness of cancer cells by sequentially inducing PI3K, Akt, SP1, and MMP-2, cellular components involved in Bcl-w-induced cell migration remain to be determined. This was the reason why we undertook the present study, which shows that FAK is a critical mediator of the cell migration induced by Bcl-w

  1. Diagnostic imaging in focal epilepsy

    International Nuclear Information System (INIS)

    Zlatareva, D.

    2013-01-01

    Focal epilepsies account for 60% of all seizure disorders worldwide. In this review the classic and new classification system of epileptic seizures and syndromes as well as genetic forms are discussed. Magnetic resonance (MR) is the technique of choice for diagnostic imaging in focal epilepsy because of its sensitivity and high tissue contrast. The review is focused on the lack of consensus of imaging protocols and reported findings in refractory epilepsy. The most frequently encountered MRI findings in epilepsy are reported and their imaging characteristics are depicted. Diagnosis of hippocampal sclerosis and malformations of cortical development as two major causes of refractory focal epilepsy is described in details. Some promising new techniques as positron emission tomography computed tomography (PET/CT) and MR and PET/CT fusion are briefly discussed. Also the relevance of adequate imaging in focal epilepsy, some practical points in imaging interpretation and differential diagnosis are highlighted. (author)

  2. [Estimation of Time-Dependent microRNA Expression Patterns in Brain Tissue, Leukocytes, and Blood Plasma of Rats under Photochemically Induced Focal Cerebral Ischemia].

    Science.gov (United States)

    Gusar, V A; Timofeeva, A V; Zhanin, I S; Shram, S I; Pinelis, V G

    2017-01-01

    miRNA expression over different time periods (24 and 48 h) using the quantitative RT-PCR and deep sequencing has been evaluated in a model of photochemically induced thrombosis. A combination of two approaches allowed us to determine the miRNA expression patterns caused by ischemia. Nine miRNAs, including let-7f-5p, miR-221-3p, miR-21-5p, miR-30c-5p, miR-30a-3p, miR-223-3p, miR-23a-3p, miR-22-5p, and miR-99a-5p, were differentially expressed in brain tissue and leukocytes of rats 48 h after onset of ischemia. In addition, six miRNAs were differentially expressed in the brain tissue and blood plasma of rats 24 h after exposure, among which miR-145-3p and miR-375-3p were downregulated and miR-19a-3p, miR-92a-3p, miR-188-5p, and miR-532-5p were upregulated. In our opinion, miR-188-5p and miR-532-5p may be considered to be new potential markers of ischemic injury. The level of miRNA expression tended to increase 48 h after the onset of ischemia in brain tissue and leukocytes, which reflects not only the local response in brain tissue due to inflammation, vascular endothelial dysfunction, and disorders of the permeability of the blood-brain barrier, but also the systemic response of the organism to multifactor molecular processes induced by ischemic injury.

  3. Evaluation of cellular viability by quantitative autoradiographic study of myocardial uptake of a fatty acid analogue in isoproterenol-induced focal rat heart necrosis

    International Nuclear Information System (INIS)

    Humbert, T.; Luu-Duc, C.; Comet, M.; Demenge, P.

    1991-01-01

    Previous studies led us to hypothesize that a fatty acid analogue, 15-p-iodophenyl-β-methyl pentadecanoic acid (IMPPA or BMIPP), which is taken up but not quickly metabolized by heart cells, would be a more suitable tracer of cellular viability that 201 Tl. Biodistribution studies of 1- 14 C-IMPPA in conscious, freely moving rats showed that the concentration ratio of radioactivity in the heart with respect to the blood was about 8 for at least 60 min after intravenous administration, permitting its use as a putative tracer in these conscious, freely moving rats. Thereafter, the myocardial uptake of 14 C-IMPPA was studied in isoproterenol-treated rats (daily treatment for 10 days in order to induce cardiac hypertrophy and necrotic foci) with respect to control ones. Comparison of myocardial localizations by quantitative autoradiography of the uptake of 201 Tl and 14 C-IMPPA with that of triphenyltetrazolium chloride (TTC) staining enabled comparative evaluation of nutritional blood flow, localization and uptake of 14 C-IMPPA and necrotic foci size. Distributions of 14 C-IMPPA and 201 Tl in control rats' hearts were homogenous, like TTC staining. In infarcted hearts, areas of decreased 14 C-IMPPA uptake were nearly the same (100%±5%) as those unstained by TTC. These areas were larger than those showing a decrease in thallium uptake (about 70%±5% of the total scar size). Therefore, IMPPA seems to be a more accurate and sensitive indicator of necrosis localization compared with thallium. It may be a useful agent for assessment of myocardial viability by single photon emission tomography (SPET) imaging. (orig.)

  4. Recombinant Tissue Plasminogen Activator Induces Neurological Side Effects Independent on Thrombolysis in Mechanical Animal Models of Focal Cerebral Infarction: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Mei-Xue Dong

    Full Text Available Recombinant tissue plasminogen activator (rtPA is the only effective drug approved by US FDA to treat ischemic stroke, and it contains pleiotropic effects besides thrombolysis. We performed a meta-analysis to clarify effect of tissue plasminogen activator (tPA on cerebral infarction besides its thrombolysis property in mechanical animal stroke.Relevant studies were identified by two reviewers after searching online databases, including Pubmed, Embase, and ScienceDirect, from 1979 to 2016. We identified 6, 65, 17, 12, 16, 12 and 13 comparisons reporting effect of endogenous tPA on infarction volume and effects of rtPA on infarction volume, blood-brain barrier, brain edema, intracerebral hemorrhage, neurological function and mortality rate in all 47 included studies. Standardized mean differences for continuous measures and risk ratio for dichotomous measures were calculated to assess the effects of endogenous tPA and rtPA on cerebral infarction in animals. The quality of included studies was assessed using the Stroke Therapy Academic Industry Roundtable score. Subgroup analysis, meta-regression and sensitivity analysis were performed to explore sources of heterogeneity. Funnel plot, Trim and Fill method and Egger's test were obtained to detect publication bias.We found that both endogenous tPA and rtPA had not enlarged infarction volume, or deteriorated neurological function. However, rtPA would disrupt blood-brain barrier, aggravate brain edema, induce intracerebral hemorrhage and increase mortality rate.This meta-analysis reveals rtPA can lead to neurological side effects besides thrombolysis in mechanical animal stroke, which may account for clinical exacerbation for stroke patients that do not achieve vascular recanalization with rtPA.

  5. Inhibition on Apoptosis Induced by Elevated Hydrostatic Pressure in Retinal Ganglion Cell-5 via Laminin Upregulating β1-integrin/Focal Adhesion Kinase/Protein Kinase B Signaling Pathway.

    Science.gov (United States)

    Li, Yi; Chen, Yan-Ming; Sun, Ming-Ming; Guo, Xiao-Dan; Wang, Ya-Chen; Zhang, Zhong-Zhi

    2016-04-20

    Glaucoma is a progressive optic neuropathy characterized by degeneration of neurons due to loss of retinal ganglion cells (RGCs). High intraocular pressure (HIOP), the main risk factor, causes the optic nerve damage. However, the precise mechanism of HIOP-induced RGC death is not yet completely understood. This study was conducted to determine apoptosis of RGC-5 cells induced by elevated hydrostatic pressures, explore whether laminin is associated with apoptosis under pressure, whether laminin can protect RGCs from apoptosis and affirm the mechanism that regulates the process of RGCs survival. RGC-5 cells were exposed to 0, 20, 40, and 60 mmHg in a pressurized incubator for 6, 12, and 24 h, respectively. The effect of elevated hydrostatic pressure on RGC-5 cells was measured by Annexin V-fluorescein isothiocyanate/propidium iodide staining, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and Western blotting of cleaved caspase-3 protein. Location and expression of laminin were detected by immunofluorescence. The expression of β1-integrin, phosphorylation of focal adhesion kinase (FAK) and protein kinase B (PKB, or AKT) were investigated with real-time polymerase chain reaction and Western blotting analysis. Elevated hydrostatic pressure induced apoptosis in cultured RGC-5 cells. Pressure with 40 mmHg for 24 h induced a maximum apoptosis. Laminin was declined in RGC-5 cells after exposing to 40 mmHg for 24 h. After pretreating with laminin, RGC-5 cells survived from elevated pressure. Furthermore, β1-integrin and phosphorylation of FAK and AKT were increased compared to 40 mmHg group. The data show apoptosis tendency of RGC-5 cells with elevated hydrostatic pressure. Laminin can protect RGC-5 cells against high pressure via β1-integrin/FAK/AKT signaling pathway. These results suggest that the decreased laminin of RGC-5 cells might be responsible for apoptosis induced by elevated hydrostatic pressure, and laminin or activating β1-integrin

  6. Lesion Size Is Exacerbated in Hypoxic Rats Whereas Hypoxia-Inducible Factor-1 Alpha and Vascular Endothelial Growth Factor Increase in Injured Normoxic Rats: A Prospective Cohort Study of Secondary Hypoxia in Focal Traumatic Brain Injury.

    Science.gov (United States)

    Thelin, Eric Peter; Frostell, Arvid; Mulder, Jan; Mitsios, Nicholas; Damberg, Peter; Aski, Sahar Nikkhou; Risling, Mårten; Svensson, Mikael; Morganti-Kossmann, Maria Cristina; Bellander, Bo-Michael

    2016-01-01

    Hypoxia following traumatic brain injury (TBI) is a severe insult shown to exacerbate the pathophysiology, resulting in worse outcome. The aim of this study was to investigate the effects of a hypoxic insult in a focal TBI model by monitoring brain edema, lesion volume, serum biomarker levels, immune cell infiltration, as well as the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Female Sprague-Dawley rats (n = 73, including sham and naive) were used. The rats were intubated and mechanically ventilated. A controlled cortical impact device created a 3-mm deep lesion in the right parietal hemisphere. Post-injury, rats inhaled either normoxic (22% O2) or hypoxic (11% O2) mixtures for 30 min. The rats were sacrificed at 1, 3, 7, 14, and 28 days post-injury. Serum was collected for S100B measurements using ELISA. Ex vivo magnetic resonance imaging (MRI) was performed to determine lesion size and edema volume. Immunofluorescence was employed to analyze neuronal death, changes in cerebral macrophage- and neutrophil infiltration, microglia proliferation, apoptosis, complement activation (C5b9), IgG extravasation, HIF-1α, and VEGF. The hypoxic group had significantly increased blood levels of lactate and decreased pO2 (p hypoxic animals (p hypoxic group at 1 day after trauma (p = 0.0868). No differences were observed between the groups in cytotoxic and vascular edema, IgG extravasation, neutrophils and macrophage aggregation, microglia proliferation, or C5b-9 expression. Hypoxia following focal TBI exacerbated the lesion size and neuronal loss. Moreover, there was a tendency to higher levels of S100B in the hypoxic group early after injury, indicating a potential validity as a biomarker of injury severity. In the normoxic group, the expression of HIF-1α and VEGF was found elevated, possibly indicative of neuro-protective responses occurring in this less severely injured group. Further studies are

  7. Continuously variable focal length lens

    Science.gov (United States)

    Adams, Bernhard W; Chollet, Matthieu C

    2013-12-17

    A material preferably in crystal form having a low atomic number such as beryllium (Z=4) provides for the focusing of x-rays in a continuously variable manner. The material is provided with plural spaced curvilinear, optically matched slots and/or recesses through which an x-ray beam is directed. The focal length of the material may be decreased or increased by increasing or decreasing, respectively, the number of slots (or recesses) through which the x-ray beam is directed, while fine tuning of the focal length is accomplished by rotation of the material so as to change the path length of the x-ray beam through the aligned cylindrical slows. X-ray analysis of a fixed point in a solid material may be performed by scanning the energy of the x-ray beam while rotating the material to maintain the beam's focal point at a fixed point in the specimen undergoing analysis.

  8. Testing of focal plane arrays

    International Nuclear Information System (INIS)

    Merriam, J.D.

    1988-01-01

    Problems associated with the testing of focal plane arrays are briefly examined with reference to the instrumentation and measurement procedures. In particular, the approach and instrumentation used as the Naval Ocean Systems Center is presented. Most of the measurements are made with flooded illumination on the focal plane array. The array is treated as an ensemble of individual pixels, data being taken on each pixel and array averages and standard deviations computed for the entire array. Data maps are generated, showing the pixel data in the proper spatial position on the array and the array statistics

  9. Focal therapy in prostate cancer

    NARCIS (Netherlands)

    van den Bos, W.

    2016-01-01

    Interesting developments took place in the treatment of prostate cancer including focal therapy for less aggressive organ-confined prostate cancer. Fortunately, curative treatment is often still an option for patients suffering from the lower staged tumors. In carefully selected patients, the

  10. Gallbladder adenoma with focal adenocarcinoma.

    Science.gov (United States)

    Ciurea, S; Matei, E; Petrisor, P; Luca, L; Boros, Mirela; Herlea, V; Popescu, I

    2008-01-01

    The majority of polypoid lesions of the gallbladder are cholesterolosis pseudopolyps. True neoplastic GB polyps are represented mainly by adenomas. The case of a 52-year old male patient with an adenomatous polyp of the GB with focal adenocarcinoma is presented.

  11. Charging as a Focal Practice

    DEFF Research Database (Denmark)

    Bødker, Mads

    This position paper reflects on Borgmann’s notion of ‘focal things’ and its applicability in the discourse about interaction with technologies in nature. Using the example of a combined cooking burner and thermoelectric 5W smartphone charger (a BioLite cook stove), this position paper gives...

  12. Focal shift and faculae dimension of focused flat beam propagating in turbulent atmosphere

    International Nuclear Information System (INIS)

    Zhang Jianzhu; Li Youkuan; Zhang Feizhou; An Jianzhu

    2011-01-01

    Through theoretic analysis and numerical simulation,the focal shift of a focused flat beam propagating in turbulent atmosphere is studied. When a focused flat beam propagates in turbulent atmosphere, the effect of turbulence will induce the focal spot to move toward the transmitter. The turbulence is stronger and the diameter of transmitter is smaller, the measure of focal shift is larger. When adjusting the focus of transmitter and letting the focal spot of beam locate on detector, the laser intensity received by detector is not the strongest. The laser intensity will be the strongest if the focus of transmitter equals to the distance from transmitter to detector. (authors)

  13. Serial neuroradiological studies in focal cerebritis

    International Nuclear Information System (INIS)

    Hatta, S.; Mochizuki, H.; Kuru, Y.; Miwa, H.; Kondo, T.; Mori, H.; Mizuno, Y.

    1994-01-01

    We report serial neuroradiological studies in a patient with focal cerebritis in the head of the left caudate nucleus. On the day after the onset of symptoms, CT showed an ill-defined low density lesion. The lack of contrast enhancement appeared to be the most important finding for differentiating focal cerebritis from an encapsulated brain abscess or a tumour. MRI two days later revealed the centre of the lesion to be of slightly low intensity on T1-weighted inversion recovery (IR) images and very low intensity on T2-weighted spin echo images, which appeared to correspond to the early cerebritis stage of experimentally induced cerebritis and brain abscess. Ten days after the onset of symptoms, CT revealed a thin ring of enhancement in the head of the caudate nucleus, and a similar small ring was seen in the hypothalamus 16 days after the onset, corresponding to the late cerebritis stage. MRI nine days later revealed ill-defined high signal lesions within the involved area on the T1-weighted IR images. To our knowledge, this is the first published MRI documentation of the early cerebritis stage developing into an encapsulated brain abscess. The mechanisms underlying of these radiographic changes are discussed. (orig.)

  14. [Focal myositis: An unknown disease].

    Science.gov (United States)

    Gallay, L; Streichenberger, N; Benveniste, O; Allenbach, Y

    2017-10-01

    Focal myositis are inflammatory muscle diseases of unknown origin. At the opposite from the other idiopathic inflammatory myopathies, they are restricted to a single muscle or to a muscle group. They are not associated with extramuscular manifestations, and they have a good prognosis without any treatment. They are characterized by a localized swelling affecting mostly lower limbs. The pseudo-tumor can be painful, but is not associated with a muscle weakness. Creatine kinase level is normal. Muscle MRI shows an inflammation restricted to a muscle or a muscle group. Muscle biopsy and pathological analysis remain necessary for the diagnosis, showing inflammatory infiltrates composed by macrophages and lymphocytes without any specific distribution within the muscle. Focal overexpression of HLA-1 by the muscle fibers is frequently observed. The muscle biopsy permits to rule out differential diagnosis such a malignancy (sarcoma). Spontaneous remission occurs within weeks or months after the first symptoms, relapse is unusual. Copyright © 2017. Published by Elsevier SAS.

  15. Focal cortical dysplasia – review

    International Nuclear Information System (INIS)

    Kabat, Joanna; Król, Przemysław

    2012-01-01

    Focal cortical dysplasia is a malformation of cortical development, which is the most common cause of medically refractory epilepsy in the pediatric population and the second/third most common etiology of medically intractable seizures in adults. Both genetic and acquired factors are involved in the pathogenesis of cortical dysplasia. Numerous classifications of the complex structural abnormalities of focal cortical dysplasia have been proposed – from Taylor et al. in 1971 to the last modification of Palmini classification made by Blumcke in 2011. In general, three types of cortical dysplasia are recognized. Type I focal cortical dysplasia with mild symptomatic expression and late onset, is more often seen in adults, with changes present in the temporal lobe. Clinical symptoms are more severe in type II of cortical dysplasia usually seen in children. In this type, more extensive changes occur outside the temporal lobe with predilection for the frontal lobes. New type III is one of the above dysplasias with associated another principal lesion as hippocampal sclerosis, tumor, vascular malformation or acquired pathology during early life. Brain MRI imaging shows abnormalities in the majority of type II dysplasias and in only some of type I cortical dysplasias. The most common findings on MRI imaging include: focal cortical thickening or thinning, areas of focal brain atrophy, blurring of the gray-white junction, increased signal on T2- and FLAIR-weighted images in the gray and subcortical white matter often tapering toward the ventricle. On the basis of the MRI findings, it is possible to differentiate between type I and type II cortical dysplasia. A complete resection of the epileptogenic zone is required for seizure-free life. MRI imaging is very helpful to identify those patients who are likely to benefit from surgical treatment in a group of patients with drug-resistant epilepsy. However, in type I cortical dysplasia, MR imaging is often normal, and also in both

  16. Systems considerations in mosaic focal planes

    Science.gov (United States)

    White, K. P., III

    1983-08-01

    Two key reasons for pursuing the development of mosaic focal planes are reviewed and it is shown that rapid frame repetition rate is the only requirement that can be solved no other way than through mosaic focal planes. With the view that spaceborne mosaic focal plane sensors are necessarily 'smart sensors' requiring a lot of onboard processing just to function, it is pointed out that various artificial intelligence techniques may be the most appropriate to incorporate in the data processing. Finally, a novel mosaic focal plane design is proposed, termed a virtual mosaic focal plane, in response to other system constraints.

  17. TRIM15 is a focal adhesion protein that regulates focal adhesion disassembly

    Science.gov (United States)

    Uchil, Pradeep D.; Pawliczek, Tobias; Reynolds, Tracy D.; Ding, Siyuan; Hinz, Angelika; Munro, James B.; Huang, Fang; Floyd, Robert W.; Yang, Haitao; Hamilton, William L.; Bewersdorf, Joerg; Xiong, Yong; Calderwood, David A.; Mothes, Walther

    2014-01-01

    ABSTRACT Focal adhesions are macromolecular complexes that connect the actin cytoskeleton to the extracellular matrix. Dynamic turnover of focal adhesions is crucial for cell migration. Paxillin is a multi-adaptor protein that plays an important role in regulating focal adhesion dynamics. Here, we identify TRIM15, a member of the tripartite motif protein family, as a paxillin-interacting factor and a component of focal adhesions. TRIM15 localizes to focal contacts in a myosin-II-independent manner by an interaction between its coiled-coil domain and the LD2 motif of paxillin. Unlike other focal adhesion proteins, TRIM15 is a stable focal adhesion component with restricted mobility due to its ability to form oligomers. TRIM15-depleted cells display impaired cell migration and reduced focal adhesion disassembly rates, in addition to enlarged focal adhesions. Thus, our studies demonstrate a cellular function for TRIM15 as a regulatory component of focal adhesion turnover and cell migration. PMID:25015296

  18. Heterogeneity of Focal Adhesions and Focal Contacts in Motile Fibroblasts.

    Science.gov (United States)

    Gladkikh, Aleena; Kovaleva, Anastasia; Tvorogova, Anna; Vorobjev, Ivan A

    2018-01-01

    Cell-extracellular matrix (ECM) adhesion is an important property of virtually all cells in multicellular organisms. Cell-ECM adhesion studies, therefore, are very significant both for biology and medicine. Over the last three decades, biomedical studies resulted in a tremendous advance in our understanding of the molecular basis and functions of cell-ECM adhesion. Based on morphological and molecular criteria, several different types of model cell-ECM adhesion structures including focal adhesions, focal complexes, fibrillar adhesions, podosomes, and three-dimensional matrix adhesions have been described. All the subcellular structures that mediate cell-ECM adhesion are quite heterogeneous, often varying in size, shape, distribution, dynamics, and, to a certain extent, molecular constituents. The morphological "plasticity" of cell-ECM adhesion perhaps reflects the needs of cells to sense, adapt, and respond to a variety of extracellular environments. In addition, cell type (e.g., differentiation status, oncogenic transformation, etc.) often exerts marked influence on the structure of cell-ECM adhesions. Although molecular, genetic, biochemical, and structural studies provide important maps or "snapshots" of cell-ECM adhesions, the area of research that is equally valuable is to study the heterogeneity of FA subpopulations within cells. Recently time-lapse observations on the FA dynamics become feasible, and behavior of individual FA gives additional information on cell-ECM interactions. Here we describe a robust method of labeling of FA using plasmids with fluorescent markers for paxillin and vinculin and quantifying the morphological and dynamical parameters of FA.

  19. Focal nodular hyperplasia: imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Kehagias, D.; Moulopoulos, L.; Antoniou, A.; Hatziioannou, A.; Smyrniotis, V.; Trakadas, S.; Lahanis, S.; Vlahos, L. [Dept. of Radiology, University of Athens (Greece)

    2001-02-01

    Focal nodular hyperplasia is an uncommon benign hepatic tumor that continues to pose diagnostic dilemmas. Imaging techniques are of great value in diagnosis of this tumor. In this article we present the US, CT, MR imaging, scintigraphy, and angiography findings. The demonstration of a central vascular scar is very helpful. Although the radiologic features may be diagnostic, many atypical cases must be differentiated from other benign or malignant hepatic tumors. In these cases excisional biopsy and histopathologic examination are necessary to determine a definite diagnosis. (orig.)

  20. Focal nodular hyperplasia: imaging findings

    International Nuclear Information System (INIS)

    Kehagias, D.; Moulopoulos, L.; Antoniou, A.; Hatziioannou, A.; Smyrniotis, V.; Trakadas, S.; Lahanis, S.; Vlahos, L.

    2001-01-01

    Focal nodular hyperplasia is an uncommon benign hepatic tumor that continues to pose diagnostic dilemmas. Imaging techniques are of great value in diagnosis of this tumor. In this article we present the US, CT, MR imaging, scintigraphy, and angiography findings. The demonstration of a central vascular scar is very helpful. Although the radiologic features may be diagnostic, many atypical cases must be differentiated from other benign or malignant hepatic tumors. In these cases excisional biopsy and histopathologic examination are necessary to determine a definite diagnosis. (orig.)

  1. SNAP Satellite Focal Plane Development

    International Nuclear Information System (INIS)

    Bebek, C.; Akerlof, C.; Aldering, G.; Amanullah, R.; Astier, P.; Baltay, C.; Barrelet, E.; Basa, S.; Bercovitz, J.; Bergstrom, L.; Berstein, G.P.; Bester, M.; Bohlin, R.; Bonissent, A.; Bower, C.; Campbell, M.; Carithers, W.; Commins, E.; Day, C.; Deustua, S.; DiGennaro, R.; Ealet, A.; Ellis, R.; Emmett, W.; Eriksson, M.; Fouchez, D.; Fruchter, A.; Genat, J-F.; Goldhaber, G.; Goobar, A.; Groom, D.; Heetderks, H.; Holland, S.; Huterer, D.; Johnson, W.; Kadel, R.; Karcher, A.; Kim, A.; Kolbe, W.; Lafever, R.; Lamoureaux, J.; Lampton, M.; Lefevre, O.; Levi, M.; Levin, D.; Linder, E.; Loken, S.; Malina, R.; Mazure, A.; McKay, T.; McKee, S.; Miquel, R.; Morgan, N.; Mortsell, E.; Mostek, N.; Mufson, S.; Musser, J.; Roe, N.; Nugent, P.; Oluseyi, H.; Pain, R.; Palaio, N.; Pankow, D.; Perlmutter, S.; Prieto, E.; Rabinowitz, D.; Refregier, A.; Rhodes, J.; Schubnell, M.; Sholl, M.; Smadja, G.; Smith, R.; Smoot, G.; Snyder, J.; Spadafora, A.; Szymkowiak, A.; Tarle, G.; Taylor, K.; Tilquin, A.; Tomasch, A.; Vincent, D.; von der Lippe, H.; Walder, J-P.; Wang, G.

    2003-01-01

    The proposed SuperNova/Acceleration Probe (SNAP) mission will have a two-meter class telescope delivering diffraction-limited images to an instrumented 0.7 square degree field in the visible and near-infrared wavelength regime. The requirements for the instrument suite and the present configuration of the focal plane concept are presented. A two year R and D phase, largely supported by the Department of Energy, is just beginning. We describe the development activities that are taking place to advance our preparedness for mission proposal in the areas of detectors and electronics

  2. MRI of focal cortical dysplasia

    International Nuclear Information System (INIS)

    Lee, B.C.P.; Hatfield, G.A.; Bourgeois, B.; Park, T.S.

    1998-01-01

    We studied nine cases of focal cortical dysplasia (FCD) by MRI, with surface-rendered 3D reconstructions. One case was also examined using single-voxel proton MR spectroscopy (MRS). The histological features were reviewed and correlated with the MRI findings. The gyri affected by FCD were enlarged and the signal of the cortex was slightly increased on T1-weighted images. The gray-white junction was indistinct. Signal from the subcortical white matter was decreased on T1- and increased on T2-weighted images in most cases. Contrast enhancement was seen in two cases. Proton MRS showed a spectrum identical to that of normal brain. (orig.) (orig.)

  3. Pathogenesis of Focal Segmental Glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Beom Jin Lim

    2016-11-01

    Full Text Available Focal segmental glomerulosclerosis (FSGS is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix. FSGS is classified as collapsing, tip, cellular, perihilar and not otherwise specified variants according to the location and character of the sclerotic lesion. Primary or idiopathic FSGS is considered to be related to podocyte injury, and the pathogenesis of podocyte injury has been actively investigated. Several circulating factors affecting podocyte permeability barrier have been proposed, but not proven to cause FSGS. FSGS may also be caused by genetic alterations. These genes are mainly those regulating slit diaphragm structure, actin cytoskeleton of podocytes, and foot process structure. The mode of inheritance and age of onset are different according to the gene involved. Recently, the role of parietal epithelial cells (PECs has been highlighted. Podocytes and PECs have common mesenchymal progenitors, therefore, PECs could be a source of podocyte repopulation after podocyte injury. Activated PECs migrate along adhesion to the glomerular tuft and may also contribute to the progression of sclerosis. Markers of activated PECs, including CD44, could be used to distinguish FSGS from minimal change disease. The pathogenesis of FSGS is very complex; however, understanding basic mechanisms of podocyte injury is important not only for basic research, but also for daily diagnostic pathology practice.

  4. Focal cryotherapy: step by step technique description

    Directory of Open Access Journals (Sweden)

    Cristina Redondo

    Full Text Available ABSTRACT Introduction and objective: Focal cryotherapy emerged as an efficient option to treat favorable and localized prostate cancer (PCa. The purpose of this video is to describe the procedure step by step. Materials and methods: We present the case of a 68 year-old man with localized PCa in the anterior aspect of the prostate. Results: The procedure is performed under general anesthesia, with the patient in lithotomy position. Briefly, the equipment utilized includes the cryotherapy console coupled with an ultrasound system, argon and helium gas bottles, cryoprobes, temperature probes and an urethral warming catheter. The procedure starts with a real-time trans-rectal prostate ultrasound, which is used to outline the prostate, the urethra and the rectal wall. The cryoprobes are pretested and placed in to the prostate through the perineum, following a grid template, along with the temperature sensors under ultrasound guidance. A cystoscopy confirms the right positioning of the needles and the urethral warming catheter is installed. Thereafter, the freeze sequence with argon gas is started, achieving extremely low temperatures (-40°C to induce tumor cell lysis. Sequentially, the thawing cycle is performed using helium gas. This process is repeated one time. Results among several series showed a biochemical disease-free survival between 71-93% at 9-70 month- follow-up, incontinence rates between 0-3.6% and erectile dysfunction between 0-42% (1–5. Conclusions: Focal cryotherapy is a feasible procedure to treat anterior PCa that may offer minimal morbidity, allowing good cancer control and better functional outcomes when compared to whole-gland treatment.

  5. RTG diagnostics of dental focal infection

    International Nuclear Information System (INIS)

    Petrasova, A.; Ondrasovicova, J.; Cecctkova, A.

    2008-01-01

    The theory of focal infection has always been and still is a controversial issue for many dentists and scientists. Even though the focal infection does not occupy the first place in modern medicine, its understanding is imperative. The authors summarized the knowledge about dental focal infection and its relationship to systemic the diseases of the whole body in their publication and they also focused on the radiodiagnostics of this disease. (authors)

  6. Periodontitis in patients with focal tuberculosis

    Directory of Open Access Journals (Sweden)

    Alexandrova Е.А.

    2010-12-01

    Full Text Available The research goal is to investigate the mechanisms of formation and peculiarities of periodontitis in patients with focal tuberculosis. Patients with periodontitis and focal tuberculosis are proved to develop local inflammatory reaction with increased infection and activation of proinflammatory cytokines in parodontal pockets fluid. The main risk factor of frequent and durable recurrence of parodontal pathology in case of focal tuberculosis was the development of pathologic process as a cause of disbalance of lipid peroxidation and antioxidant system, endotoxicosis syndrome

  7. Flux dynamics in ultrasensitive superconducting focal planes

    Data.gov (United States)

    National Aeronautics and Space Administration — The performance of superconducting focal planes will drive the achievable specifications of ultrasensitive instruments for NASA astrophysics missions, yet they have...

  8. Game Movement as Enactive Focalization

    Directory of Open Access Journals (Sweden)

    Yotam Shibolet

    2018-01-01

    Full Text Available This paper integrates thought on game narrative and embodied cognition, in order to consider the significance of movement to the embodied narrative experience of games. If games are a mode of ‘environmental storytelling’, determining the player’s mobile situatedness within the gamespace is of crucial importance. The metaphor of game design as narrative architecture should be expanded to include te the design of movement dynamics, alongside geographical gamespace. I suggest a theoretical infrastructure that aims to enable further analysis of movement design’s role in this scope. The theory of enactive perception asserts that all perception is inherently negotiated through embodied understanding of moving within environment. According to this model, by giving meaning to perception, movement is also directly related to the structure of consciousness and thought. Cognitive definitions of ‘narrative’ that integrate embodiment are applied to argue it can relevantly account for part of thought’s role in enactive perception. Mieke Bal’s concept of focalization (1997 broaches narrative perspective by underscoring the constant “movement of the look”. For enactive perception, such mobility should be understood as inseparable from the movement of the body even when perspective could appear detached from embodiment. Therefore, I offer the supplementary concept of “enactive focalization” – narrative perception as interpreted through the interconnected dynamics or perspectival and physical movement. To exemplify my ideas and the potential of future research in this scope, I discuss the uniquely effective and affective movement dynamic design of Journey. This paper concludes by reflecting on enactive focalization in light of the increased utilization of embodiment in the contemporary digital media landscape.

  9. Systematic study of the focal shift effect in planar plasmonic slit lenses

    International Nuclear Information System (INIS)

    Hu Bin; Wang Qijie; Zhang Ying

    2012-01-01

    In this paper, we systematically studied the focal shift effect in planar plasmonic slit lenses. Through theoretical derivations and numerical simulations, we found that there is a focal length shift between the traditional design model and the finite-difference time-domain simulations. The shift is not only dependent on the Fresnel number (FN) of the lens, like traditional dielectric lenses, determined by the lens width and the designed focal length, but also on the surface plasmon polariton (SPPs) interaction on the lens surfaces, dependent on the slit numbers. We also found that the FN-induced focal shift is predominant when FN 1. An approximated theoretical model is presented to estimate the focal shift of plasmonic slit lens with FN < 1. (paper)

  10. A case of pathological rib fractures: focal osteolysis or osteoporosis?

    Science.gov (United States)

    Vrbanić, T S L; Novak, S; Sestan, B; Tudor, A; Gulan, G

    2008-03-01

    This paper reports on a unique, previously unreported, successful outcome in the case of a patient with focal osteolytic lesions of the ribs as a first sign of osteoporosis. The lesions were detected by chance after acute cough-induced rib fractures were seen on plain chest radiographs. The diagnosis had to be approached as a diagnosis of exclusion since known causes of the osteolytic process had to be eliminated. The authors describe multiple focal osteolytic lesions with rib fractures appearing in a pattern that could be confused with metastases. Laboratory results were normal. Final diagnosis was based on plain radiography, bone scan and bone densitometry. Pharmacomedical treatments for osteoporosis were applied. The patient was observed between the year 2000 and 2005. Five years later radiological and bone scintigraphy revealed resolution of the lesion. We conclude that osteoporosis should be included in the differential diagnosis of asymptomatic focal osteolysis of the ribs with rib fractures as a complication of acute cough. The case suggests that focal osteolytic lesions of the ribs may regress over time and become scintigraphically inactive.

  11. Prenatal sonographic diagnosis of focal musculoskeletal anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jung Kyu; Cho, Jeong Yeon; Lee, Young Ho; Kim, Ei Jeong; Chun, Yi Kyeong [Samsung Cheil Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2002-09-15

    Focal musculoskeletal anomalies are various and may be an isolated finding or may be found in conjunction with numerous associations, including genetic syndromes, Karyotype abnormals, central nervous system anomalies and other general musculoskeletal disorders. Early prenatal diagnosis of these focal musculoskeletal anomalies nor only affects prenatal care and postnatal outcome but also helps in approaching other numerous associated anomalies.

  12. Prenatal sonographic diagnosis of focal musculoskeletal anomalies

    International Nuclear Information System (INIS)

    Ryu, Jung Kyu; Cho, Jeong Yeon; Lee, Young Ho; Kim, Ei Jeong; Chun, Yi Kyeong

    2002-01-01

    Focal musculoskeletal anomalies are various and may be an isolated finding or may be found in conjunction with numerous associations, including genetic syndromes, Karyotype abnormals, central nervous system anomalies and other general musculoskeletal disorders. Early prenatal diagnosis of these focal musculoskeletal anomalies nor only affects prenatal care and postnatal outcome but also helps in approaching other numerous associated anomalies.

  13. Production of high energy, uniform focal profiles with the Nike laser

    Science.gov (United States)

    Lehecka, T.; Lehmberg, R. H.; Deniz, A. V.; Gerber, K. A.; Obenschain, S. P.; Pawley, C. J.; Pronko, M. S.; Sullivan, C. A.

    1995-02-01

    Nike, a KrF laser facility at the Naval Research Laboratory, is designed to produce high intensity, ultra-uniform focal profiles for experiments relating to direct drive inertial confinement fusion. We present measurements of focal profiles through the next-to-last amplifier, a 20 × 20 cm 2 aperture electron beam pumped amplifier capable of producing more than 120 J of output in a 120 ns pulse. Using echelon free induced spatial incoherence beam smoothing this system has produced focal profiles with less than 2% tilt and curvature and less than 2% rms variation from a flat top distribution.

  14. Early vision and focal attention

    Science.gov (United States)

    Julesz, Bela

    1991-07-01

    At the thirty-year anniversary of the introduction of the technique of computer-generated random-dot stereograms and random-dot cinematograms into psychology, the impact of the technique on brain research and on the study of artificial intelligence is reviewed. The main finding-that stereoscopic depth perception (stereopsis), motion perception, and preattentive texture discrimination are basically bottom-up processes, which occur without the help of the top-down processes of cognition and semantic memory-greatly simplifies the study of these processes of early vision and permits the linking of human perception with monkey neurophysiology. Particularly interesting are the unexpected findings that stereopsis (assumed to be local) is a global process, while texture discrimination (assumed to be a global process, governed by statistics) is local, based on some conspicuous local features (textons). It is shown that the top-down process of "shape (depth) from shading" does not affect stereopsis, and some of the models of machine vision are evaluated. The asymmetry effect of human texture discrimination is discussed, together with recent nonlinear spatial filter models and a novel extension of the texton theory that can cope with the asymmetry problem. This didactic review attempts to introduce the physicist to the field of psychobiology and its problems-including metascientific problems of brain research, problems of scientific creativity, the state of artificial intelligence research (including connectionist neural networks) aimed at modeling brain activity, and the fundamental role of focal attention in mental events.

  15. Do focal colors look particularly "colorful"?

    Science.gov (United States)

    Witzel, Christoph; Franklin, Anna

    2014-04-01

    If the most typical red, yellow, green, and blue were particularly colorful (i.e., saturated), they would "jump out to the eye." This would explain why even fundamentally different languages have distinct color terms for these focal colors, and why unique hues play a prominent role in subjective color appearance. In this study, the subjective saturation of 10 colors around each of these focal colors was measured through a pairwise matching task. Results show that subjective saturation changes systematically across hues in a way that is strongly correlated to the visual gamut, and exponentially related to sensitivity but not to focal colors.

  16. Focal pancreatic enlargement: differentiation between pancreatic adenocarcinoma and focal pancreatitis on CT and ERCP

    International Nuclear Information System (INIS)

    Kim, Eun Kyung; Kim, Ki Whang; Lee, Jong Tae; Kim, Hee Soo; Yoo, Hyung Sik; Yu, Jeong Sik; Yoon, Sang Wook

    1995-01-01

    To differentiate the pancreatic adenocarcinoma from focal pancreatitis on CT and ERCP in cases of focal pancreatic enlargement. We analysed CT findings of 66 patients of pancreatic adenocarcinoma (n = 45) or focal pancreatitis (n = 21) with respect to size, density, calcification, pancreatic or biliary duct dilatation, fat plane obliteration around the vessels, direction of retroperitoneal extension, lymphadenopathy, pseudocyst formation and atrophy of pancreas. ERCP available in 48 patients were analysed in respect to morphologic appearance of CBD and pancreatic duct, and distance between the two ducts. The patients in focal pancreatitis were younger with more common history of alcohol drinking. There was no statistical difference in calcifications of the mass (18% in the adenocarcinoma, 33% in the focal pancreatitis), but a tendency of denser, larger number of calcifications was noted in focal pancreatitis. The finding of fat plane obliteration around the vessels were more common in pancreatic adenocarcinoma, and fascial thickenings were more prominent in focal pancreatitis, although not statistically significant. On ERCP, there were no differential points of CBD, pancreatic duct morphology, but distance between the two ducts at the lesion center was more wider in focal pancreatitis. Differentiating focal pancreatitis from pancreatic adenocarcinoma is difficult. However, we should consider the possibility of focal pancreatitis in cases of patients with young age, having alcoholic history in association with CT findings of large numbers of and dense calcifications, and ERCP findings of prominent separation of two duct at the lesion center

  17. Reperfusion promotes mitochondrial dysfunction following focal cerebral ischemia in rats.

    Directory of Open Access Journals (Sweden)

    Jun Li

    Full Text Available BACKGROUND AND PURPOSE: Mitochondrial dysfunction has been implicated in the cell death observed after cerebral ischemia, and several mechanisms for this dysfunction have been proposed. Reperfusion after transient cerebral ischemia may cause continued and even more severe damage to the brain. Many lines of evidence have shown that mitochondria suffer severe damage in response to ischemic injury. The purpose of this study was to observe the features of mitochondrial dysfunction in isolated mitochondria during the reperfusion period following focal cerebral ischemia. METHODS: Male Wistar rats were subjected to focal cerebral ischemia. Mitochondria were isolated using Percoll density gradient centrifugation. The isolated mitochondria were fixed for electron microscopic examination; calcium-induced mitochondrial swelling was quantified using spectrophotometry. Cyclophilin D was detected by Western blotting. Fluorescent probes were used to selectively stain mitochondria to measure their membrane potential and to measure reactive oxidative species production using flow cytometric analysis. RESULTS: Signs of damage were observed in the mitochondrial morphology after exposure to reperfusion. The mitochondrial swelling induced by Ca(2+ increased gradually with the increasing calcium concentration, and this tendency was exacerbated as the reperfusion time was extended. Cyclophilin D protein expression peaked after 24 hours of reperfusion. The mitochondrial membrane potential was decreased significantly during the reperfusion period, with the greatest decrease observed after 24 hours of reperfusion. The surge in mitochondrial reactive oxidative species occurred after 2 hours of reperfusion and was maintained at a high level during the reperfusion period. CONCLUSIONS: Reperfusion following focal cerebral ischemia induced significant mitochondrial morphological damage and Ca(2+-induced mitochondrial swelling. The mechanism of this swelling may be mediated by

  18. Focal skin defect, limb anomalies and microphthalmia.

    NARCIS (Netherlands)

    Jackson, K.E.; Andersson, H.C.

    2004-01-01

    We describe two unrelated female patients with congenital single focal skin defects, unilateral microphthalmia and limb anomalies. Growth and psychomotor development were normal and no brain malformation was detected. Although eye and limb anomalies are commonly associated, clinical anophthalmia and

  19. Focal adhesions and cell-matrix interactions

    DEFF Research Database (Denmark)

    Woods, A; Couchman, J R

    1988-01-01

    Focal adhesions are areas of cell surfaces where specializations of cytoskeletal, membrane and extracellular components combine to produce stable cell-matrix interactions. The morphology of these adhesions and the components identified in them are discussed together with possible mechanisms...

  20. Genetics Home Reference: focal dermal hypoplasia

    Science.gov (United States)

    ... in people with focal dermal hypoplasia is an omphalocele , which is an opening in the wall of ... Dermal Hypoplasia MedlinePlus Encyclopedia: Ectodermal dysplasia MedlinePlus Encyclopedia: Omphalocele General Information from MedlinePlus (5 links) Diagnostic Tests ...

  1. Implementation of focal zooming on the Nike KrF laser

    Energy Technology Data Exchange (ETDEWEB)

    Kehne, D. M.; Karasik, M.; Weaver, J. L.; Chan, Y.; Obenschain, S. P. [Plasma Physics Division, Naval Research Laboratory, Washington, DC 20375 (United States); Aglitsky, Y. [Science Applications International, McLean, Virginia 22150 (United States); Smyth, Z.; Lehmberg, R. H. [Research Support Instruments, Inc., Lanham, Maryland 20706 (United States); Terrell, S. [Commonwealth Technologies, Inc., Alexandria, Virginia 22315 (United States)

    2013-01-15

    In direct drive inertial confinement laser fusion, a pellet containing D-T fuel is imploded by ablation arising from absorption of laser energy at its outer surface. For optimal coupling, the focal spot of the laser would continuously decrease to match the reduction in the pellet's diameter, thereby minimizing wasted energy. A krypton-fluoride laser ({lambda}= 248 nm) that incorporates beam smoothing by induced spatial incoherence has the ability to produce a high quality focal profile whose diameter varies with time, a property known as focal zooming. A two-stage focal zoom has been demonstrated on the Nike laser at the Naval Research Laboratory. In the experiment, a 4.4 ns laser pulse was created in which the on-target focal spot diameter was 1.3 mm (full width at half maximum) for the first 2.4 ns and 0.28 mm for the final 2 ns. These two diameters appear in time-integrated focal plane equivalent images taken at several locations in the amplification chain. Eight of the zoomed output beams were overlapped on a 60 {mu}m thick planar polystyrene target. Time resolved images of self-emission from the rear of the target show the separate shocks launched by the two corresponding laser focal diameters.

  2. Implementation of focal zooming on the Nike KrF laser

    International Nuclear Information System (INIS)

    Kehne, D. M.; Karasik, M.; Weaver, J. L.; Chan, Y.; Obenschain, S. P.; Aglitsky, Y.; Smyth, Z.; Lehmberg, R. H.; Terrell, S.

    2013-01-01

    In direct drive inertial confinement laser fusion, a pellet containing D-T fuel is imploded by ablation arising from absorption of laser energy at its outer surface. For optimal coupling, the focal spot of the laser would continuously decrease to match the reduction in the pellet's diameter, thereby minimizing wasted energy. A krypton-fluoride laser (λ= 248 nm) that incorporates beam smoothing by induced spatial incoherence has the ability to produce a high quality focal profile whose diameter varies with time, a property known as focal zooming. A two-stage focal zoom has been demonstrated on the Nike laser at the Naval Research Laboratory. In the experiment, a 4.4 ns laser pulse was created in which the on-target focal spot diameter was 1.3 mm (full width at half maximum) for the first 2.4 ns and 0.28 mm for the final 2 ns. These two diameters appear in time-integrated focal plane equivalent images taken at several locations in the amplification chain. Eight of the zoomed output beams were overlapped on a 60 μm thick planar polystyrene target. Time resolved images of self-emission from the rear of the target show the separate shocks launched by the two corresponding laser focal diameters.

  3. Implementation of focal zooming on the Nike KrF laser

    Science.gov (United States)

    Kehne, D. M.; Karasik, M.; Aglitsky, Y.; Smyth, Z.; Terrell, S.; Weaver, J. L.; Chan, Y.; Lehmberg, R. H.; Obenschain, S. P.

    2013-01-01

    In direct drive inertial confinement laser fusion, a pellet containing D-T fuel is imploded by ablation arising from absorption of laser energy at its outer surface. For optimal coupling, the focal spot of the laser would continuously decrease to match the reduction in the pellet's diameter, thereby minimizing wasted energy. A krypton-fluoride laser (λ = 248 nm) that incorporates beam smoothing by induced spatial incoherence has the ability to produce a high quality focal profile whose diameter varies with time, a property known as focal zooming. A two-stage focal zoom has been demonstrated on the Nike laser at the Naval Research Laboratory. In the experiment, a 4.4 ns laser pulse was created in which the on-target focal spot diameter was 1.3 mm (full width at half maximum) for the first 2.4 ns and 0.28 mm for the final 2 ns. These two diameters appear in time-integrated focal plane equivalent images taken at several locations in the amplification chain. Eight of the zoomed output beams were overlapped on a 60 μm thick planar polystyrene target. Time resolved images of self-emission from the rear of the target show the separate shocks launched by the two corresponding laser focal diameters.

  4. Achromatic Focal Plane Mask for Exoplanet Imaging Coronagraphy

    Science.gov (United States)

    Newman, Kevin Edward; Belikov, Ruslan; Guyon, Olivier; Balasubramanian, Kunjithapatham; Wilson, Dan

    2013-01-01

    Recent advances in coronagraph technologies for exoplanet imaging have achieved contrasts close to 1e10 at 4 lambda/D and 1e-9 at 2 lambda/D in monochromatic light. A remaining technological challenge is to achieve high contrast in broadband light; a challenge that is largely limited by chromaticity of the focal plane mask. The size of a star image scales linearly with wavelength. Focal plane masks are typically the same size at all wavelengths, and must be sized for the longest wavelength in the observational band to avoid starlight leakage. However, this oversized mask blocks useful discovery space from the shorter wavelengths. We present here the design, development, and testing of an achromatic focal plane mask based on the concept of optical filtering by a diffractive optical element (DOE). The mask consists of an array of DOE cells, the combination of which functions as a wavelength filter with any desired amplitude and phase transmission. The effective size of the mask scales nearly linearly with wavelength, and allows significant improvement in the inner working angle of the coronagraph at shorter wavelengths. The design is applicable to almost any coronagraph configuration, and enables operation in a wider band of wavelengths than would otherwise be possible. We include initial results from a laboratory demonstration of the mask with the Phase Induced Amplitude Apodization coronagraph.

  5. Sighting optics including an optical element having a first focal length and a second focal length

    Science.gov (United States)

    Crandall, David Lynn [Idaho Falls, ID

    2011-08-01

    One embodiment of sighting optics according to the teachings provided herein may include a front sight and a rear sight positioned in spaced-apart relation. The rear sight includes an optical element having a first focal length and a second focal length. The first focal length is selected so that it is about equal to a distance separating the optical element and the front sight and the second focal length is selected so that it is about equal to a target distance. The optical element thus brings into simultaneous focus, for a user, images of the front sight and the target.

  6. PPARγ agonist pioglitazone reduces matrix metalloproteinase-9 activity and neuronal damage after focal cerebral ischemia

    International Nuclear Information System (INIS)

    Lee, Seong-Ryong; Kim, Hahn-Young; Hong, Jung-Suk; Baek, Won-Ki; Park, Jong-Wook

    2009-01-01

    Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, has shown protective effects against ischemic insult in various tissues. Pioglitazone is also reported to reduce matrix metalloproteinase (MMP) activity. MMPs can remodel extracellular matrix components in many pathological conditions. The current study was designed to investigate whether the neuroprotection of pioglitazone is related to its MMP inhibition in focal cerebral ischemia. Mice were subjected to 90 min focal ischemia and reperfusion. In gel zymography, pioglitazone reduced the upregulation of active form of MMP-9 after ischemia. In in situ zymograms, pioglitazone also reduced the gelatinase activity induced by ischemia. After co-incubation with pioglitazone, in situ gelatinase activity was directly reduced. Pioglitazone reduced the infarct volume significantly compared with controls. These results demonstrate that pioglitazone may reduce MMP-9 activity and neuronal damage following focal ischemia. The reduction of MMP-9 activity may have a possible therapeutic effect for the management of brain injury after focal ischemia.

  7. Electric field depth-focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs.

    Science.gov (United States)

    Deng, Zhi-De; Lisanby, Sarah H; Peterchev, Angel V

    2013-01-01

    Various transcranial magnetic stimulation (TMS) coil designs are available or have been proposed. However, key coil characteristics such as electric field focality and attenuation in depth have not been adequately compared. Knowledge of the coil focality and depth characteristics can help TMS researchers and clinicians with coil selection and interpretation of TMS studies. To quantify the electric field focality and depth of penetration of various TMS coils. The electric field distributions induced by 50 TMS coils were simulated in a spherical human head model using the finite element method. For each coil design, we quantified the electric field penetration by the half-value depth, d(1/2), and focality by the tangential spread, S(1/2), defined as the half-value volume (V(1/2)) divided by the half-value depth, S(1/2) = V(1/2)/d(1/2). The 50 TMS coils exhibit a wide range of electric field focality and depth, but all followed a depth-focality tradeoff: coils with larger half-value depth cannot be as focal as more superficial coils. The ranges of achievable d(1/2) are similar between coils producing circular and figure-8 electric field patterns, ranging 1.0-3.5 cm and 0.9-3.4 cm, respectively. However, figure-8 field coils are more focal, having S(1/2) as low as 5 cm(2) compared to 34 cm(2) for circular field coils. For any coil design, the ability to directly stimulate deeper brain structures is obtained at the expense of inducing wider electrical field spread. Novel coil designs should be benchmarked against comparison coils with consistent metrics such as d(1/2) and S(1/2). Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Modeling characterization of the National Ignition Facility focal spot

    International Nuclear Information System (INIS)

    Williams, W.H.

    1998-01-01

    The predicted focal spot size of the National Ignition Facility laser is parameterized against the finish quality of the optics in the system. Results are reported from simulations which include static optics aberrations, as well as pump-induced distortions, beam self-focusing, and the effect of an adaptive optic. The simulations do not include contributions from optics mounting errors, residual thermal noise in laser slabs from previous shots, air turbulence, a kinoform phase plate, or smoothing by spectral dispersion (SSD). Consequently, these results represent ''first shot of the day'', without-SSD, predictions

  9. Transparent meta-analysis: does aging spare prospective memory with focal vs. non-focal cues?

    Directory of Open Access Journals (Sweden)

    Bob Uttl

    Full Text Available BACKGROUND: Prospective memory (ProM is the ability to become aware of a previously-formed plan at the right time and place. For over twenty years, researchers have been debating whether prospective memory declines with aging or whether it is spared by aging and, most recently, whether aging spares prospective memory with focal vs. non-focal cues. Two recent meta-analyses examining these claims did not include all relevant studies and ignored prevalent ceiling effects, age confounds, and did not distinguish between prospective memory subdomains (e.g., ProM proper, vigilance, habitual ProM (see Uttl, 2008, PLoS ONE. The present meta-analysis focuses on the following questions: Does prospective memory decline with aging? Does prospective memory with focal vs. non-focal cues decline with aging? Does the size of age-related declines with focal vs. non-focal cues vary across ProM subdomains? And are age-related declines in ProM smaller than age-related declines in retrospective memory? METHODS AND FINDINGS: A meta-analysis of event-cued ProM using data visualization and modeling, robust count methods, and conventional meta-analysis techniques revealed that first, the size of age-related declines in ProM with both focal and non-focal cues are large. Second, age-related declines in ProM with focal cues are larger in ProM proper and smaller in vigilance. Third, age-related declines in ProM proper with focal cues are as large as age-related declines in recall measures of retrospective memory. CONCLUSIONS: The results are consistent with Craik's (1983 proposal that age-related declines on ProM tasks are generally large, support the distinction between ProM proper vs. vigilance, and directly contradict widespread claims that ProM, with or without focal cues, is spared by aging.

  10. Focal thyroid inferno” on color Doppler ultrasonography: A specific feature of focal Hashimoto's thyroiditis

    International Nuclear Information System (INIS)

    Fu, Xianshui; Guo, Limei; Zhang, Huabin; Ran, Weiqiang; Fu, Peng; Li, Zhiqiang; Chen, Wen; Jiang, Ling; Wang, Jinrui; Jia, Jianwen

    2012-01-01

    Purpose: To evaluate color-Doppler features predictive of focal Hashimoto's thyroiditis. Materials and methods: A total of 521 patients with 561 thyroid nodules that underwent surgeries or gun biopsies were included in this study. These nodules were divided into three groups: focal Hashimoto's thyroiditis (104 nodules in 101 patients), benignity other than focal Hashimoto's thyroiditis (73 nodules in 70 patients), and malignancy (358 nodules in 350 patients). On color Doppler sonography, four vascularity types were determined as: hypovascularity, marked internal flow, marked peripheral flow and focal thyroid inferno. The χ 2 test was performed to seek the potential vascularity type with the predictive ability of certain thyroid pathology. Furthermore, the gray-scale features of each nodule were also studied. Results: The vascularity type I (hypovascularity) was more often seen in focal Hashimoto's thyroiditis than other benignity and malignancy (46% vs. 20.5% and 19%). While the type II (marked internal flow) showed the opposite tendency (26.9% [focal Hashimoto's thyroiditis] vs. 45.2% [other benignity] and 52.8% [malignancy]). However, type III (marked peripheral flow) was unable to predict any thyroid pathology. Importantly, type IV (focal thyroid inferno) was exclusive to focal Hashimoto's thyroiditis. All 8 type IV nodules appeared to be solid, hypoechoic, and well-defined. Using “focal thyroid inferno” as an indicator of FHT, the diagnostic sensitivity and specificity were 7.7% and 100% respectively. Conclusions: The vascularity type of “focal thyroid inferno” is specific for focal Hashimoto thyroiditis. Recognition of this particular feature may avoid unnecessary interventional procedures for some solid hypoechoic thyroid nodules suspicious of malignancy.

  11. Prenatal sonographic diagnosis of focal musculoskeletal anomalies

    International Nuclear Information System (INIS)

    Ryu, Jung-Kyu; Cho, Jeong-Yeon; Choi, Jong-Sun

    2003-01-01

    Focal musculoskeletal anomalies vary, and can manifest as part of a syndrome or be accompanied by numerous other conditions such as genetic disorders, karyotype abnormalities, central nervous system anomalies and other skeletal anomalies, lsolated focal musculoskeletal anomaly does, however, also occur; its early prenatal diagnosis is important in deciding prenatal care, and also helps in counseling parents about the postnatal effects of numerous possible associated anomalies. We have encountered 50 cases involving focal musculoskeletal anomalies, including total limb dysplasia [radial ray abnormality (n=3), mesomelic dysplasia (n=1)]; anomalies of the hand [polydactyly (n=8), syndactyly (n=3), ectrodactyly (n=1), clinodactyly (n=6), clenched hand (n=5)]; anomalies of the foot [clubfoot (n=10), rockerbottom foot (n=5), sandal gap deformity (n=1), curly toe (n=2)]; amniotic band syndrome (n=3); and anomalies of the focal spine [block vertebra (n=1), hemivertebra (n=1)]. Among these 50 cases, five [polydactyly (n=1), syndactyly (n=2) and curly toe (n=2) were confirmed by postnatal physical evaluation, two (focal spine anomalies) were diagnosed after postnatal radiologic examination, and the remaining 43 were proven at autopsy. For each condition, we describe the prenatal sonographic findings, and include a brief review

  12. Prenatal sonographic diagnosis of focal musculoskeletal anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jung-Kyu; Cho, Jeong-Yeon; Choi, Jong-Sun [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2003-12-15

    Focal musculoskeletal anomalies vary, and can manifest as part of a syndrome or be accompanied by numerous other conditions such as genetic disorders, karyotype abnormalities, central nervous system anomalies and other skeletal anomalies, lsolated focal musculoskeletal anomaly does, however, also occur; its early prenatal diagnosis is important in deciding prenatal care, and also helps in counseling parents about the postnatal effects of numerous possible associated anomalies. We have encountered 50 cases involving focal musculoskeletal anomalies, including total limb dysplasia [radial ray abnormality (n=3), mesomelic dysplasia (n=1)]; anomalies of the hand [polydactyly (n=8), syndactyly (n=3), ectrodactyly (n=1), clinodactyly (n=6), clenched hand (n=5)]; anomalies of the foot [clubfoot (n=10), rockerbottom foot (n=5), sandal gap deformity (n=1), curly toe (n=2)]; amniotic band syndrome (n=3); and anomalies of the focal spine [block vertebra (n=1), hemivertebra (n=1)]. Among these 50 cases, five [polydactyly (n=1), syndactyly (n=2) and curly toe (n=2) were confirmed by postnatal physical evaluation, two (focal spine anomalies) were diagnosed after postnatal radiologic examination, and the remaining 43 were proven at autopsy. For each condition, we describe the prenatal sonographic findings, and include a brief review.

  13. Seven tesla MRI improves detection of focal cortical dysplasia in patients with refractory focal epilepsy

    NARCIS (Netherlands)

    Veersema, Tim J; Ferrier, Cyrille H; van Eijsden, Pieter; Gosselaar, Peter H; Aronica, Eleonora; Visser, Fredy; Zwanenburg, Jaco M; de Kort, Gerard A P; Hendrikse, Jeroen; Luijten, Peter R; Braun, Kees P J

    Objective: The aim of this study is to determine whether the use of 7 tesla (T) MRI in clinical practice leads to higher detection rates of focal cortical dysplasias in possible candidates for epilepsy surgery. Methods: In our center patients are referred for 7 T MRI if lesional focal epilepsy is

  14. Elevated circulating plasma endothelin-1 concentrations in cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Emmeluth, C; Henriksen, Jens Henrik

    1993-01-01

    veins on the one hand and the femoral artery on the other (P > 0.1), indicating no major net elimination or release in the liver, kidney or lower limb. A significant negative correlation was found between systolic and diastolic blood pressures on the one hand and circulating ET-1 on the other (r = -0.......70, P vein catheterization (n = 8), no significant differences were found in ET-1 plasma concentration between the liver, renal, or femoral...

  15. Expansive focal cemento-osseous dysplasia.

    Science.gov (United States)

    Bulut, Emel Uzun; Acikgoz, Aydan; Ozan, Bora; Zengin, Ayse Zeynep; Gunhan, Omer

    2012-01-01

    To present a case of expansive focal cemento-osseous dysplasia and emphasize the importance of differential diagnosis. Cemento-osseous dysplasia is categorized into three subtypes on the basis of the clinical and radiographic features: Periapical, focal and florid. The focal type exhibits a single site of involvement in any tooth-bearing or edentulous area of the jaws. These lesions are usually asymptomatic; therefore, they are frequently diagnosed incidentally during routine radiographic examinations. Lesions are usually benign, show limited growth, and do not require further surgical intervention, but periodic follow-up is recommended because occasionally, this type of dysplasia progresses into florid osseous dysplasia and simple bone cysts are formed. A 24-year-old female patient was referred to our clinic for swelling in the left edentulous mandibular premolarmolar region and felt discomfort when she wore her prosthetics. She had no pain, tenderness or paresthesia. Clinical examination showed that the swelling in the posterior mandible that was firm, nonfluctuant and covered by normal mucosa. On panoramic radiography and computed tomography, a well defined lesion of approximately 1.5 cm in diameter of mixed density was observed. The swelling increased slightly in size over 2 years making it difficult to use prosthetics and, therefore, the lesion was totally excised under local anesthesia, and surgical specimens were submitted for histopathological examination. The histopathological diagnosis was focal cemento-osseous dysplasia. In the present case, because of the increasing size of the swelling making it difficult to use prosthetics, young age of the patient and localization of the lesion, in the initial examination, cemento-ossifying fibroma was suspected, and the lesion was excised surgically; the histopathological diagnosis confirmed it as focal cemento-osseous dysplasia. We present a case of expansive focal cemento-osseous dysplasia. Differential diagnosis

  16. HIGH PERFORMANCE PIAA CORONAGRAPHY WITH COMPLEX AMPLITUDE FOCAL PLANE MASKS

    International Nuclear Information System (INIS)

    Guyon, Olivier; Martinache, Frantz; Belikov, Ruslan; Soummer, Remi

    2010-01-01

    We describe a coronagraph approach where the performance of a Phase-Induced Amplitude Apodization (PIAA) coronagraph is improved by using a partially transmissive phase-shifting focal plane mask and a Lyot stop. This approach combines the low inner working angle offered by phase mask coronagraphy, the full throughput and uncompromized angular resolution of the PIAA approach, and the design flexibility of Apodized Pupil Lyot Coronagraph. A PIAA complex mask coronagraph (PIAACMC) is fully described by the focal plane mask size, or, equivalently, its complex transmission which ranges from 0 (opaque) to -1 (phase shifting). For all values of the transmission, the PIAACMC theoretically offers full on-axis extinction and 100% throughput at large angular separations. With a pure phase focal plane mask (complex transmission = -1), the PIAACMC offers 50% throughput at 0.64 λ/D while providing total extinction of an on-axis point source. This performance is very close to the 'fundamental performance limit' of coronagraphy derived from first principles. For very high contrast level, imaging performance with PIAACMC is in practice limited by the angular size of the on-axis target (usually a star). We show that this fundamental limitation must be taken into account when choosing the optimal value of the focal plane mask size in the PIAACMC design. We show that the PIAACMC enables visible imaging of Jupiter-like planets at ∼1.2 λ/D from the host star, and can therefore offer almost three times more targets than a PIAA coronagraph optimized for this type of observation. We find that for visible imaging of Earth-like planets, the PIAACMC gain over a PIAA is probably much smaller, as coronagraphic performance is then strongly constrained by stellar angular size. For observations at 'low' contrast (below ∼ 10 8 ), the PIAACMC offers significant performance enhancement over PIAA. This is especially relevant for ground-based high contrast imaging systems in the near-IR, where

  17. BID Mediates Oxygen-Glucose Deprivation-Induced Neuronal Injury in Organotypic Hippocampal Slice Cultures and Modulates Tissue Inflammation in a Transient Focal Cerebral Ischemia Model without Changing Lesion Volume

    DEFF Research Database (Denmark)

    Martin, Nellie Anne; Bonner, Helena; Elkjær, Maria Louise

    2016-01-01

    The BH3 interacting-domain death agonist (BID) is a pro-apoptotic protein involved in death receptor-induced and mitochondria-mediated apoptosis. Recently, it has also been suggested that BID is involved in the regulation of inflammatory responses in the central nervous system. We found that BID...

  18. Extensive Focal Epithelial Hyperplasia: A Case Report.

    Science.gov (United States)

    Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

    2015-01-01

    Focal epithelial hyperplasia (FEH) or Heck's disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis.

  19. Rasmussen's encephalitis presenting as focal cortical dysplasia

    Directory of Open Access Journals (Sweden)

    D.J. O'Rourke

    2014-01-01

    Full Text Available Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD and discuss the literature on this topic.

  20. Rasmussen's encephalitis presenting as focal cortical dysplasia

    Science.gov (United States)

    O'Rourke, D.J.; Bergin, A.; Rotenberg, A.; Peters, J.; Gorman, M.; Poduri, A.; Cryan, J.; Lidov, H.; Madsen, J.; Harini, C.

    2014-01-01

    Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD) and discuss the literature on this topic. PMID:25667877

  1. Actinic Granuloma with Focal Segmental Glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Ruedee Phasukthaworn

    2016-02-01

    Full Text Available Actinic granuloma is an uncommon granulomatous disease, characterized by annular erythematous plaque with central clearing predominately located on sun-damaged skin. The pathogenesis is not well understood, ultraviolet radiation is recognized as precipitating factor. We report a case of a 52-year-old woman who presented with asymptomatic annular erythematous plaques on the forehead and both cheeks persisting for 2 years. The clinical presentation and histopathologic findings support the diagnosis of actinic granuloma. During that period of time, she also developed focal segmental glomerulosclerosis. The association between actinic granuloma and focal segmental glomerulosclerosis needs to be clarified by further studies.

  2. 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

  3. Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1.

    Science.gov (United States)

    Sada, Kiminori; Nishikawa, Takeshi; Kukidome, Daisuke; Yoshinaga, Tomoaki; Kajihara, Nobuhiro; Sonoda, Kazuhiro; Senokuchi, Takafumi; Motoshima, Hiroyuki; Matsumura, Takeshi; Araki, Eiichi

    2016-01-01

    We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs), cellular hypoxia increased after incubation with high glucose (HG). A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD) overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1), a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.

  4. Performance of an Achromatic Focal Plane Mask for Exoplanet Imaging Coronagraphy

    Science.gov (United States)

    Newman, Kevin; Belikov, Ruslan; Pluzhnik, Eugene; Balasubramanian, Kunjithapatham; Wilson, Dan

    2014-01-01

    Coronagraph technology combined with wavefront control is close to achieving the contrast and inner working angle requirements in the lab necessary to observe the faint signal of an Earth-like exoplanet in monochromatic light. An important remaining technological challenge is to achieve high contrast in broadband light. Coronagraph bandwidth is largely limited by chromaticity of the focal plane mask, which is responsible for blocking the stellar PSF. The size of a stellar PSF scales linearly with wavelength; ideally, the size of the focal plane mask would also scale with wavelength. A conventional hard-edge focal plane mask has a fixed size, normally sized for the longest wavelength in the observational band to avoid starlight leakage. The conventional mask is oversized for shorter wavelengths and blocks useful discovery space. Recently we presented a solution to the size chromaticity challenge with a focal plane mask designed to scale its effective size with wavelength. In this paper, we analyze performance of the achromatic size-scaling focal plane mask within a Phase Induced Amplitude Apodization (PIAA) coronagraph. We present results from wavefront control around the achromatic focal plane mask, and demonstrate the size-scaling effect of the mask with wavelength. The edge of the dark zone, and therefore the inner working angle of the coronagraph, scale with wavelength. The achromatic mask enables operation in a wider band of wavelengths compared with a conventional hard-edge occulter.

  5. Transcranial Magnetic Stimulation-coil design with improved focality

    Science.gov (United States)

    Rastogi, P.; Lee, E. G.; Hadimani, R. L.; Jiles, D. C.

    2017-05-01

    Transcranial Magnetic Stimulation (TMS) is a technique for neuromodulation that can be used as a non-invasive therapy for various neurological disorders. In TMS, a time varying magnetic field generated from an electromagnetic coil placed on the scalp is used to induce an electric field inside the brain. TMS coil geometry plays an important role in determining the focality and depth of penetration of the induced electric field responsible for stimulation. Clinicians and basic scientists are interested in stimulating a localized area of the brain, while minimizing the stimulation of surrounding neural networks. In this paper, a novel coil has been proposed, namely Quadruple Butterfly Coil (QBC) with an improved focality over the commercial Figure-8 coil. Finite element simulations were conducted with both the QBC and the conventional Figure-8 coil. The two coil's stimulation profiles were assessed with 50 anatomically realistic MRI derived head models. The coils were positioned on the vertex and the scalp over the dorsolateral prefrontal cortex to stimulate the brain. Computer modeling of the coils has been done to determine the parameters of interest-volume of stimulation, maximum electric field, location of maximum electric field and area of stimulation across all 50 head models for both coils.

  6. Combined baseline and one-month changes in big endothelin-1 and brain natriuretic peptide plasma concentrations predict clinical outcomes in patients with left ventricular dysfunction after acute myocardial infarction: Insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) study.

    Science.gov (United States)

    Olivier, A; Girerd, N; Michel, J B; Ketelslegers, J M; Fay, R; Vincent, J; Bramlage, P; Pitt, B; Zannad, F; Rossignol, P

    2017-08-15

    Increased levels of neuro-hormonal biomarkers predict poor prognosis in patients with acute myocardial infarction (AMI) complicated by left ventricular systolic dysfunction (LVSD). The predictive value of repeated (one-month interval) brain natriuretic peptides (BNP) and big-endothelin 1 (BigET-1) measurements were investigated in patients with LVSD after AMI. In a sub-study of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS trial), BNP and BigET-1 were measured at baseline and at 1month in 476 patients. When included in the same Cox regression model, baseline BNP (p=0.0003) and BigET-1 (p=0.026) as well as the relative changes (after 1month) from baseline in BNP (p=0.049) and BigET-1 (p=0.045) were predictive of the composite of cardiovascular death or hospitalization for worsening heart failure. Adding baseline and changes in BigET-1 to baseline and changes in BNP led to a significant increase in prognostic reclassification as assessed by integrated discrimination improvement index (5.0%, p=0.01 for the primary endpoint). Both increased baseline and changes after one month in BigET-1 concentrations were shown to be associated with adverse clinical outcomes, independently from BNP baseline levels and one month changes, in patients after recent AMI complicated with LVSD. This novel result may be of clinical interest since such combined biomarker assessment could improve risk stratification and open new avenues for biomarker-guided targeted therapies. In the present study, we report for the first time in a population of patients with reduced LVEF after AMI and signs or symptoms of congestive HF, that increased baseline values of BNP and BigET-1 as well as a further rise of these markers over the first month after AMI, were independently predictive of future cardiovascular events. This approach may therefore be of clinical interest with the potential of improving risk stratification after AMI with reduced LVEF while

  7. Infrared MUSIC from Z technology focal planes

    International Nuclear Information System (INIS)

    Waters, C.R.; Sommese, A.; Johnston, D.; Landau, H.

    1989-01-01

    Presented is the Multiple Signal Classification (MUSIC) algorithm which uses the high frequency differences in sensed time signals to discriminate, count, and accurately locate closely spaced targets. Z technology focal planes allow the implementation of this algorithm and the trade-off between finer spatial resolution systems and systems with coarser resolution but higher sampling rates

  8. Focal dermal hypoplasia: A rare case report

    Directory of Open Access Journals (Sweden)

    Sahana M Srinivas

    2015-01-01

    Full Text Available Focal dermal hypoplasia (Goltz syndrome is a rare genetic multisystem disorder primarily involving the skin, skeletal system, eyes, and face. We report the case of an eight-month-old female child who presented with multiple hypopigmented atrophic macules along the lines of blaschko, skeletal anomalies, umbilical hernia, developmental delay, hypoplastic nails, syndactyly, and lobster claw deformity characteristic of Goltz syndrome.

  9. High Dynamic Range adaptive ΔΣ-based Focal Plane Array architecture

    KAUST Repository

    Yao, Shun; Kavusi, Sam; Salama, Khaled N.

    2012-01-01

    In this paper, an Adaptive Delta-Sigma based architecture for High Dynamic Range (HDR) Focal Plane Arrays is presented. The noise shaping effect of the Delta-Sigma modulation in the low end, and the distortion noise induced in the high end of Photo

  10. Induction of interleukin-1β mRNA after focal cerebral ischaemia in the rat

    NARCIS (Netherlands)

    Buttini, M.; Sauter, A.; Boddeke, H.W.G.M.

    1994-01-01

    The expression of interleukin-1β (IL-1β) mRNA in the brain in response to cerebral ischaemia in rats was examined using in situ hybridization histochemistry. Focal cerebral ischaemia was induced in spontaneously hypertensive rats by permanent occlusion of the left middle cerebral artery (MCAO).

  11. INDUCTION OF INTERLEUKIN-1-BETA MESSENGER-RNA AFTER FOCAL CEREBRAL-ISCHEMIA IN THE RAT

    NARCIS (Netherlands)

    BUTTINI, M; SAUTER, A; BODDEKE, HWGM

    The expression of interleukin-1beta (IL-1beta) mRNA in the brain in response to cerebral ischaemia in rats was examined using in situ hybridization histochemistry. Focal cerebral ischaemia was induced in spontaneously hypertensive rats by permanent occlusion of the left middle cerebral artery

  12. Selective Deletion of Leptin Signaling in Endothelial Cells Enhances Neointima Formation and Phenocopies the Vascular Effects of Diet-Induced Obesity in Mice.

    Science.gov (United States)

    Hubert, Astrid; Bochenek, Magdalena L; Schütz, Eva; Gogiraju, Rajinikanth; Münzel, Thomas; Schäfer, Katrin

    2017-09-01

    Obesity is associated with elevated circulating leptin levels and hypothalamic leptin resistance. Leptin receptors (LepRs) are expressed on endothelial cells, and leptin promotes neointima formation in a receptor-dependent manner. Our aim was to examine the importance of endothelial LepR (End.LepR) signaling during vascular remodeling and to determine whether the cardiovascular consequences of obesity are because of hyperleptinemia or endothelial leptin resistance. Mice with loxP-flanked LepR alleles were mated with mice expressing Cre recombinase controlled by the inducible endothelial receptor tyrosine kinase promoter. Obesity was induced with high-fat diet. Neointima formation was examined after chemical carotid artery injury. Morphometric quantification revealed significantly greater intimal hyperplasia, neointimal cellularity, and proliferation in End.LepR knockout mice, and similar findings were obtained in obese, hyperleptinemic End.LepR wild-type animals. Analysis of primary endothelial cells confirmed abrogated signal transducer and activator of transcription-3 phosphorylation in response to leptin in LepR knockout and obese LepR wild-type mice. Quantitative PCR, ELISA, and immunofluorescence analyses revealed increased expression and release of endothelin-1 in End.LepR-deficient and LepR-resistant cells, and ET receptor A/B antagonists abrogated their paracrine effects on murine aortic smooth muscle cell proliferation. Reduced expression of peroxisome proliferator-activated receptor-γ and increased nuclear activator protein-1 staining was observed in End.LepR-deficient and LepR-resistant cells, and peroxisome proliferator-activated receptor-γ antagonization increased endothelial endothelin-1 expression. Our findings suggest that intact endothelial leptin signaling limits neointima formation and that obesity represents a state of endothelial leptin resistance. These observations and the identification of endothelin-1 as soluble mediator of the

  13. DESI focal plate mechanical integration and cooling

    Science.gov (United States)

    Lambert, A. R.; Besuner, R. W.; Claybaugh, T. M.; Silber, J. H.

    2016-08-01

    The Dark Energy Spectroscopic Instrument (DESI) is under construction to measure the expansion history of the Universe using the Baryon Acoustic Oscillation technique[1]. The spectra of 40 million galaxies over 14000 sq. deg will be measured during the life of the experiment. A new prime focus corrector for the KPNO Mayall telescope will deliver light to 5000 fiber optic positioners. The fibers in turn feed ten broad-band spectrographs. This paper describes the mechanical integration of the DESI focal plate and the thermal system design. The DESI focal plate is comprised of ten identical petal assemblies. Each petal contains 500 robotic fiber positioners. Each petal is a complete, self-contained unit, independent from the others, with integrated power supply, controllers, fiber routing, and cooling services. The major advantages of this scheme are: (1) supports installation and removal of complete petal assemblies in-situ, without disturbing the others, (2) component production, assembly stations, and test procedures are repeated and parallelizable, (3) a complete, full-scale prototype can be built and tested at an early date, (4) each production petal can be surveyed and tested as a complete unit, prior to integration, from the fiber tip at the focal surface to the fiber slit at the spectrograph. The ten petal assemblies will be installed in a single integration ring, which is mounted to the DESI corrector. The aluminum integration ring attaches to the steel corrector barrel via a flexured steel adapter, isolating the focal plate from differential thermal expansions. The plate scale will be kept stable by conductive cooling of the petal assembly. The guider and wavefront sensors (one per petal) will be convectively cooled by forced flow of air. Heat will be removed from the system at ten liquid-cooled cold plates, one per petal, operating at ambient temperature. The entire focal plate structure is enclosed in an insulating shroud, which serves as a thermal barrier

  14. Single scan femtosecond laser transverse writing of depressed cladding waveguides enabled by three-dimensional focal field engineering.

    Science.gov (United States)

    Zhang, Qian; Yang, Dong; Qi, Jia; Cheng, Ya; Gong, Qihuang; Li, Yan

    2017-06-12

    We report single scan transverse writing of depressed cladding waveguides inside ZBLAN glass with the longitudinally oriented annular ring-shaped focal intensity distribution of the femtosecond laser. The entire region of depressed cladding at the cross section, where a negative change of refraction index is induced, can be modified simultaneously with the ring-shaped focal intensity profile. The fabricated waveguides exhibit good single guided mode.

  15. Radiopneumographic characteristics of focal pneumonia in children

    International Nuclear Information System (INIS)

    Smirnova, A.A.

    1980-01-01

    Zonal ventilation and blood flow were studied by the radiopneumography method in 50 children of school age with lower-lobe-of-the lung focal pneumonia (26 with left-side and 24 with right-side). It is established that during right-side localization of pneumonic focus preserved was the predomination of ventilation of right lung relative to left. Complete normalization of common and regional indexes of ventilation and blood flow was established by the 21st day from the beginning of treatment during right-side focal pneumonias. In case of left-side localization of pneumonic focus only partial reduction of external respiration and perfusion comes. Therefore, compensatory and reducing capabilities of right lung are preferrable

  16. Membership Functions for Fuzzy Focal Elements

    Directory of Open Access Journals (Sweden)

    Porębski Sebastian

    2016-09-01

    Full Text Available The paper presents a study on data-driven diagnostic rules, which are easy to interpret by human experts. To this end, the Dempster-Shafer theory extended for fuzzy focal elements is used. Premises of the rules (fuzzy focal elements are provided by membership functions which shapes are changing according to input symptoms. The main aim of the present study is to evaluate common membership function shapes and to introduce a rule elimination algorithm. Proposed methods are first illustrated with the popular Iris data set. Next experiments with five medical benchmark databases are performed. Results of the experiments show that various membership function shapes provide different inference efficiency but the extracted rule sets are close to each other. Thus indications for determining rules with possible heuristic interpretation can be formulated.

  17. Focal epilepsy in the Belgian shepherd

    DEFF Research Database (Denmark)

    Berendt, Mette; Gulløv, Christina Hedal; Fredholm, Merete

    2009-01-01

    and deceased) were ascertained through a telephone interview using a standardised questionnaire regarding seizure history and phenomenology. Living dogs were invited to a detailed clinical evaluation. Litters more than five years of age, or where epilepsy was present in all offspring before the age of five......, were included in the calculations of inheritance. results: Out of 199 family members, 66 dogs suffered from epilepsy. The prevalence of epilepsy in the family was 33%. Fifty-five dogs experienced focal seizures with or without secondary generalisation, while four dogs experienced primary generalised...... seizures. In seven dogs, seizures could not be classified. The mode of inheritance of epilepsy was simple Mendelian. CLINICAL SIGNIFICANCE: This study identified that the Belgian shepherd suffers from genetically transmitted focal epilepsy. The seizure phenomenology expressed by family members have...

  18. Chest pain in focal musculoskeletal disorders

    DEFF Research Database (Denmark)

    Stochkendahl, Mette Jensen; Christensen, Henrik Wulff

    2010-01-01

    overlapping conditions and syndromes of focal disorders, including Tietze syndrome, costochondritis, chest wall syndrome, muscle tenderness, slipping rib, cervical angina, and segmental dysfunction of the cervical and thoracic spine, have been reported to cause pain. For most of these syndromes, evidence......The musculoskeletal system is a recognized source of chest pain. However, despite the apparently benign origin, patients with musculoskeletal chest pain remain under-diagnosed, untreated, and potentially continuously disabled in terms of anxiety, depression, and activities of daily living. Several...... arises mainly from case stories and empiric knowledge. For segmental dysfunction, clinical features of musculoskeletal chest pain have been characterized in a few clinical trials. This article summarizes the most commonly encountered syndromes of focal musculoskeletal disorders in clinical practice....

  19. Evaluation of focused ultrasound algorithms: Issues for reducing pre-focal heating and treatment time.

    Science.gov (United States)

    Yiannakou, Marinos; Trimikliniotis, Michael; Yiallouras, Christos; Damianou, Christakis

    2016-02-01

    Due to the heating in the pre-focal field the delay between successive movements in high intensity focused ultrasound (HIFU) are sometimes as long as 60s, resulting to treatment time in the order of 2-3h. Because there is generally a requirement to reduce treatment time, we were motivated to explore alternative transducer motion algorithms in order to reduce pre-focal heating and treatment time. A 1 MHz single element transducer with 4 cm diameter and 10 cm focal length was used. A simulation model was developed that estimates the temperature, thermal dose and lesion development in the pre-focal field. The simulated temperature history that was combined with the motion algorithms produced thermal maps in the pre-focal region. Polyacrylimde gel phantom was used to evaluate the induced pre-focal heating for each motion algorithm used, and also was used to assess the accuracy of the simulation model. Three out of the six algorithms having successive steps close to each other, exhibited severe heating in the pre-focal field. Minimal heating was produced with the algorithms having successive steps apart from each other (square, square spiral and random). The last three algorithms were improved further (with small cost in time), thus eliminating completely the pre-focal heating and reducing substantially the treatment time as compared to traditional algorithms. Out of the six algorithms, 3 were successful in eliminating the pre-focal heating completely. Because these 3 algorithms required no delay between successive movements (except in the last part of the motion), the treatment time was reduced by 93%. Therefore, it will be possible in the future, to achieve treatment time of focused ultrasound therapies shorter than 30 min. The rate of ablated volume achieved with one of the proposed algorithms was 71 cm(3)/h. The intention of this pilot study was to demonstrate that the navigation algorithms play the most important role in reducing pre-focal heating. By evaluating in

  20. Characterization of LIL laser UV focal spot

    International Nuclear Information System (INIS)

    Mangeant, M.; Dubois, J.L.; Behar, G.; Arroyo, P.; Durand, V.; Lahonde, C.

    2006-01-01

    One way to get the fusion of hydrogen in laboratory consists in heating and compressing a DT fuel capsule by using a laser. To reach this aim requires a new generation of high power laser facility. Cea (French board for atomic energy) is developing for this purpose a new 240 laser line facility, the LMJ facility. The LIL which is the prototype of four LMJ laser lines is operational now. In order to confirm the technical choices, a systematic characterization of LIL was carried out. A particular effort has been provided to measure the 3ω high energy focal spot (1.5 kJ/700 ps and 5 ns for one beam) and the synchronization of laser beams onto the target, which are key issues for the plasma production. An experimental device, SAT-3ω (a 3ω laser focal spot analysis) has been designed to perform these measures. That diagnostic which is located at the end of the laser lines delivered its first results during the 2004 quadruplet qualification campaigns. The near field imaging showed no diaphony and vignetting. Low power spots allowed us to control we had no ghost. The energy measurement quality showed the photometric transfer function was perfectly known. Our caustic image are given with an average dynamic range of 800, a spatial resolution of 10 μm and diameter accuracy about 1% for 50% and 3% for 90% of encircled energy. The high energy focal spot diameters are in agreement with low and very low energy diameters. The phase plate and 14 GHz effects are similar to what we had expected. For a laser shot completed with a continuous phase plate at 14 GHz, and for an energy level of 1.5 kJ per beam at 351 nm, the focal beam diameter at 3% of the peak level is (875 ± 45) μm

  1. Proximal focal femoral deficiency: A case report

    Directory of Open Access Journals (Sweden)

    Shashank Sharma

    2015-01-01

    Full Text Available Proximal focal femoral deficiency (PFFD is a rare congenital anomaly resulting in limb shortening and disability in young. The exact cause of the disease is not known and it may present as varying grades of affection involving the proximal femur and the acetabulum. Recognition of this rare abnormality on radiographs can help manage these cases better since early institution of therapy may help in achieving adequate growth of the femur.

  2. Syndecan-4 and focal adhesion function

    DEFF Research Database (Denmark)

    Woods, A; Couchman, J R

    2001-01-01

    Two groups have now reported the viability of mice that lack syndecan-4. These mice have wound healing/angiogenesis problems, and fibroblasts from these animals differ in adhesion and migration from normal. This is consistent with recent in vitro data indicating a need for signaling via syndecan-4...... for focal adhesion formation, and reports that overexpression of proteins that bind syndecan-4 can modify cell adhesion and migration....

  3. Focal adhesions, stress fibers and mechanical tension

    Energy Technology Data Exchange (ETDEWEB)

    Burridge, Keith, E-mail: Keith_Burridge@med.unc.edu [Department of Cell Biology and Physiology, and Lineberger Comprehensive Cancer Center, 12-016 Lineberger, CB#7295, University of North Carolina, Chapel Hill, NC (United States); Guilluy, Christophe, E-mail: christophe.guilluy@univ-nantes.fr [Inserm UMR-S1087, CNRS UMR-C6291, L' institut du Thorax, and Université de Nantes, Nantes (France)

    2016-04-10

    Stress fibers and focal adhesions are complex protein arrays that produce, transmit and sense mechanical tension. Evidence accumulated over many years led to the conclusion that mechanical tension generated within stress fibers contributes to the assembly of both stress fibers themselves and their associated focal adhesions. However, several lines of evidence have recently been presented against this model. Here we discuss the evidence for and against the role of mechanical tension in driving the assembly of these structures. We also consider how their assembly is influenced by the rigidity of the substratum to which cells are adhering. Finally, we discuss the recently identified connections between stress fibers and the nucleus, and the roles that these may play, both in cell migration and regulating nuclear function. - Highlights: • The different types of stress fiber and focal adhesion are described. • We discuss the controversy about tension and assembly of these structures. • We describe the different models used to investigate assembly of these structures. • The influence of substratum rigidity is discussed. • Stress fiber connections to the nucleus are reviewed.

  4. Focal plane scanner with reciprocating spatial window

    Science.gov (United States)

    Mao, Chengye (Inventor)

    2000-01-01

    A focal plane scanner having a front objective lens, a spatial window for selectively passing a portion of the image therethrough, and a CCD array for receiving the passed portion of the image. All embodiments have a common feature whereby the spatial window and CCD array are mounted for simultaneous relative reciprocating movement with respect to the front objective lens, and the spatial window is mounted within the focal plane of the front objective. In a first embodiment, the spatial window is a slit and the CCD array is one-dimensional, and successive rows of the image in the focal plane of the front objective lens are passed to the CCD array by an image relay lens interposed between the slit and the CCD array. In a second embodiment, the spatial window is a slit, the CCD array is two-dimensional, and a prism-grating-prism optical spectrometer is interposed between the slit and the CCD array so as to cause the scanned row to be split into a plurality of spectral separations onto the CCD array. In a third embodiment, the CCD array is two-dimensional and the spatial window is a rectangular linear variable filter (LVF) window, so as to cause the scanned rows impinging on the LVF to be bandpass filtered into spectral components onto the CCD array through an image relay lens interposed between the LVF and the CCD array.

  5. Classification of Focal and Non Focal Epileptic Seizures Using Multi-Features and SVM Classifier.

    Science.gov (United States)

    Sriraam, N; Raghu, S

    2017-09-02

    Identifying epileptogenic zones prior to surgery is an essential and crucial step in treating patients having pharmacoresistant focal epilepsy. Electroencephalogram (EEG) is a significant measurement benchmark to assess patients suffering from epilepsy. This paper investigates the application of multi-features derived from different domains to recognize the focal and non focal epileptic seizures obtained from pharmacoresistant focal epilepsy patients from Bern Barcelona database. From the dataset, five different classification tasks were formed. Total 26 features were extracted from focal and non focal EEG. Significant features were selected using Wilcoxon rank sum test by setting p-value (p z > 1.96) at 95% significance interval. Hypothesis was made that the effect of removing outliers improves the classification accuracy. Turkey's range test was adopted for pruning outliers from feature set. Finally, 21 features were classified using optimized support vector machine (SVM) classifier with 10-fold cross validation. Bayesian optimization technique was adopted to minimize the cross-validation loss. From the simulation results, it was inferred that the highest sensitivity, specificity, and classification accuracy of 94.56%, 89.74%, and 92.15% achieved respectively and found to be better than the state-of-the-art approaches. Further, it was observed that the classification accuracy improved from 80.2% with outliers to 92.15% without outliers. The classifier performance metrics ensures the suitability of the proposed multi-features with optimized SVM classifier. It can be concluded that the proposed approach can be applied for recognition of focal EEG signals to localize epileptogenic zones.

  6. Multispectral linear array (MLA) focal plane mechanical and thermal design

    Science.gov (United States)

    Mitchell, A. S.; Kaminski, E. F.

    1982-01-01

    The mechanical and thermal design of an integrated focal plane subsystem of a Multispectral Linear Array (MLA) instrument is discussed in terms of focal-plane alignment, thermoelastic performance, and thermal requirements. The modular construction and thermal control of the focal plane array are discussed.

  7. Theory of the mechanical response of focal adhesions to shear flow

    International Nuclear Information System (INIS)

    Biton, Y Y; Safran, S A

    2010-01-01

    The response of cells to shear flow is primarily determined by the asymmetry of the external forces and moments that are sensed by each member of a focal adhesion pair connected by a contractile stress fiber. In the theory presented here, we suggest a physical model in which each member of such a pair of focal adhesions is treated as an elastic body subject to both a myosin-activated contractile force and the shear stress induced by the external flow. The elastic response of a focal adhesion complex is much faster than the active cellular processes that determine the size of the associated focal adhesions and the direction of the complex relative to the imposed flow. Therefore, the complex attains its mechanical equilibrium configuration which may change because of the cellular activity. Our theory is based on the experimental observation that focal adhesions modulate their cross-sectional area in order to attain an optimal shear. Using this assumption, our elastic model shows that such a complex can passively change its orientation to align parallel to the direction of the flow.

  8. Noninvasive transcranial focal stimulation via tripolar concentric ring electrodes lessens behavioral seizure activity of recurrent pentylenetetrazole administrations in rats.

    Science.gov (United States)

    Makeyev, Oleksandr; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Liu, Xiang; Besio, Walter G

    2013-05-01

    Epilepsy affects approximately 1% of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We have been developing a noninvasive transcranial focal electrical stimulation with our novel tripolar concentric ring electrodes as an alternative/complementary therapy for seizure control. In this study we demonstrate the effect of focal stimulation on behavioral seizure activity induced by two successive pentylenetetrazole administrations in rats. Seizure onset latency, time of the first behavioral change, duration of seizure, and maximal seizure severity score were studied and compared for focal stimulation treated (n = 9) and control groups (n = 10). First, we demonstrate that no significant difference was found in behavioral activity for focal stimulation treated and control groups after the first pentylenetetrazole administration. Next, comparing first and second pentylenetetrazole administrations, we demonstrate there was a significant change in behavioral activity (time of the first behavioral change) in both groups that was not related to focal stimulation. Finally, we demonstrate focal stimulation provoking a significant change in seizure onset latency, duration of seizure, and maximal seizure severity score. We believe that these results, combined with our previous reports, suggest that transcranial focal stimulation may have an anticonvulsant effect.

  9. Pseudomonas-derived ceramidase induces production of inflammatory mediators from human keratinocytes via sphingosine-1-phosphate.

    Directory of Open Access Journals (Sweden)

    Ami Oizumi

    Full Text Available Ceramide is important for water retention and permeability barrier functions in the stratum corneum, and plays a key role in the pathogenesis of atopic dermatitis (AD. A Pseudomonas aeruginosa-derived neutral ceramidase (PaCDase isolated from a patient with AD was shown to effectively degrade ceramide in the presence of Staphylococcus aureus-derived lipids or neutral detergents. However, the effect of ceramide metabolites on the functions of differentiating keratinocytes is poorly understood. We found that the ceramide metabolite sphingosine-1-phosphate (S1P stimulated the production of inflammatory mediators such as TNF-α and IL-8 from three-dimensionally cultured human primary keratinocytes (termed "3D keratinocytes", which form a stratum corneum. PaCDase alone did not affect TNF-α gene expression in 3D keratinocytes. In the presence of the detergent Triton X-100, which damages stratum corneum structure, PaCDase, but not heat-inactivated PaCDase or PaCDase-inactive mutant, induced the production of TNF-α, endothelin-1, and IL-8, indicating that this production was dependent on ceramidase activity. Among various ceramide metabolites, sphingosine and S1P enhanced the gene expression of TNF-α, endothelin-1, and IL-8. The PaCDase-enhanced expression of these genes was inhibited by a sphingosine kinase inhibitor and by an S1P receptor antagonist VPC 23019. The TNF-α-binding antibody infliximab suppressed the PaCDase-induced upregulation of IL-8, but not TNF-α, mRNA. PaCDase induced NF-κB p65 phosphorylation. The NF-κB inhibitor curcumin significantly inhibited PaCDase-induced expression of IL-8 and endothelin-1. VPC 23019 and infliximab inhibited PaCDase-induced NF-κB p65 phosphorylation and reduction in the protein level of the NF-κB inhibitor IκBα. Collectively, these findings suggest that (i 3D keratinocytes produce S1P from sphingosine, which is produced through the hydrolysis of ceramide by PaCDase, (ii S1P induces the production

  10. The Simbol-X Focal Plane

    Science.gov (United States)

    Laurent, P.

    2009-05-01

    The Simbol-X focal plane is designed to detect photons focused by the mirror in the 0.5 to 100 keV energy band. Composed of two detectors, it will measure the position, energy, and arrival time of each incoming X-ray. On top of it will be a collimator to shield all photons not coming from the mirror field of view. The whole system is surrounded by an active and passive shielding in order to ensure the required very low background.

  11. Focal inflammatory diseases of the liver

    International Nuclear Information System (INIS)

    Oto, Aytekin; Akhan, Okan; Oezmen, Mustafa

    1999-01-01

    Inflammatory lesions constitute an important subgroup of focal liver lesions. They may mimic primary or metastatic neoplastic lesions and their differentiation from neoplasia is clinically very important since management of the patient significantly changes. Radiologists should have an important role in both the diagnosis and therapy of these lesions by performing percutaneous aspirations and drainages. In this review we discussed the radiological findings of pyogenic abscesses, amebic abscesses, candidiasis, tuberculosis, hydatic cysts, fascioliasis, ascariasis, schistosomiasis, and sarcoidosis with a special emphasis on US, CT and MR characteristics

  12. Focal inflammatory diseases of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Oto, Aytekin; Akhan, Okan; Oezmen, Mustafa

    1999-10-01

    Inflammatory lesions constitute an important subgroup of focal liver lesions. They may mimic primary or metastatic neoplastic lesions and their differentiation from neoplasia is clinically very important since management of the patient significantly changes. Radiologists should have an important role in both the diagnosis and therapy of these lesions by performing percutaneous aspirations and drainages. In this review we discussed the radiological findings of pyogenic abscesses, amebic abscesses, candidiasis, tuberculosis, hydatic cysts, fascioliasis, ascariasis, schistosomiasis, and sarcoidosis with a special emphasis on US, CT and MR characteristics.

  13. Characterization of DECam focal plane detectors

    Energy Technology Data Exchange (ETDEWEB)

    Diehl, H.Thomas; Angstadt, Robert; Campa, Julia; Cease, Herman; Derylo, Greg; Emes, John H.; Estrada, Juan; Kibik, Donna; Flaugher, Brenna L.; Holland, Steve E.; Jonas, Michelle; /Fermilab /Madrid, CIEMAT /LBL, Berkeley /Argonne /Pennsylvania U.

    2008-06-01

    DECam is a 520 Mpix, 3 square-deg FOV imager being built for the Blanco 4m Telescope at CTIO. This facility instrument will be used for the 'Dark Energy Survey' of the southern galactic cap. DECam has chosen 250 ?m thick CCDs, developed at LBNL, with good QE in the near IR for the focal plane. In this work we present the characterization of these detectors done by the DES team, and compare it to the DECam technical requirements. The results demonstrate that the detectors satisfy the needs for instrument.

  14. Idiopathic focal epilepsies: the "lost tribe".

    Science.gov (United States)

    Pal, Deb K; Ferrie, Colin; Addis, Laura; Akiyama, Tomoyuki; Capovilla, Giuseppe; Caraballo, Roberto; de Saint-Martin, Anne; Fejerman, Natalio; Guerrini, Renzo; Hamandi, Khalid; Helbig, Ingo; Ioannides, Andreas A; Kobayashi, Katsuhiro; Lal, Dennis; Lesca, Gaetan; Muhle, Hiltrud; Neubauer, Bernd A; Pisano, Tiziana; Rudolf, Gabrielle; Seegmuller, Caroline; Shibata, Takashi; Smith, Anna; Striano, Pasquale; Strug, Lisa J; Szepetowski, Pierre; Valeta, Thalia; Yoshinaga, Harumi; Koutroumanidis, Michalis

    2016-09-01

    The term idiopathic focal epilepsies of childhood (IFE) is not formally recognised by the ILAE in its 2010 revision (Berg et al., 2010), nor are its members and boundaries precisely delineated. The IFEs are amongst the most commonly encountered epilepsy syndromes affecting children. They are fascinating disorders that hold many "treats" for both clinicians and researchers. For example, the IFEs pose many of the most interesting questions central to epileptology: how are functional brain networks involved in the manifestation of epilepsy? What are the shared mechanisms of comorbidity between epilepsy and neurodevelopmental disorders? How do focal EEG discharges impact cognitive functioning? What explains the age-related expression of these syndromes? Why are EEG discharges and seizures so tightly locked to slow-wave sleep? In the last few decades, the clinical symptomatology and the respective courses of many IFEs have been described, although they are still not widely appreciated beyond the specialist community. Most neurologists would recognise the core syndromes of IFE to comprise: benign epilepsy of childhood with centro-temporal spikes or Rolandic epilepsy (BECTS/RE); Panayiotopoulos syndrome; and the idiopathic occipital epilepsies (Gastaut and photosensitive types). The Landau-Kleffner syndrome and the related (idiopathic) epilepsy with continuous spikes and waves in sleep (CSWS or ESES) are also often included, both as a consequence of the shared morphology of the interictal discharges and their potential evolution from core syndromes, for example, CSWS from BECTS. Atypical benign focal epilepsy of childhood also has shared electro-clinical features warranting inclusion. In addition, a number of less well-defined syndromes of IFE have been proposed, including benign childhood seizures with affective symptoms, benign childhood epilepsy with parietal spikes, benign childhood seizures with frontal or midline spikes, and benign focal seizures of adolescence. The

  15. Laparoscopic Partial Hepatectomy of Focal Nodular Hyperplasia

    Directory of Open Access Journals (Sweden)

    Mayu Sakata

    2012-11-01

    Full Text Available Focal nodular hyperplasia is a benign liver lesion incidentally discovered with increasing frequency because of the proliferation of imaging studies. Radiographic characterization can diagnose this pathologic lesion and nonoperative therapy is the standard of care. However, surgical resection may be required for diagnostic reasons or symptomatic patients. Depending on the anatomic location of the lesion, biopsy and/or resection can be performed laparoscopically. We herein report the case of a 26-year-old Japanese woman with a hepatic tumor who required a medical examination. Her medical history was negative for alcohol abuse, oral contraceptive administration and trauma. Clinical examination showed no significant symptoms. Ultrasonography, computed tomography and magnetic resonance imaging showed a mass located in the left lateral segment of the liver with a diameter of about 40 mm. It was difficult to diagnose the tumor definitively from these imaging studies, so we performed laparoscopic partial hepatectomy with successive firing of endoscopic staplers. The histopathological diagnosis was focal nodular hyperplasia. Surgical procedures and postoperative course were uneventful and the patient was discharged from the hospital on postoperative day 5.

  16. CT scan findings in focal epilepsy

    International Nuclear Information System (INIS)

    Kobayashi, Eiki; Mihara, Tadahiro; Yamamoto, Kunimitsu; Yamashita, Kenji; Asakura, Tetsuhiko

    1980-01-01

    In 80 cases of focal epilepsy, excluding such cases as late onset after the age of 30 and traumatic or expansive lesions, the epileptogenic foci have been studied by comparing the CT findings with the seizure types and the EEG findings. The results were as follows: (1) Abnormal CT findings were observed in 36% of the patients. (2) These findings were classified into 4 large groups: localized cerebral atrophy, localized low density, localized high density with contrast enhancement and diffuse cerebral atrophy. (3) The incidence of CT abnormality was higher in the cases with continuous and localized EEG abnormality than in the cases with other types of EEG abnormality. In 48% of the cases, the location of the abnormal CT findings coincided with their EEG foci. (4) In the cases of temporal lobe epilepsy without abnormal CT images, the print-out data compared with the bilateral promised temporal regions, before and after contrast enhancement. The EMI-No. of the medial temporal focus increased more than that of the contralateral side in 3 cases out of 4 after contrast-media injection. (5) Moreover, for the purpose of comparing the CT findings on general seizures with those in focal seizures, we have studied 80 cases of general seizures. In the cases of the general seizures, abnormal CT findings were observed in only 16%. These abnormal findings were diffuse in 5 cases, localized in 6 cases, and combined in 3 cases. (author)

  17. The Sentinel-4 UVN focal plane assemblies

    Science.gov (United States)

    Hinger, Jürgen; Hohn, Rüdiger; Gebhardt, Eyk; Reichardt, Jörg

    2017-09-01

    The Sentinel-4 UVN Instrument is a dispersive imaging spectrometer covering the UV-VIS and the NIR wavelength. It is developed and built under an ESA contract by an industrial consortium led by Airbus Defence and Space. It will be accommodated on board of the MTG-S (Meteosat Third Generation - Sounder) satellite that will be placed in a geostationary orbit over Europe sampling data for generating two-dimensional maps of a number of atmospheric trace gases. The incoming light is dispersed by reflective gratings and detected by the two (UVVIS and NIR) CCDs mounted inside the focal plane assemblies. Both CCD detectors acquire spectral channels and spatial sampling in two orthogonal directions and will be operated at about 215 K mainly to minimize random telegraph signal effects and to reduce dark current. Stringent detector temperature as well as alignment stability requirements of less than +/-0.1 K per day respectively of less than 2 micrometers/2 arcseconds from ground to orbit are driving the FPA thermo-mechanical design. A specific FPA design feature is the redundant LED-calibration system for bad pixel detection as well as pixel gain and linearity monitoring. This paper reports on the design and qualification of the Focal Plane Assemblies with emphasis on thermo-mechanical as well as alignment stability verification.

  18. The Sentinel 4 focal plane subsystem

    Science.gov (United States)

    Hohn, Rüdiger; Skegg, Michael P.; Hermsen, Markus; Hinger, Jürgen; Williges, Christian; Reulke, Ralf

    2017-09-01

    The Sentinel 4 instrument is an imaging spectrometer, developed by Airbus under ESA contract in the frame of the joint European Union (EU)/ESA COPERNICUS program with the objective of monitoring trace gas concentrations. Sentinel 4 will provide accurate measurements of key atmospheric constituents such as ozone, nitrogen dioxide, sulfur dioxide, formaldehyde, as well as aerosol and cloud properties. Sentinel 4 is unique in being the first geostationary UVN mission. The SENTINEL 4 space segment will be integrated on EUMETSAT's Meteosat Third Generation Sounder satellite (MTG-S). Sentinel 4 will provide coverage of Europe and adjacent regions. The Sentinel 4 instrument comprises as a major element two Focal Plane Subsystems (FPS) covering the wavelength ranges 305 nm to 500 nm (UVVIS) and 750 nm to 775 nm (NIR) respectively. The paper describes the Focal Plane Subsystems, comprising the detectors, the optical bench and the control electronics. Further the design and development approach will be presented as well as first measurement results of FPS Qualification Model.

  19. Focal CT abnormality and epileptogenic focus

    International Nuclear Information System (INIS)

    Yagi, Kazuichi; Mihara, Tadahiro; Tottori, Takayasu; Matsuda, Kazumi; Watanabe, Yutaka; Seino, Masakazu

    1989-01-01

    In 31 patients with temporal lobe epilepsy, the precise site of epileptogenic focus was determined by means of a depth EEG recording as one of the presurgical evaluations. In 13 patients, a CT scan revealed focal lesions; 7 in the left temporal lobe and 6 in the right temporal lobe. In 5 of the 7 patients and in 5 of the 6 patients the epileptogenic foci were determined in the temporal lobe on the side of a CT lesion. However, in 2 of the patients with a CT lesion in the left temporal lobe, independent epileptogenic foci were found in both the temporal lobes, and in the other patient with a CT lesion in the right temporal lobe, they were found in the right frontal and left temporal lobes. Thus, the CT lesions agreed in lateralization and focality with the epileptogenic foci in 10 of the 13 patients (77%), but they disagreed in 3 (23%). A CT lesion disclosed in the temporal lobe does not necessarily indicate the side and/or site where the epileptogenic focus may be localized. Although exceptions may be made, spatial disagreement was exemplified between the CT lesion and epileptogenic focus. Therefore, extreme caution has to be taken on the side and/or site of the epileptogenic focus when functional surgical indication is to be made. (author)

  20. Structural and effective connectivity in focal epilepsy

    Directory of Open Access Journals (Sweden)

    Christopher S. Parker

    2018-01-01

    Full Text Available Patients with medically-refractory focal epilepsy may be candidates for neurosurgery and some may require placement of intracranial EEG electrodes to localise seizure onset. Assessing cerebral responses to single pulse electrical stimulation (SPES may give diagnostically useful data. SPES produces cortico-cortical evoked potentials (CCEPs, which infer effective brain connectivity. Diffusion-weighted images and tractography may be used to estimate structural brain connectivity. This combination provides the opportunity to observe seizure onset and its propagation throughout the brain, spreading contiguously along the cortex explored with electrodes, or non-contiguously. We analysed CCEPs and diffusion tractography in seven focal epilepsy patients and reconstructed the effective and structural brain networks. We aimed to assess the inter-modal similarity of the networks at a large scale across the cortex, the effective and structural connectivity of the ictal-onset zone, and investigate potential mechanisms of non-contiguous seizure spread. We found a significant overlap between structural and effective networks. Effective network CCEP amplitude, baseline variation, and outward connectivity was higher at ictal-onset zones, while structural connection strength within the ictal-onset zone tended to be higher. These findings support the concept of hyperexcitable cortex being associated with seizure generation. The high prevalence of structural and effective connections from the ictal-onset zone to sites of non-contiguous spread suggests that macroscopic structural and effective connections are plausible routes for non-contiguous seizure spread.

  1. Ultrasound elastographic techniques in focal liver lesions.

    Science.gov (United States)

    Conti, Clara Benedetta; Cavalcoli, Federica; Fraquelli, Mirella; Conte, Dario; Massironi, Sara

    2016-03-07

    Elastographic techniques are new ultrasound-based imaging techniques developed to estimate tissue deformability/stiffness. Several ultrasound elastographic approaches have been developed, such as static elastography, transient elastography and acoustic radiation force imaging methods, which include point shear wave and shear wave imaging elastography. The application of these methods in clinical practice aims at estimating the mechanical tissues properties. One of the main settings for the application of these tools has been liver stiffness assessment in chronic liver disease, which has been studied mainly using transient elastography. Another field of application for these techniques is the assessment of focal lesions, detected by ultrasound in organs such as pancreas, prostate, breast, thyroid, lymph nodes. Considering the frequency and importance of the detection of focal liver lesions through routine ultrasound, some studies have also aimed to assess the role that elestography can play in studying the stiffness of different types of liver lesions, in order to predict their nature and thus offer valuable non-invasive methods for the diagnosis of liver masses.

  2. Focal fatty infiltra- tion and focal fatty sparing of the liver

    African Journals Online (AJOL)

    Enrique

    Department of Radiology. Nelson Mandela School of Health Sciences. Durban. Fig. 1a. Unenhanced CT of the liver in case 1 demonstrates multiple focal low density regions in both lobes of the liver. Region of interest 1 over the fatty left lobe measured 10 HU while region of interest 2 over the right lobe measure 40 HU in.

  3. CT appearance of focal fatty infiltration of the liver

    International Nuclear Information System (INIS)

    Halvorsen, R.A.; Korobkin, M.; Ram, P.C.; Thompson, W.M.

    1982-01-01

    Focal fatty infiltration of the liver is an entity that may be confused with liver metastasis on computed tomography (CT). The imaging results and medical records of 16 patients with CT appearance suggestive of focal fatty liver were reviewed, three of whom had the simultaneous presence of metastitic liver disease. Focal fatty liver often has a distinctive appearance with CT, usually with a nonspherical shape, absence of mass effect, and density close to water. Liver metastases are usually round or oval, and unless cystic or necrotic, they have CT attenuation values closer to normal liver parenchyma than water. A radionuclide liver scan almost always resolves any confusion about the differential diagnosis of focal fatty liver: a well defined focus of photon deficiency is due to neoplasm rather than focal fatty infiltration. Sonography sometimes helps to confirm the CT impression, but may be misleading if the diagnosis of focal or diffuse fatty infiltration is not suspected before the examination

  4. The study of the focal trough in panoramic radiograph

    International Nuclear Information System (INIS)

    Park, C. S.; Kim, H. P.

    1982-01-01

    In the study of the focal trough of panoramic radiograph, using the Moritta company Panex EC a series of 48 exposures were taken with the 6-18 brass pins placed in the holes of the plastic model plate, then evaluated by 4 observers. The author analyzed the focal trough defined by the sharpness criteria and calculated the vertical and horizontal magnification range in the corrected focal trough. The results were as follows; 1. Continuous focal trough was not defined in the anterior region using a very high degree of sharpness. 2. As degree of sharpness used in the analysis became less, focal trough was continuous in the anterior and posterior regions, symmetrized bilaterally, and the widths of the focal trough increased more in the posterior region. 3. As sharpness criteria were reduced, the percentage range of image magnification increased in both vertical and horizontal magnification, and especially the percentage range of horizontal magnification was greater than that of vertical magnification.

  5. Multi-focal Vision and Gaze Control Improve Navigation Performance

    Directory of Open Access Journals (Sweden)

    Kolja Kuehnlenz

    2008-11-01

    Full Text Available Multi-focal vision systems comprise cameras with various fields of view and measurement accuracies. This article presents a multi-focal approach to localization and mapping of mobile robots with active vision. An implementation of the novel concept is done considering a humanoid robot navigation scenario where the robot is visually guided through a structured environment with several landmarks. Various embodiments of multi-focal vision systems are investigated and the impact on navigation performance is evaluated in comparison to a conventional mono-focal stereo set-up. The comparative studies clearly show the benefits of multi-focal vision for mobile robot navigation: flexibility to assign the different available sensors optimally in each situation, enhancement of the visible field, higher localization accuracy, and, thus, better task performance, i.e. path following behavior of the mobile robot. It is shown that multi-focal vision may strongly improve navigation performance.

  6. Focal cemento-osseous dysplasia of mandible.

    Science.gov (United States)

    Cankaya, Abdülkadir Burak; Erdem, Mehmet Ali; Olgac, Vakur; Firat, Deniz Refia

    2012-09-03

    Fibro-osseous lesions are disturbances in bone metabolism in which normal bone is replaced by a connective tissue matrix that then gradually develops into cemento-osseous tissue. Typically, the lesion is asymptomatic and is detected on routine radiographic examination. Radiologically, this lesion has three stages of maturation: pure radiolucent, radiopaque/mixed radiolucent, and radiopaque appearance. During these stages the lesion can be misdiagnosed. In this case report a 69-year- old patient with a a complaint of painless swelling of the left mandibular molar and premolar area is presented along with a review of the differential diagnoses considered in order to reach a final diagnosis of focal cemento-osseous dysplasia.

  7. Strong reducing of the laser focal volume

    CSIR Research Space (South Africa)

    Godin, T

    2011-08-01

    Full Text Available equal to -1 or +1 modeled on the p light rings of the incident TEMp0 beam. The transformation quality of a 30TEM beam into a single-lobed pattern in the focal plane is shown in Fig. 3. It is clear that the intensity pattern of the rectified beam... DOE (blue solid line), rectified 30TEM (red solid line) -3 -2 -1 0 1 2 3 0 1 2 3 4 z=0 z=f DOE Fig. 2 -60 -50 -40 -30 -20 -10 0 10 20 30 40 50 60 0,0 0,2 0,4 0,6 0,8 1,0 TEM30 without DOE "rectified" TEM30 TEM00 In te ns...

  8. Smart trigger logic for focal plane arrays

    Science.gov (United States)

    Levy, James E; Campbell, David V; Holmes, Michael L; Lovejoy, Robert; Wojciechowski, Kenneth; Kay, Randolph R; Cavanaugh, William S; Gurrieri, Thomas M

    2014-03-25

    An electronic device includes a memory configured to receive data representing light intensity values from pixels in a focal plane array and a processor that analyzes the received data to determine which light values correspond to triggered pixels, where the triggered pixels are those pixels that meet a predefined set of criteria, and determines, for each triggered pixel, a set of neighbor pixels for which light intensity values are to be stored. The electronic device also includes a buffer that temporarily stores light intensity values for at least one previously processed row of pixels, so that when a triggered pixel is identified in a current row, light intensity values for the neighbor pixels in the previously processed row and for the triggered pixel are persistently stored, as well as a data transmitter that transmits the persistently stored light intensity values for the triggered and neighbor pixels to a data receiver.

  9. Pharmacological response of systemically derived focal epileptic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Remler, M.P.; Sigvardt, K.; Marcussen, W.H.

    1986-11-01

    Focal epileptic lesions were made in rats by systemic focal epileptogenesis. In this method, a focal lesion of the blood-brain barrier (BBB) is produced by focal alpha irradiation followed by repeated systemic injection of a convulsant drug that cannot cross the normal BBB, resulting in a chronic epileptic focus. Changes in the spike frequency of these foci in response to various drugs was recorded. The controls, saline and chlorpromazine, produced no change. Phenytoin, phenobarbital, chlordiazepoxide, and valproic acid produced the expected decrease in spike frequency. Pentobarbital and diazepam produced a paradoxical increase in spike frequency.

  10. Metalloproteinase Inhibition Protects against Reductions in Circulating Adrenomedullin during Lead-induced Acute Hypertension.

    Science.gov (United States)

    Nascimento, Regina A; Mendes, Gabryella; Possomato-Vieira, Jose S; Gonçalves-Rizzi, Victor Hugo; Kushima, Hélio; Delella, Flavia K; Dias-Junior, Carlos A

    2015-06-01

    Intoxication with lead (Pb) results in increased blood pressure by mechanisms involving matrix metalloproteinases (MMPs). Recent findings have revealed that MMP type two (MMP-2) seems to cleave vasoactive peptides. This study examined whether MMP-2 and MMP-9 levels/activities increase after acute intoxication with low lead concentrations and whether these changes were associated with increases in blood pressure and circulating endothelin-1 or with reductions in circulating adrenomedullin and calcitonin gene-related peptide (CGRP). Here, we expand previous findings and examine whether doxycycline (a MMPs inhibitor) affects these alterations. Wistar rats received intraperitoneally (i.p.) 1st dose 8 μg/100 g of lead (or sodium) acetate, a subsequent dose of 0.1 μg/100 g to cover daily loss and treatment with doxycycline (30 mg/kg/day) or water by gavage for 7 days. Similar whole-blood lead levels (9 μg/dL) were found in lead-exposed rats treated with either doxycycline or water. Lead-induced increases in systolic blood pressure (from 143 ± 2 to 167 ± 3 mmHg) and gelatin zymography of plasma samples showed that lead increased MMP-9 (but not MMP-2) levels. Both lead-induced increased MMP-9 activity and hypertension were blunted by doxycycline. Doxycycline also prevented lead-induced reductions in circulating adrenomedullin. No significant changes in plasma levels of endothelin-1 or CGRP were found. Lead-induced decreases in nitric oxide markers and antioxidant status were not prevented by doxycycline. In conclusion, acute lead exposure increases blood pressure and MMP-9 activity, which were blunted by doxycycline. These findings suggest that MMP-9 may contribute with lead-induced hypertension by cleaving the vasodilatory peptide adrenomedullin, thereby inhibiting adrenomedullin-dependent lowering of blood pressure. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  11. Sensitivity of stress inversion of focal mechanisms to pore pressure changes

    Czech Academy of Sciences Publication Activity Database

    Martínez-Garzón, P.; Vavryčuk, Václav; Kwiatek, G.; Bohnhoff, M.

    2016-01-01

    Roč. 43, č. 16 (2016), s. 8441-8450 ISSN 0094-8276 R&D Projects: GA ČR(CZ) GAP210/12/1491; GA ČR(CZ) GC16-19751J Institutional support: RVO:67985530 Keywords : fault ing regime * fluid-induced seismicity * focal mechanisms Subject RIV: DC - Siesmology, Volcanology, Earth Structure Impact factor: 4.253, year: 2016

  12. Synchronous inhibitory potentials precede seizure-like events in acute models of focal limbic seizures.

    Science.gov (United States)

    Uva, Laura; Breschi, Gian Luca; Gnatkovsky, Vadym; Taverna, Stefano; de Curtis, Marco

    2015-02-18

    Interictal spikes in models of focal seizures and epilepsies are sustained by the synchronous activation of glutamatergic and GABAergic networks. The nature of population spikes associated with seizure initiation (pre-ictal spikes; PSs) is still undetermined. We analyzed the networks involved in the generation of both interictal and PSs in acute models of limbic cortex ictogenesis induced by pharmacological manipulations. Simultaneous extracellular and intracellular recordings from both principal cells and interneurons were performed in the medial entorhinal cortex of the in vitro isolated guinea pig brain during focal interictal and ictal discharges induced in the limbic network by intracortical and brief arterial infusions of either bicuculline methiodide (BMI) or 4-aminopyridine (4AP). Local application of BMI in the entorhinal cortex did not induce seizure-like events (SLEs), but did generate periodic interictal spikes sensitive to the glutamatergic non-NMDA receptor antagonist DNQX. Unlike local applications, arterial perfusion of either BMI or 4AP induced focal limbic SLEs. PSs just ahead of SLE were associated with hyperpolarizing potentials coupled with a complete blockade of firing in principal cells and burst discharges in putative interneurons. Interictal population spikes recorded from principal neurons between two SLEs correlated with a depolarizing potential. We demonstrate in two models of acute limbic SLE that PS events are different from interictal spikes and are sustained by synchronous activation of inhibitory networks. Our findings support a prominent role of synchronous network inhibition in the initiation of a focal seizure. Copyright © 2015 the authors 0270-6474/15/353048-08$15.00/0.

  13. Sighting optics including an optical element having a first focal length and a second focal length and methods for sighting

    Science.gov (United States)

    Crandall, David Lynn

    2011-08-16

    Sighting optics include a front sight and a rear sight positioned in a spaced-apart relation. The rear sight includes an optical element having a first focal length and a second focal length. The first focal length is selected so that it is about equal to a distance separating the optical element and the front sight and the second focal length is selected so that it is about equal to a target distance. The optical element thus brings into simultaneous focus for a user images of the front sight and the target.

  14. Expression of Neurotrophin-3 and trkC following Focal Cerebral Ischemia in Adult Rat Brain with Treadmill Exercise

    Directory of Open Access Journals (Sweden)

    Jin-Young Chung

    2017-01-01

    Full Text Available Neurotrophin-3 (NT-3 is a neurotrophic factor that mainly binds to the tyrosine kinase C (trkC receptor. NT-3 has been shown to have neuroprotective effects in focal cerebral ischemia. Exercise also has ability to induce functional recovery in focal cerebral ischemia. However, the relationship between NT-3, its receptor trkC, and exercise has not been revealed. In this study, we assessed the expressions of NT-3 and trkC in focal cerebral ischemia. We also assessed the expression of NT-3 and trkC with treadmill exercise in focal cerebral ischemia. The results showed that, in a permanent middle cerebral artery occlusion rat model, exercise increased NT-3 and trkC expression. However, the patterns of expression of NT-3 and trkC at different time points varied. These results suggest that exercise-induced functional recovery in focal cerebral ischemia was related to NT-3 and trkC, but the role on times of NT-3 and trkC differed, although trkC is the receptor kinase for NT-3.

  15. Radiologic manifestations of focal cerebral hyperemia in acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj; Skriver, E B; Herning, M

    1991-01-01

    In 16 acute stroke patients with focal cerebral hyperemia angiography and regional cerebral blood flow (rCBF) were studied 1 to 4 days post stroke. CT was performed twice with and without contrast enhancement 3 +/- 1 days and 16 +/- 4 days post stroke. Angiographic evidence of focal cerebral hype...

  16. Focal decompositions for linear differential equations of the second order

    Directory of Open Access Journals (Sweden)

    L. Birbrair

    2003-01-01

    two-points problems to itself such that the image of the focal decomposition associated to the first equation is a focal decomposition associated to the second one. In this paper, we present a complete classification for linear second-order equations with respect to this equivalence relation.

  17. Focal necrotizing pneumonia is a distinct entity from lung abscess.

    Science.gov (United States)

    Seo, Hyewon; Cha, Seung-Ick; Shin, Kyung-Min; Lim, Jaekwang; Yoo, Seung-Soo; Lee, Jaehee; Lee, Shin-Yup; Kim, Chang-Ho; Park, Jae-Yong

    2013-10-01

    'Focal necrotizing pneumonia' was defined as a localized type of necrotizing pneumonia characterized by a single or few cavities of low density without rim enhancement on computed tomography (CT) scan. The purpose of this study was to investigate the clinical features and course of patients with focal necrotizing pneumonia, thereby elucidating its clinical relevance. The present study was conducted retrospectively in patients who had been interpreted as having lung abscess or necrotizing pneumonia on CT scan. Clinical and radiological characteristics were compared between the focal necrotizing pneumonia and lung abscess groups. Overall, 68 patients with focal necrotizing pneumonia (n = 35) or lung abscess (n = 33) were included in the present study. The frequency of risk factors for aspiration was significantly lower in the focal necrotizing group, compared with the lung abscess group (14.3% vs 45.5%, P = 0.005). Compared with lung abscess, focal necrotizing pneumonia was observed more commonly in non-gravity-dependent segments (66% vs 36%, P lung abscess group (31% vs 12%, P = 0.08). However, in terms of treatment outcomes, a similar high rate of success was observed in both groups: 97%, respectively. Compared to lung abscess, focal necrotizing pneumonia occurs more commonly in non-gravity-dependent segments with lower incidence of risk factors for aspiration. Similar to lung abscess, the rate of success for treatment of focal necrotizing pneumonia was high. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

  18. Proximal Focal Femoral Deficiency in Ibadan a Developing ...

    African Journals Online (AJOL)

    The cultural aversion to amputation in our environment makes it difficult to employ that option of treatment. Proximal focal femoral deficiency in Ibadan a developing country's perspective and a review of the literature. Keywords: Proximal focal femoral deficiency , congenital malformations , limb malformations , lower limb ...

  19. Concordance of MRI and EEG Focal Slowing in Nonsyndromic Epilepsy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-04-01

    Full Text Available Investigators at the Kangwon National University, Korea, and The Epilepsy Center, Lurie Children’s Hospital of Chicago, USA studied the correlation and significance of EEG focal slowing and focal MRI abnormalities in 253 children with nonsyndromic epilepsy.

  20. An empirical assessment of the focal species hypothesis.

    Science.gov (United States)

    Lindenmayer, D B; Lane, P W; Westgate, M J; Crane, M; Michael, D; Okada, S; Barton, P S

    2014-12-01

    Biodiversity surrogates and indicators are commonly used in conservation management. The focal species approach (FSA) is one method for identifying biodiversity surrogates, and it is underpinned by the hypothesis that management aimed at a particular focal species will confer protection on co-occurring species. This concept has been the subject of much debate, in part because the validity of the FSA has not been subject to detailed empirical assessment of the extent to which a given focal species actually co-occurs with other species in an assemblage. To address this knowledge gap, we used large-scale, long-term data sets of temperate woodland birds to select focal species associated with threatening processes such as habitat isolation and loss of key vegetation attributes. We quantified co-occurrence patterns among focal species, species in the wider bird assemblage, and species of conservation concern. Some, but not all, focal species were associated with high levels of species richness. One of our selected focal species was negatively associated with the occurrence of other species (i.e., it was an antisurrogate)-a previously undescribed property of nominated focal species. Furthermore, combinations of focal species were not associated with substantially elevated levels of bird species richness, relative to levels associated with individual species. Our results suggest that although there is some merit to the underpinning concept of the FSA, there is also a need to ensure that actions are sufficiently flexible because management tightly focused on a given focal species may not benefit some other species, including species of conservation concern, such of which might not occur in species-rich assemblages. © 2014 Society for Conservation Biology.

  1. [Sotos syndrome associated with focal dystonia].

    Science.gov (United States)

    Bravo, M; Chacón, J; Bautista, E; Pérez-Camacho, I; Trujillo, A; Grande, M A

    Sotos syndrome is a form of infantile gigantism characterized by excessive body size from the time of birth, particular facies, acromegalic changes and signs of non-progressive cerebral involvement. The etiology is unknown. Diagnosis is based on somatometric data and the particular phenotype traits. Biochemical and endocrine studies are normal. Torticollis is a focal dystonia and therefore more common in adults. A 20 year old woman with macrosomic features since birth presented with: weight 104 kg, height 182 cm; prognathism, hypertelorism, a broad over hanging forehead with a high hair line; large ears, hands and feet; torticollis towards the right with elevation and anteroversion of the right shoulder which caused symptomatic scoliosis. She was bradypsychic and rather slow in speech. The complementary tests done (cerebral and cervical CT and MR, bone gammography, evoked potentials, EMG-ENG, sural nerve biopsy, biopsy of skin and muscle, EEG and hormone and biochemistry studies) were normal. The torticollis was treated with botulinus toxin and improved considerably, as did the scoliosis. To date, dystonia has not been described in association with Sotos syndrome. This may be a causal association, or even perhaps hereditary, since the patient's mother had dystonia (in the form of blepharospasm).

  2. Depression in focal, segmental and generalized dystonia.

    Science.gov (United States)

    Lewis, L; Butler, A; Jahanshahi, M

    2008-11-01

    Dystonia causes body disfigurement in the majority of those affected. Our aim was to test the hypothesis that low self-esteem resulting from the sense of disfigurement is an important component of self-reported depression in focal, segmental and generalized dystonia. Questionnaires to assess self-reported depression, self-esteem, body concept, disfigurement, disability and quality of life were completed by 329 community based dystonia patients. Moderate to severe depression was reported by 30 %. Self-reported depression had a strong somatic component, but patients also showed a specific concern with self-image. Extent of dystonia, body parts affected and marital status influenced self-reported depression in dystonia. Self esteem, body concept, disfigurement and quality of life emerged as factors which accounted for the variance of self-reported depression in dystonia. These results suggest that in dystonia, disfigurement, negative body concept, low self-esteem, and the impact of the disease on quality of life make important contributions to depression. However, longitudinal followup is required to firmly establish the direction of causality between depression and these psychosocial variables in dystonia.

  3. Visual agnosia and focal brain injury.

    Science.gov (United States)

    Martinaud, O

    Visual agnosia encompasses all disorders of visual recognition within a selective visual modality not due to an impairment of elementary visual processing or other cognitive deficit. Based on a sequential dichotomy between the perceptual and memory systems, two different categories of visual object agnosia are usually considered: 'apperceptive agnosia' and 'associative agnosia'. Impaired visual recognition within a single category of stimuli is also reported in: (i) visual object agnosia of the ventral pathway, such as prosopagnosia (for faces), pure alexia (for words), or topographagnosia (for landmarks); (ii) visual spatial agnosia of the dorsal pathway, such as cerebral akinetopsia (for movement), or orientation agnosia (for the placement of objects in space). Focal brain injuries provide a unique opportunity to better understand regional brain function, particularly with the use of effective statistical approaches such as voxel-based lesion-symptom mapping (VLSM). The aim of the present work was twofold: (i) to review the various agnosia categories according to the traditional visual dual-pathway model; and (ii) to better assess the anatomical network underlying visual recognition through lesion-mapping studies correlating neuroanatomical and clinical outcomes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Evaluation of Hemodynamics in Focal Steatosis and Focal Spared Lesion of the Liver Using Contrast-Enhanced Ultrasonography with Sonazoid

    International Nuclear Information System (INIS)

    Shiozawa, K.; Watanabe, M.; Ikehara, T.; Kogame, M.; Shinohara, M.; Shinohara, M.; Ishii, K.; Igarashi, Y.; Sumino, Y.; Shiozawa, K.; Makino, H.

    2014-01-01

    We aim to investigate the hemodynamics in focal steatosis and focal spared lesion of the liver using contrast-enhanced ultrasonography (CEUS) with Sonazoid. The subjects were 47 patients with focal steatosis and focal spared lesion. We evaluated enhancement patterns (hyper enhancement, iso enhancement, and hypo enhancement) in the vascular phase and the presence or absence of a hypoechoic area in the post vascular phase for these lesions using CEUS. Of the 24 patients with focal steatosis, the enhancement pattern was iso enhancement in 19 and hypo enhancement in 5. Hypoechoic areas were noted in the post vascular phase in 3 patients. Of the 23 patients with focal spared lesions, the enhancement pattern was iso enhancement in 18 and hyper enhancement in 5. No hypoechoic areas were noted in the post vascular phase in any patient. The hemodynamics in focal steatosis and focal spared lesions in non diffuse fatty liver can be observed using low-invasive procedures in real-time by CEUS. It was suggested that differences in the dynamics of enhancement in the vascular phase of CEUS were influenced by the fat deposits in the target lesion, the surrounding liver parenchyma, and the third inflow.

  5. MR imaging guidance and monitoring of focal thermotherapies. A review

    International Nuclear Information System (INIS)

    Mueller-Lisse, U.G.; California Univ., San Francisco, CA; Heuck, A.F.

    1998-01-01

    Minimally invasive thermotherapies for focal tissue destruction on the basis of laser-, microwave-, focused ultrasound-, or cryogeninduced changes of tissue temperature represent an alternative to surgical tissue ablation, particularly in the treatment of tumors. The thermotherapy modalities listed necessitate indirect guidance and monitoring, since they often do not lend themselves to immediate visual control. In the brain, in head and neck tumors, in the liver, and in the prostate, MRI reliably and accurately delineates both the positions of interstitial thermotherapy applicators and - in contrast-enhanced, T1-weighted images - the perfusion defects in tissue necrosis induced by thermotherapy. The transfer of results of in-vitro and in-vivo model studies to assess interstitial temperature and lesion development during thermotherapy to the actual treatment of patients, however, is still in an initial phase. Further development of both rapid MRI sequences and MRI scanners suited for interventions will show how far treatment systems and guidance systems can be adapted to one another. (orig.) [de

  6. Antigen-driven focal inflammatory death of malaria liver stages

    Directory of Open Access Journals (Sweden)

    Ganchimeg eBayarsaikhan

    2015-02-01

    Full Text Available Multiple immunizations using live irradiated sporozoites, the infectious plasmodial stage delivered into the host skin during a mosquito bite, can elicit sterile immunity to malaria. CD8+ T cells seem to play an essential role in this protective immunity, since their depletion consistently abolishes sterilizing protection in several experimental models. So far, only a few parasite antigens are known to induce CD8+ T cell-dependent protection, but none of them can reach the levels of protection afforded by live attenuated parasites. Systematic attempts to identify novel antigens associated with this efficient cellular protection were so far unsuccessful. In addition, the precise mechanisms involved in the recognition and elimination of parasitized hepatocytes in vivo by CD8+ T cells still remain obscure. Recently, it has been shown that specific effector CD8+ T cells, after recognition of parasitized hepatocytes, recruit specific and non-specific activated CD8+ T cells to the site of infection, resulting in the formation of cellular clusters around and in the further elimination of intracellular parasites. The significance of this finding is discussed in the perspective of a general mechanism of antigen-dependent focalized inflammation and its consequences for the elimination of malaria liver stages.

  7. Resveratrol prevents high-fructose corn syrup-induced vascular insulin resistance and dysfunction in rats.

    Science.gov (United States)

    Babacanoglu, C; Yildirim, N; Sadi, G; Pektas, M B; Akar, F

    2013-10-01

    Dietary intake of fructose and sucrose can cause development of metabolic and cardiovascular disorders. The consequences of high-fructose corn syrup (HFCS), a commonly consumed form of fructose and glucose, have poorly been examined. Therefore, in this study, we investigated whether HFCS intake (10% and 20% beverages for 12 weeks) impacts vascular reactivity to insulin and endothelin-1 in conjunction with insulin receptor substrate-1(IRS-1), endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) mRNA/proteins levels in aorta of rats. At challenge, we tested the effectiveness of resveratrol (28-30 mg/kg body weight/day) on outcomes of HFCS feeding. HFCS (20%) diet feeding increased plasma triglyceride, VLDL, cholesterol, insulin and glucose levels, but not body weights of rats. Impaired nitric oxide-mediated relaxation to insulin (10⁻⁹ to 3×10⁻⁶ M), and enhanced contraction to endothelin-1 (10⁻¹¹ to 10⁻⁸ M) were associated with decreased expression of IRS-1 and eNOS mRNA and protein, but increased expression of iNOS, in aortas of rats fed with HFCS. Resveratrol supplementation restored many features of HFCS-induced disturbances, probably by regulating eNOS and iNOS production. In conclusion, dietary HFCS causes vascular insulin resistance and endothelial dysfunction through attenuating IRS-1 and eNOS expressions as well as increasing iNOS in rats. Resveratrol has capability to recover HFCS-induced disturbances. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  8. Simulation of a conductive shield plate for the focalization of transcranial magnetic stimulation in the rat.

    Science.gov (United States)

    Gasca, Fernando; Richter, Lars; Schweikard, Achim

    2010-01-01

    Transcranial Magnetic Stimulation (TMS) in the rat is a powerful tool for investigating brain function. However, the state-of-the-art experiments are considerably limited because the stimulation usually affects undesired anatomical structures. A simulation of a conductive shield plate placed between the coil stimulator and the rat brain during TMS is presented. The Finite Element (FE) method is used to obtain the 3D electric field distribution on a four-layer rat head model. The simulations show that the shield plate with a circular window can improve the focalization of stimulation, as quantitatively seen by computing the three-dimensional half power region (HPR). Focalization with the shield plate showed a clear compromise with the attenuation of the induced field. The results suggest that the shield plate can work as a helpful tool for conducting TMS rat experiments on specific targets.

  9. Parietal Epithelial Cells Participate in the Formation of Sclerotic Lesions in Focal Segmental Glomerulosclerosis

    Science.gov (United States)

    Smeets, Bart; Kuppe, Christoph; Sicking, Eva-Maria; Fuss, Astrid; Jirak, Peggy; van Kuppevelt, Toin H.; Endlich, Karlhans; Wetzels, Jack F.M.; Gröne, Hermann-Josef; Floege, Jürgen

    2011-01-01

    The pathogenesis of the development of sclerotic lesions in focal segmental glomerulosclerosis (FSGS) remains unknown. Here, we selectively tagged podocytes or parietal epithelial cells (PECs) to determine whether PECs contribute to sclerosis. In three distinct models of FSGS (5/6-nephrectomy + DOCA-salt; the murine transgenic chronic Thy1.1 model; or the MWF rat) and in human biopsies, the primary injury to induce FSGS associated with focal activation of PECs and the formation of cellular adhesions to the capillary tuft. From this entry site, activated PECs invaded the affected segment of the glomerular tuft and deposited extracellular matrix. Within the affected segment, podocytes were lost and mesangial sclerosis developed within the endocapillary compartment. In conclusion, these results demonstrate that PECs contribute to the development and progression of the sclerotic lesions that define FSGS, but this pathogenesis may be relevant to all etiologies of glomerulosclerosis. PMID:21719782

  10. Rapamycin preconditioning attenuates transient focal cerebral ischemia/reperfusion injury in mice.

    Science.gov (United States)

    Yin, Lele; Ye, Shasha; Chen, Zhen; Zeng, Yaoying

    2012-12-01

    Rapamycin, an mTOR inhibitor and immunosuppressive agent in clinic, has protective effects on traumatic brain injury and neurodegenerative diseases. But, its effects on transient focal ischemia/reperfusion disease are not very clear. In this study, we examined the effects of rapamycin preconditioning on mice treated with middle cerebral artery occlusion/reperfusion operation (MCAO/R). We found that the rapamycin preconditioning by intrahippocampal injection 20 hr before MCAO/R significantly improved the survival rate and longevity of mice. It also decreased the neurological deficit score, infracted areas and brain edema. In addition, rapamycin preconditioning decreased the production of NF-κB, TNF-α, and Bax, but not Bcl-2, an antiapoptotic protein in the ischemic area. From these results, we may conclude that rapamycin preconditioning attenuate transient focal cerebral ischemia/reperfusion injury and inhibits apoptosis induced by MCAO/R in mice.

  11. Inflammation and the neurovascular unit in the setting of focal cerebral ischemia.

    Science.gov (United States)

    del Zoppo, G J

    2009-02-06

    Responses to focal cerebral ischemia by neurons and adjacent microvessels are rapid, simultaneous, and topographically related. Recent observations indicate the simultaneous appearance of proteases by components of nearby microvessels that are also expressed by neurons in the ischemic territory, implying that the events could be coordinated. The structural relationship of neurons to their microvascular supply, the direct functional participation of glial cells, and the observation of a highly ordered microvessel-neuron response to ischemia suggest that these elements are arranged in and behave in a unitary fashion, the neurovascular unit. Their roles as a unit in the stimulation of cellular inflammation and the generation of inflammatory mediators during focal cerebral ischemia have not been explored yet. However, components of the neurovascular unit both generate and respond to these influences under the conditions of ischemia. Here we briefly explore the potential inter-relationships of the components of the neurovascular unit with respect to their potential roles in ischemia-induced inflammatory responses.

  12. Intermittent fasting is neuroprotective in focal cerebral ischemia by minimizing autophagic flux disturbance and inhibiting apoptosis.

    Science.gov (United States)

    Jeong, Ji Heun; Yu, Kwang Sik; Bak, Dong Ho; Lee, Je Hun; Lee, Nam Seob; Jeong, Young Gil; Kim, Dong Kwan; Kim, Jwa-Jin; Han, Seung-Yun

    2016-11-01

    Previous studies have demonstrated that autophagy induced by caloric restriction (CR) is neuroprotective against cerebral ischemia. However, it has not been determined whether intermittent fasting (IF), a variation of CR, can exert autophagy-related neuroprotection against cerebral ischemia. Therefore, the neuroprotective effect of IF was evaluated over the course of two weeks in a rat model of focal cerebral ischemia, which was induced by middle cerebral artery occlusion and reperfusion (MCAO/R). Specifically, the role of autophagy modulation as a potential underlying mechanism for this phenomenon was investigated. It was demonstrated that IF reduced infarct volume and brain edema, improved neurobehavioral deficits, and rescued neuronal loss after MCAO/R. Furthermore, neuronal apoptosis was decreased by IF in the rat cortex. An increase in the number of autophagosomes (APs) was demonstrated in the cortices of IF-treated rats, using immunofluorescence staining and transmission electron microscopy. Using immunoblots, an IF-induced increase was detected in microtubule-associated protein 1 light chain 3 (LC3)-II, Rab7, and cathepsin D protein levels, which corroborated previous morphological studies. Notably, IF reduced the accumulation of APs and p62, demonstrating that IF attenuated the MCAO/R-induced disturbance of autophagic flux in neurons. The findings of the present study suggest that IF-induced neuroprotection in focal cerebral ischemia is due, at least in part, to the minimization of autophagic flux disturbance and inhibition of apoptosis.

  13. Focal Atrichia: A Diagnostic Clue in Female Pattern Hair Loss.

    Science.gov (United States)

    Olsen, Elise A; Whiting, David A

    2017-10-07

    Focal atrichia is a common clinical finding in female pattern hair loss whose specificity and histologic findings need further clarification. To determine the frequency of focal atrichia in various types of hair loss and its histologic characteristics in female pattern hair loss. Part 1: Review of 250 consecutive female patients seen with hair loss for the presence of focal atrichia and Part 2: paired biopsies of haired areas vs focal atrichia in 18 subjects with female pattern hair loss RESULTS: Focal atrichia was seen in 46/104 (44%) of women with female pattern hair loss, including 67% of late onset vs 15% of early onset, compared to 3/146 (2%) of those with other hair disorders Biopsy findings of focal atrichia in female pattern hair loss showed primarily a more progressive miniaturization process than that of haired areas of the scalp. Some women with female pattern hair loss may have had concomitant chronic telogen effluvium CONCLUSIONS: When present, focal atrichia is a clinical clue to the diagnosis of female pattern hair loss, particularly late onset subtype. Copyright © 2017. Published by Elsevier Inc.

  14. The semiology of febrile seizures: Focal features are frequent.

    Science.gov (United States)

    Takasu, Michihiko; Kubota, Tetsuo; Tsuji, Takeshi; Kurahashi, Hirokazu; Numoto, Shingo; Watanabe, Kazuyoshi; Okumura, Akihisa

    2017-08-01

    To clarify the semiology of febrile seizures (FS) and to determine the frequency of FS with symptoms suggestive of focal onset. FS symptoms in children were reported within 24h of seizure onset by the parents using a structured questionnaire consisting principally of closed-ended questions. We focused on events at seizure commencement, including changes in behavior and facial expression, and ocular and oral symptoms. We also investigated the autonomic and motor symptoms developing during seizures. The presence or absence of focal and limbic features was determined for each patient. The associations of certain focal and limbic features with patient characteristics were assessed. Information was obtained on FS in 106 children. Various events were recorded at seizure commencement. Behavioral changes were observed in 35 children, changes in facial expression in 53, ocular symptoms in 78, and oral symptoms in 90. In terms of events during seizures, autonomic symptoms were recognized in 78, and convulsive motor symptoms were recognized in 68 children. Focal features were evident in 81 children; 38 children had two or more such features. Limbic features were observed in 44 children, 9 of whom had two or more such features. There was no significant relationship between any patient characteristic and the numbers of focal or limbic features. The semiology of FS varied widely among children, and symptoms suggestive of focal onset were frequent. FS of focal onset may be more common than is generally thought. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. The dispersion-focalization theory of sound systems

    Science.gov (United States)

    Schwartz, Jean-Luc; Abry, Christian; Boë, Louis-Jean; Vallée, Nathalie; Ménard, Lucie

    2005-04-01

    The Dispersion-Focalization Theory states that sound systems in human languages are shaped by two major perceptual constraints: dispersion driving auditory contrast towards maximal or sufficient values [B. Lindblom, J. Phonetics 18, 135-152 (1990)] and focalization driving auditory spectra towards patterns with close neighboring formants. Dispersion is computed from the sum of the inverse squared inter-spectra distances in the (F1, F2, F3, F4) space, using a non-linear process based on the 3.5 Bark critical distance to estimate F2'. Focalization is based on the idea that close neighboring formants produce vowel spectra with marked peaks, easier to process and memorize in the auditory system. Evidence for increased stability of focal vowels in short-term memory was provided in a discrimination experiment on adult French subjects [J. L. Schwartz and P. Escudier, Speech Comm. 8, 235-259 (1989)]. A reanalysis of infant discrimination data shows that focalization could well be the responsible for recurrent discrimination asymmetries [J. L. Schwartz et al., Speech Comm. (in press)]. Recent data about children vowel production indicate that focalization seems to be part of the perceptual templates driving speech development. The Dispersion-Focalization Theory produces valid predictions for both vowel and consonant systems, in relation with available databases of human languages inventories.

  16. Widespread EEG changes precede focal seizures.

    Directory of Open Access Journals (Sweden)

    Piero Perucca

    Full Text Available The process by which the brain transitions into an epileptic seizure is unknown. In this study, we investigated whether the transition to seizure is associated with changes in brain dynamics detectable in the wideband EEG, and whether differences exist across underlying pathologies. Depth electrode ictal EEG recordings from 40 consecutive patients with pharmacoresistant lesional focal epilepsy were low-pass filtered at 500 Hz and sampled at 2,000 Hz. Predefined EEG sections were selected immediately before (immediate preictal, and 30 seconds before the earliest EEG sign suggestive of seizure activity (baseline. Spectral analysis, visual inspection and discrete wavelet transform were used to detect standard (delta, theta, alpha, beta and gamma and high-frequency bands (ripples and fast ripples. At the group level, each EEG frequency band activity increased significantly from baseline to the immediate preictal section, mostly in a progressive manner and independently of any modification in the state of vigilance. Preictal increases in each frequency band activity were widespread, being observed in the seizure-onset zone and lesional tissue, as well as in remote regions. These changes occurred in all the investigated pathologies (mesial temporal atrophy/sclerosis, local/regional cortical atrophy, and malformations of cortical development, but were more pronounced in mesial temporal atrophy/sclerosis. Our findings indicate that a brain state change with distinctive features, in the form of unidirectional changes across the entire EEG bandwidth, occurs immediately prior to seizure onset. We postulate that these changes might reflect a facilitating state of the brain which enables a susceptible region to generate seizures.

  17. Focal Segmental Glomerulosclerosis: A Single Center Experience

    Directory of Open Access Journals (Sweden)

    Yavuz Ayar

    2016-09-01

    Full Text Available Aim: Focal segmental glomerulosclerosis (FSGS is one of the most common glomerulonephritis (GNP worldwide. Despite treatment, it may progress to end-stage renal disease. In the present study, we compared clinical and histopathological data on FSGS with primary and secondary GNP retrospectively. Methods: We retrospectively analyzed data on clinical and laboratory findings, treatment response, and risk factors associated with mortality in patients, who had been diagnosed with FSGS and other GNP via renal biopsy between January 2009 and December 2014. The average follow-up time was 22 (8-76 months. Results: FSGS and primary GNP were more frequently seen in males than in females (55.9% vs. 65.3%, p=0.033. Nephrotic syndrome was more common in patients with FSGS (41.2% and primary GNP (57.7%, while chronic renal disease was more frequent in patients with secondary GNP (35%. In FSGS, the complete remission rate was 54.4%. 63.2% of patients had continued to receive treatment. According to the biopsy findings, interstitial inflammation and fibrosis were observed in 100% and 98.5% of patients with FSGS, respectively (p=0.010 and p<0.001, respectively. Serum albumin level was found to be increased and proteinuria, total cholesterol, triglyceride, and LDL levels to be decreased after treatment (p<0.001. Serum creatinine levels and type of GNP (secondary GNP were detected to be 1.48 and 8.14 fold increased in mortality analysis, respectively. Conclusion: Renal biopsy is the gold standard for the diagnosis of glomerular diseases. Renal function at the time of diagnosis, follow-up and appropriate immunosuppressive therapy have effects on mortality and clinical progress in FSGS as is the case in all GNPs.

  18. Focal Length Affects Depicted Shape and Perception of Facial Images.

    Directory of Open Access Journals (Sweden)

    Vít Třebický

    Full Text Available Static photographs are currently the most often employed stimuli in research on social perception. The method of photograph acquisition might affect the depicted subject's facial appearance and thus also the impression of such stimuli. An important factor influencing the resulting photograph is focal length, as different focal lengths produce various levels of image distortion. Here we tested whether different focal lengths (50, 85, 105 mm affect depicted shape and perception of female and male faces. We collected three portrait photographs of 45 (22 females, 23 males participants under standardized conditions and camera setting varying only in the focal length. Subsequently, the three photographs from each individual were shown on screen in a randomized order using a 3-alternative forced-choice paradigm. The images were judged for attractiveness, dominance, and femininity/masculinity by 369 raters (193 females, 176 males. Facial width-to-height ratio (fWHR was measured from each photograph and overall facial shape was analysed employing geometric morphometric methods (GMM. Our results showed that photographs taken with 50 mm focal length were rated as significantly less feminine/masculine, attractive, and dominant compared to the images taken with longer focal lengths. Further, shorter focal lengths produced faces with smaller fWHR. Subsequent GMM revealed focal length significantly affected overall facial shape of the photographed subjects. Thus methodology of photograph acquisition, focal length in this case, can significantly affect results of studies using photographic stimuli perhaps due to different levels of perspective distortion that influence shapes and proportions of morphological traits.

  19. The design of LMJ focal spots for indirect drive experiments

    International Nuclear Information System (INIS)

    Le Garrec, B J; Sajer, J M

    2008-01-01

    LMJ is a 240 high power laser beam facility for achieving laser matter interaction experiments, high energy density science, including the demonstration of fusion ignition through Inertial Confinement. The Laser Integration Line (LIL) facility is currently a 4-beam prototype for LMJ. The intensity I 0 at the focal spot centre drives hydrodynamic and plasma instabilities and the intensity in the wings must be low to go through the laser entrance Hohlraum. A simple model has been developed to compute the LMJ focal spot. The model gives the intensity at the centre as a function of the focal spot area at 3% of the maximum

  20. Focal cemento-osseous dysplasia: review and a case report.

    Science.gov (United States)

    Salem, Y M Y; Osman, Y I; Norval, E J G

    2010-10-01

    Focal cemento-osseous dysplasia is a benign fibro-osseous condition that can be seen in dentate and edentulous patients. It is an asymptomatic lesion and needs no treatment; however follow-up is essential due to the possibility that focal cemento-osseous dysplasia can progress to a condition called florid osseous dysplasia that involves multiple sites. A case report is presented here, along with a review of the differential diagnoses considered in order to reach a final diagnosis of focal cemento-osseous dysplasia.

  1. Benign focal liver lesions: discrimination from malignant mimickers.

    Science.gov (United States)

    Alobaidi, Mohammad; Shirkhoda, Ali

    2004-01-01

    Focal lesions of the liver often have various imaging characteristics which may be interpreted as either benign or malignant. Understanding the underlying pathophysiology of these liver lesions may lead to characteristic imaging manifestations, which direct the radiologist to the diagnosis. Benign lesions include congenital hepatic cyst, autosomal dominant polycystic disease, hemangioma, focal nodular hyperplasia (FNH), hepatic adenoma, inflammatory pseudotumor, peliosis hepatis, focal fatty infiltration, hamartoma, and infectious processes such as hepatic abscess, echinococcal cyst, and candidiasis. Characteristic imaging features, clinical symptoms, and treatment/prognosis will be discussed. Emphasis will be placed on key reliable features of each disease to develop a method of discriminating these lesions from other benign and malignant disorders.

  2. Dual-layer electrode-driven liquid crystal lens with electrically tunable focal length and focal plane

    Science.gov (United States)

    Zhang, Y. A.; Lin, C. F.; Lin, J. P.; Zeng, X. Y.; Yan, Q.; Zhou, X. T.; Guo, T. L.

    2018-04-01

    Electric-field-driven liquid crystal (ELC) lens with tunable focal length and their depth of field has been extensively applied in 3D display and imaging systems. In this work, a dual-layer electrode-driven liquid crystal (DELC) lens with electrically tunable focal length and controllable focal plane is demonstrated. ITO-SiO2-AZO electrodes with the dual-layer staggered structure on the top substrate are used as driven electrodes within a LC cell, which permits the establishment of an alternative controllability. The focal length of the DELC lens can be adjusted from 1.41 cm to 0.29 cm when the operating voltage changes from 15 V to 40 V. Furthermore, the focal plane of the DELC lens can selectively move by changing the driving method of the applied voltage to the next driven electrodes. This work demonstrates that the DELC lens has potential applications in imaging systems because of electrically tunable focal length and controllable focal plane.

  3. DEPDC5 takes a second hit in familial focal epilepsy.

    Science.gov (United States)

    Anderson, Matthew P

    2018-04-30

    Loss-of-function mutations in a single allele of the gene encoding DEP domain-containing 5 protein (DEPDC5) are commonly linked to familial focal epilepsy with variable foci; however, a subset of patients presents with focal cortical dysplasia that is proposed to result from a second-hit somatic mutation. In this issue of the JCI, Ribierre and colleagues provide several lines of evidence to support second-hit DEPDC5 mutations in this disorder. Moreover, the authors use in vivo, in utero electroporation combined with CRISPR-Cas9 technology to generate a murine model of the disease that recapitulates human manifestations, including cortical dysplasia-like changes, focal seizures, and sudden unexpected death. This study provides important insights into familial focal epilepsy and provides a preclinical model for evaluating potential therapies.

  4. Managing focal fields of vector beams with multiple polarization singularities.

    Science.gov (United States)

    Han, Lei; Liu, Sheng; Li, Peng; Zhang, Yi; Cheng, Huachao; Gan, Xuetao; Zhao, Jianlin

    2016-11-10

    We explore the tight focusing behavior of vector beams with multiple polarization singularities, and analyze the influences of the number, position, and topological charge of the singularities on the focal fields. It is found that the ellipticity of the local polarization states at the focal plane could be determined by the spatial distribution of the polarization singularities of the vector beam. When the spatial location and topological charge of singularities have even-fold rotation symmetry, the transverse fields at the focal plane are locally linearly polarized. Otherwise, the polarization state becomes a locally hybrid one. By appropriately arranging the distribution of the polarization singularities in the vector beam, the polarization distributions of the focal fields could be altered while the intensity maintains unchanged.

  5. Focal myositis of lower extremity responsive to botulinum A toxin.

    Science.gov (United States)

    Mitrovic, Josko; Prka, Zeljko; Zic, Rado; Marusic, Srecko; Morovic-Vergles, Jadranka

    2014-01-01

    Focal myositis is a rare, mostly benign disease (pseudotumor) of skeletal muscle, histopathologically characterized by interstitial myositis and tumorous enlargement of a single muscle. The etiology of focal myositis remains unknown; however, localized myopathy has been postulated to be caused by denervation lesions. This case report describes a patient that presented with clinical, laboratory, electromyoneurography, and magnetic resonance imaging features of focal myositis complicated with intervertebral disk protrusion in the lumbosacral spine affected with radicular distress. In most cases, focal myositic lesions show spontaneous regression, relapses are rare, and long-term prognosis is good. There is a wide spectrum of therapeutic options, from no therapy at all through nonsteroidal antirheumatics and glucocorticoids to radiotherapy, surgical excision, and immunosuppressants. In the patient presented, treatment with glucocorticoids, methotrexate, and surgical excision failed to produce satisfactory results. Clinical improvement, pain relief, and reduction in lower leg volume were only achieved by local infiltration of botulinum A toxin.

  6. Mechanical design and analysis of focal plate for gravity deformation

    Science.gov (United States)

    Wang, Jianping; Chu, Jiaru; Hu, Hongzhuan; Li, Kexuan; Zhou, Zengxiang

    2014-07-01

    The surface accuracy of astronomical telescope focal plate is a key indicator to precision stellar observation. To conduct accurate deformation measurement for focal plate in different status, a 6-DOF hexapod platform was used for attitude adjustment. For the small adjustment range of a classic 6-DOF hexapod platform, an improved structural arrangement method was proposed in the paper to achieve ultimate adjustment of the focal plate in horizontal and vertical direction. To validate the feasibility of this method, an angle change model which used ball hinge was set up for the movement and base plate. Simulation results in MATLAB suggested that the ball hinge angle change of movement and base plate is within the range of the limiting angle in the process of the platform plate adjusting to ultimate attitude. The proposed method has some guiding significance for accurate surface measurement of focal plate.

  7. FOCAL CORTICAL DYSPLASIAS: CLINICAL AND ELECTRO-NEUROIMAGING CHARACTERISTICS

    Directory of Open Access Journals (Sweden)

    K. Yu. Mukhin

    2016-01-01

    Full Text Available In spite of a notable advance made in epileptology, resistant epilepsies account for approximately 30 % of all forms of epilepsy particularly in patients with focal seizures. One of the main causes of therapy-resistant focal epilepsies is focal cortical dysplasias (FCD. This term was first introduced by D. Taylor et al. in 1971. FCD belongs to abnormal cortical development. Among all abnormalities of cortical development, FCD in surgically treated children amounts to 75 %. FCD is the most common cause of resistant epilepsy in children and the most frequent reason for diagnosing cryptogenic focal epilepsy with intractable seizures. The author gives a detailed literature review dedicated to FCD as a cause of resistant epilepsy, including the classification and histologic characteristics of FCD, its clinical manifestations and prognosis, and approaches to medical and surgical treatments. 

  8. Electrocorticographic discharge patterns in glioneuronal tumors and focal cortical dysplasia

    NARCIS (Netherlands)

    Ferrier, Cyrille H.; Aronica, Eleanora; Leijten, Frans S. S.; Spliet, Wim G. M.; van Huffelen, Alexander C.; van Rijen, Peter C.; Binnie, Colin D.

    2006-01-01

    PURPOSE: To determine whether highly epileptiform electrocorticographical discharge patterns occur in patients with glioneuronal tumors (GNTs) and focal cortical dysplasia (FCD) and whether specific histopathological features are related to such patterns. METHODS: The series consists of operated

  9. Adult-onset Rasmussen encephalitis associated with focal cortical dysplasia.

    Science.gov (United States)

    Hohenbichler, Katharina; Lelotte, Julie; Lhommel, Renaud; Tahry, Riëm El; Vrielynck, Pascal; Santos, Susana Ferrao

    2017-12-01

    Rasmussen encephalitis is a rare, devastating condition, typically presenting in childhood. Cases of adult-onset Rasmussen have also been described, but the clinical picture is less defined, rendering final diagnosis difficult. We present a case of adult-onset Rasmussen encephalitis with dual pathology, associated with focal cortical dysplasia and encephalitis. We interpreted the Rasmussen encephalitis to be caused by severe and continuous epileptic activity due to focal cortical dysplasia. The best therapeutic approach for such cases remains unclear.

  10. Focal plane for the next generation of earth observation instruments

    Science.gov (United States)

    Pranyies, P.; Toubhans, I.; Badoil, B.; Tanguy, F.; Descours, Francis

    2017-09-01

    Sodern is the French focal plane provider for Earth Observation (EO) satellites. Since the 1980's, Sodern has played an active role first in the SPOT program. Within the two-spacecraft constellation Pleiades 1A/1B over the next years, Sodern introduced advanced technologies as Silicon Carbide (SiC) focal plane structure and multispectral strip filters dedicated to multiple-lines detectors.

  11. THERMAL EFFECTS ON CAMERA FOCAL LENGTH IN MESSENGER STAR CALIBRATION AND ORBITAL IMAGING

    Directory of Open Access Journals (Sweden)

    S. Burmeister

    2018-04-01

    Full Text Available We analyse images taken by the MErcury Surface, Space ENviorment, GEochemistry, and Ranging (MESSENGER spacecraft for the camera’s thermal response in the harsh thermal environment near Mercury. Specifically, we study thermally induced variations in focal length of the Mercury Dual Imaging System (MDIS. Within the several hundreds of images of star fields, the Wide Angle Camera (WAC typically captures up to 250 stars in one frame of the panchromatic channel. We measure star positions and relate these to the known star coordinates taken from the Tycho-2 catalogue. We solve for camera pointing, the focal length parameter and two non-symmetrical distortion parameters for each image. Using data from the temperature sensors on the camera focal plane we model a linear focal length function in the form of f(T = A0 + A1 T. Next, we use images from MESSENGER’s orbital mapping mission. We deal with large image blocks, typically used for the production of a high-resolution digital terrain models (DTM. We analyzed images from the combined quadrangles H03 and H07, a selected region, covered by approx. 10,600 images, in which we identified about 83,900 tiepoints. Using bundle block adjustments, we solved for the unknown coordinates of the control points, the pointing of the camera – as well as the camera’s focal length. We then fit the above linear function with respect to the focal plane temperature. As a result, we find a complex response of the camera to thermal conditions of the spacecraft. To first order, we see a linear increase by approx. 0.0107 mm per degree temperature for the Narrow-Angle Camera (NAC. This is in agreement with the observed thermal response seen in images of the panchromatic channel of the WAC. Unfortunately, further comparisons of results from the two methods, both of which use different portions of the available image data, are limited. If leaving uncorrected, these effects may pose significant difficulties in

  12. Inverse-designed stretchable metalens with tunable focal distance

    Science.gov (United States)

    Callewaert, Francois; Velev, Vesselin; Jiang, Shizhou; Sahakian, Alan Varteres; Kumar, Prem; Aydin, Koray

    2018-02-01

    In this paper, we present an inverse-designed 3D-printed all-dielectric stretchable millimeter wave metalens with a tunable focal distance. A computational inverse-design method is used to design a flat metalens made of disconnected polymer building blocks with complex shapes, as opposed to conventional monolithic lenses. The proposed metalens provides better performance than a conventional Fresnel lens, using lesser amount of material and enabling larger focal distance tunability. The metalens is fabricated using a commercial 3D-printer and attached to a stretchable platform. Measurements and simulations show that the focal distance can be tuned by a factor of 4 with a stretching factor of only 75%, a nearly diffraction-limited focal spot, and with a 70% relative focusing efficiency, defined as the ratio between power focused in the focal spot and power going through the focal plane. The proposed platform can be extended for design and fabrication of multiple electromagnetic devices working from visible to microwave radiation depending on scaling of the devices.

  13. Thermomechanical architecture of the VIS focal plane for Euclid

    International Nuclear Information System (INIS)

    Martignac, Jerome; Carty, Michael; Tourette, Thierry; Bachet, Damien; Berthe, Michel; Augueres, Jean-Louis; Amiaux, Jerome; Fontignie, Jean; Horeau, Benoit; Renaud, Diana

    2014-01-01

    One of the main challenges for current and near future space experiments is the increase of focal plane complexity in terms of amount of pixels. In the frame work of the ESA Euclid mission to be launched in 2020, the Euclid Consortium is developing an extremely large and stable focal plane for the VIS instrument. CEA has developed the thermomechanical architecture of that Focal Plane taking into account all the very stringent performance and mission related requirements. The VIS Focal Plane Assembly integrates 36 CCDs (operated at 150 K) connected to their front end electronics (operated at 280 K) as to obtain one of the largest focal plane (0.6 billion pixels) ever built for space application after the GAIA one. The CCDs are CCD273 type specially designed and provided by the e2v company under ESA contract, front end electronics is studied and provided by MSSL. In this paper we first recall the specific requirements that have driven the overall architecture of the VIS-FPA and especially the solutions proposed to cope with the scientific needs of an extremely stable focal plane, both mechanically and thermally. The mechanical structure based on SiC material used for the cold sub assembly supporting the CCDs is detailed. We describe also the modular architecture concept that we have selected taking into account AIT-AIV and programmatic constraints. (authors)

  14. An ionization-chamber type of focal-plane detector for heavy ions

    International Nuclear Information System (INIS)

    Erskine, J.R.; Braid, T.H.; Stolfzfus, J.C.

    1976-01-01

    A focal-plane detector for heavy ions is described in which energy loss and total energy are measured with a gridded ionization chamber, and position along the focal plane and angle of incidence are measured with two resistive-wire proportional counters. The clean geometry of the detector makes it especially attractive for use with heavy ions of high specific ionization. Typical position resolutions of 1.0-1.5mm (fwhm) were observed over a 50 cm length of the detector in the focal plane of a split-pole magnetic spectrograph. Special tests were made which suggest that the limiting position resolution is 0.76 mm or better. The resolution of the energy-loss signal was typically 4.5% (fwhm). The resolution of the total energy signal was 1.0-1.5% (fwhm) for small entrance apertures of the spectrograph, although 0.7% resolution was observed under special circumstances. The angle of incidence was measured with an uncertainty of about 1.2% (fwhm). The availability of the many parameters needed for particle identification makes this detector especially useful for the study of weak reaction channels in heavy-ion-induced reactions. (Auth.)

  15. Blaschko Linear Enamel Defects - A Marker for Focal Dermal Hypoplasia: Case Report of Focal Dermal Hypoplasia

    Directory of Open Access Journals (Sweden)

    Stefan Gysin

    2015-05-01

    Full Text Available Focal dermal hypoplasia (FDH is a rare genetic skin disorder. The inheritance of FDH or Goltz-Gorlin syndrome is X-linked dominant and the disease is associated with a PORCN gene mutation. This gene plays a key role in the Wnt pathway, which has an impact on embryonic development. Every tissue derived from meso- and ectoderm can be affected. Patients suffer from cutaneous, ocular, osseous, oral and dental defects. The skin and dental alterations manifest along the Blaschko lines. We present a woman (born in 1962 suffering from FDH with congenital skin changes and Blaschko linear enamel defects. Typical symptoms (e.g. fat herniations, scoliosis, syndactyly, microphthalmia, caries and alopecia plus vertical grooving of all teeth gave a first indication. Molecular genetic testing confirmed the definitive diagnosis of FDH. We hypothesize that, in the context of typical skin changes, visible Blaschko lines on the teeth in the form of vertical grooves are almost pathognomonic for FDH.

  16. Perampanel for focal epilepsy: insights from early clinical experience.

    Science.gov (United States)

    Trinka, E; Steinhoff, B J; Nikanorova, M; Brodie, M J

    2016-03-01

    Perampanel is approved for adjunctive therapy of focal epilepsy with or without secondarily generalized seizures in patients aged >12 years. This narrative review uses real-world and clinical trial data to elucidate perampanel's role in the clinic. Audit data show good tolerability with perampanel and higher freedom-from-seizure rates in elderly vs younger patients. When using perampanel in elderly patients, special attention should be given to comorbidities and co-medication to avoid potential interactions or adverse events. Slower titration is generally recommended, and seizure control should be reassessed at a dose of 4 mg before further dose increases. Perampanel efficacy is similar in adolescents and adults; however, somnolence, nasopharyngitis, and aggression are more frequent in adolescents vs the overall population. Individualized and slow-dose titration can minimize adverse events. Low serum concentrations of perampanel may occur in patients also receiving some enzyme-inducing anti-epileptic drugs; a perampanel dose increase may be required. Adverse events of importance with perampanel include dizziness; anger, aggression, and hostile behavior (particularly in adolescents); and falls (particularly in patients >65 years). An individualized approach to dosing, including slower up-titration and bedtime dosing, reduces dizziness risk. Other drugs may cause or aggravate dizziness; reducing concomitant drugs may be necessary when up-titrating perampanel. It would seem clinically appropriate to give due consideration to avoiding use in patients with a history of anger or hostile/aggressive behavior. The possibility of such behaviors should be discussed with patients before starting perampanel, with monitoring during up-titration. Slower up-titration of perampanel in older patients helps reduce fall risk. © 2015 The Authors. Acta Neurologica Scandinavica Published by John Wiley & Sons Ltd.

  17. Joint Source Location and Focal Mechanism Inversion: efficiency, accuracy and applications

    Science.gov (United States)

    Liang, C.; Yu, Y.

    2017-12-01

    The analysis of induced seismicity has become a common practice to evaluate the results of hydraulic fracturing treatment. Liang et al (2016) proposed a joint Source Scanning Algorithms (jSSA for short) to obtain microseismic events and focal mechanisms simultaneously. The jSSA is superior over traditional SSA in many aspects, but the computation cost is too significant to be applied in real time monitoring. In this study, we have developed several scanning schemas to reduce computation time. A multi-stage scanning schema is proved to be able to improve the efficiency significantly while also retain its accuracy. A series of tests have been carried out by using both real field data and synthetic data to evaluate the accuracy of the method and its dependence on noise level, source depths, focal mechanisms and other factors. The surface-based arrays have better constraints on horizontal location errors (0.5). For sources with varying rakes, dips, strikes and depths, the errors are mostly controlled by the partition of positive and negative polarities in different quadrants. More evenly partitioned polarities in different quadrants yield better results in both locations and focal mechanisms. Nevertheless, even with bad resolutions for some FMs, the optimized jSSA method can still improve location accuracies significantly. Based on much more densely distributed events and focal mechanisms, a gridded stress inversion is conducted to get a evenly distributed stress field. The full potential of the jSSA has yet to be explored in different directions, especially in earthquake seismology as seismic array becoming incleasingly dense.

  18. Metallothionein-1+2 protect the CNS after a focal brain injury

    DEFF Research Database (Denmark)

    Giralt, Mercedes; Penkowa, Milena; Lago, Natalia

    2002-01-01

    We have evaluated the physiological relevance of metallothionein-1+2 (MT-1+2) in the CNS following damage caused by a focal cryolesion onto the cortex. In comparison to normal mice, transgenic mice overexpressing the MT-1 isoform (TgMTI* mice) showed a significant decrease of the number...... dramatically reduced the cryolesion-induced oxidative stress and neuronal apoptosis. Remarkably, these effects were also obtained by the intraperitoneal administration of MT-2 to both normal and MT-1+2 knock-out mice. These results fully support the notion that MT-1+2 are essential in the CNS for coping...

  19. Capillary Pressure-induced Lung Injury: Fact or Fiction?

    African Journals Online (AJOL)

    QuickSilver

    2003-05-07

    May 7, 2003 ... ing severe exercise, thus causing significant capillary hyper- tension. Pulmonary ... sponses evoked by high-pressure stress. To clarify the .... by an increased release of the vasoconstrictor endothelin-1 and thromboxane A2.

  20. Inflammation response at the transcriptional level of HepG2 cells induced by multi-walled carbon nanotubes

    International Nuclear Information System (INIS)

    Piret, Jean-Pascal; Vankoningsloo, Sebastien; Noel, Florence; Saout, Christelle; Toussaint, Olivier; Mendoza, Jorge Mejia; Lucas, Stephane

    2011-01-01

    Poor information are currently available about the biological effects of multi-walled carbon nanotubes (MWCNT) on the liver. In this study, we evaluated the effects of MWCNT at the transcriptional level on the classical in vitro model of HepG2 hepatocarcinoma cells. The expression levels of 96 transcript species implicated in the inflammatory and immune responses was studied after a 24h incubation of HepG2 cells in presence of raw MWCNT dispersed in water by stirring. Among the 46 transcript species detected, only a few transcripts including mRNA coding for interleukine-7, chemokines receptor of the C-C families CCR7, as well as Endothelin-1, were statistically more abundant after treatment with MWCNT. Altogether, these data indicate that MWCNT can only induce a weak inflammatory response in HepG2 cells.

  1. Inflammation response at the transcriptional level of HepG2 cells induced by multi-walled carbon nanotubes

    Science.gov (United States)

    Piret, Jean-Pascal; Vankoningsloo, Sébastien; Noël, Florence; Mejia Mendoza, Jorge; Lucas, Stéphane; Saout, Christelle; Toussaint, Olivier

    2011-07-01

    Poor information are currently available about the biological effects of multi-walled carbon nanotubes (MWCNT) on the liver. In this study, we evaluated the effects of MWCNT at the transcriptional level on the classical in vitro model of HepG2 hepatocarcinoma cells. The expression levels of 96 transcript species implicated in the inflammatory and immune responses was studied after a 24h incubation of HepG2 cells in presence of raw MWCNT dispersed in water by stirring. Among the 46 transcript species detected, only a few transcripts including mRNA coding for interleukine-7, chemokines receptor of the C-C families CCR7, as well as Endothelin-1, were statistically more abundant after treatment with MWCNT. Altogether, these data indicate that MWCNT can only induce a weak inflammatory response in HepG2 cells.

  2. CT findings of focal organizing pneumonia: correlation with pathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yang Soo; Kim, Young Goo; Park, Un Sup [College of Medicine, Chungang University, Seoul (Korea, Republic of)

    1994-11-15

    To evaluate the CT findings of focal organizing pneumonia and to correlate them with pathologic findings to help differentiating from lung cancer. We evaluated radiologic and pathologic findings of five patients with solitary pulmonary nodule which were confirmed as focal organizing pneumonia pathologically. On CT scan, focal organizing pneumonia had irregular margin contacting the pleura in all five cases. The shape of the nodules were spherical to wedge or elliptical and the size from 3.5cm to 5.5cm(average 4.2 cm) in largest diameter. On postcontrast CT scan, all nodules showed enhancement and four cases showed central low density components. Two nodules contained air within the nodule. In four cases, pleural changes such as effusion and/or focal thickening were noted. No lymphadenopathy was found in all cases. Pathologically, the enhancing portion on CT showed findings of organizing pneumonia such as granulation tissue with fibroblast proliferation in alveolar space and interstitial thickening. The central low density areas on CT were due to ischemic necrosis, abscess and exudate, transudate and infiltration of foamy histiocyte. The possibility of focal organizing pneumonia should be considered when peripherally located solitary pulmonary nodule had enhancing component with no combined lymphadenopathy on CT scan.

  3. CT findings of focal organizing pneumonia: correlation with pathologic findings

    International Nuclear Information System (INIS)

    Kim, Yang Soo; Kim, Young Goo; Park, Un Sup

    1994-01-01

    To evaluate the CT findings of focal organizing pneumonia and to correlate them with pathologic findings to help differentiating from lung cancer. We evaluated radiologic and pathologic findings of five patients with solitary pulmonary nodule which were confirmed as focal organizing pneumonia pathologically. On CT scan, focal organizing pneumonia had irregular margin contacting the pleura in all five cases. The shape of the nodules were spherical to wedge or elliptical and the size from 3.5cm to 5.5cm(average 4.2 cm) in largest diameter. On postcontrast CT scan, all nodules showed enhancement and four cases showed central low density components. Two nodules contained air within the nodule. In four cases, pleural changes such as effusion and/or focal thickening were noted. No lymphadenopathy was found in all cases. Pathologically, the enhancing portion on CT showed findings of organizing pneumonia such as granulation tissue with fibroblast proliferation in alveolar space and interstitial thickening. The central low density areas on CT were due to ischemic necrosis, abscess and exudate, transudate and infiltration of foamy histiocyte. The possibility of focal organizing pneumonia should be considered when peripherally located solitary pulmonary nodule had enhancing component with no combined lymphadenopathy on CT scan

  4. Detection is unaffected by the deployment of focal attention

    Directory of Open Access Journals (Sweden)

    Jeff eMoher

    2013-05-01

    Full Text Available There has been much debate regarding how much information humans can extract from their environment without the use of limited attentional resources. In a recent study, Theeuwes, Van der Burg, and Belopolsky (2008 argued that even detection of simple feature targets is not possible without selection by focal attention. Supporting this claim, they found response time benefits in a simple feature (color detection task when a target letter’s identity was repeated on consecutive trials, suggesting that the letter was selected by focal attention and identified prior to detection. This intertrial repetition benefit remained even when observers were required to simultaneously identify a central digit. However, we found that intertrial repetition benefits disappeared when a simple color target was presented among a heterogeneously (rather than homogeneously colored set of distractors, thus reducing its bottom-up salience. Still, detection performance remained high. Thus, detection performance was unaffected by whether a letter was focally attended and identified prior to detection or not. Intertrial identity repetition benefits also disappeared when observers were required to perform a simultaneous, attention-demanding central task (Experiment 2, or when unfamiliar Chinese characters were used (Experiment 3. Together, these results suggest that while shifts of focal attention can be affected by target salience, by the availability of excess cognitive resources, and by target familiarity, detection performance itself is unaffected by these manipulations and is thus unaffected by the deployment of focal attention.

  5. EEG dynamical correlates of focal and diffuse causes of coma.

    Science.gov (United States)

    Kafashan, MohammadMehdi; Ryu, Shoko; Hargis, Mitchell J; Laurido-Soto, Osvaldo; Roberts, Debra E; Thontakudi, Akshay; Eisenman, Lawrence; Kummer, Terrance T; Ching, ShiNung

    2017-11-15

    Rapidly determining the causes of a depressed level of consciousness (DLOC) including coma is a common clinical challenge. Quantitative analysis of the electroencephalogram (EEG) has the potential to improve DLOC assessment by providing readily deployable, temporally detailed characterization of brain activity in such patients. While used commonly for seizure detection, EEG-based assessment of DLOC etiology is less well-established. As a first step towards etiological diagnosis, we sought to distinguish focal and diffuse causes of DLOC through assessment of temporal dynamics within EEG signals. We retrospectively analyzed EEG recordings from 40 patients with DLOC with consensus focal or diffuse culprit pathology. For each recording, we performed a suite of time-series analyses, then used a statistical framework to identify which analyses (features) could be used to distinguish between focal and diffuse cases. Using cross-validation approaches, we identified several spectral and non-spectral EEG features that were significantly different between DLOC patients with focal vs. diffuse etiologies, enabling EEG-based classification with an accuracy of 76%. Our findings suggest that DLOC due to focal vs. diffuse injuries differ along several electrophysiological parameters. These results may form the basis of future classification strategies for DLOC and coma that are more etiologically-specific and therefore therapeutically-relevant.

  6. A targeted resequencing gene panel for focal epilepsy.

    Science.gov (United States)

    Hildebrand, Michael S; Myers, Candace T; Carvill, Gemma L; Regan, Brigid M; Damiano, John A; Mullen, Saul A; Newton, Mark R; Nair, Umesh; Gazina, Elena V; Milligan, Carol J; Reid, Christopher A; Petrou, Steven; Scheffer, Ingrid E; Berkovic, Samuel F; Mefford, Heather C

    2016-04-26

    We report development of a targeted resequencing gene panel for focal epilepsy, the most prevalent phenotypic group of the epilepsies. The targeted resequencing gene panel was designed using molecular inversion probe (MIP) capture technology and sequenced using massively parallel Illumina sequencing. We demonstrated proof of principle that mutations can be detected in 4 previously genotyped focal epilepsy cases. We searched for both germline and somatic mutations in 251 patients with unsolved sporadic or familial focal epilepsy and identified 11 novel or very rare missense variants in 5 different genes: CHRNA4, GRIN2B, KCNT1, PCDH19, and SCN1A. Of these, 2 were predicted to be pathogenic or likely pathogenic, explaining ∼0.8% of the cohort, and 8 were of uncertain significance based on available data. We have developed and validated a targeted resequencing panel for focal epilepsies, the most important clinical class of epilepsies, accounting for about 60% of all cases. Our application of MIP technology is an innovative approach that will be advantageous in the clinical setting because it is highly sensitive, efficient, and cost-effective for screening large patient cohorts. Our findings indicate that mutations in known genes likely explain only a small proportion of focal epilepsy cases. This is not surprising given the established clinical and genetic heterogeneity of these disorders and underscores the importance of further gene discovery studies in this complex syndrome. © 2016 American Academy of Neurology.

  7. Terapia Interpessoal: um modelo breve e focal Interpersonal Therapy: a brief and focal model

    Directory of Open Access Journals (Sweden)

    Marcelo Feijó de Mello

    2004-06-01

    Full Text Available A psicoterapia é uma forma particular de tratamento em psiquiatria. Seu uso é amplamente difundido e conta com várias linhas de abordagem. OBJETIVO: Neste trabalho, o autor faz considerações a respeito da terapia interpessoal (TIP, uma forma breve e focal de psicoterapia. Inicialmente usada para o tratamento da depressão, teve seu espectro de ação ampliado para outros transtornos. A TIP pode ser dividida em 3 fases: inicial, quando é feito um diagnóstico do transtorno nomeando os sintomas ao paciente e diagnosticando o foco interpessoal a ser trabalhado; fase intermediária, onde se trabalha o foco; e fase final, quando o paciente é encorajado a reconhecer e consolidar seus ganhos para usá-los no futuro. MÉTODOS: O autor faz uma revisão das evidências científicas da eficácia da TIP no tratamento da depressão. CONCLUSÕES: Os resultados mostram que a TIP é uma forma terapêutica eficaz e bem tolerada de tratamento para a depressão.Psychotherapy is a particular form of treatment in Psychiatry. Its use is widespread and has many different approaches. OBJECTIVE: In this article, the author makes some considerations about Interpersonal Therapy (IPT, a brief and focal psychotherapy. Initially created to treat depression, other researchers had successfully increase its spectrum. It could be divided in three phases. Initial, when the therapist makes the diagnosis of the disorder and also the interpersonal problematic is pointed out; the patient received a sick role. Intermediary when the focus is treated, and the final phase when the therapist encourages the patient to recognize and consolidate gains and prepare the patient to use it in the future. METHODS: It is stressed that IPT is a testable form of psychotherapy and the scientific evidences of its efficacy are showed. CONCLUSIONS: The results assure that IPT is an efficient form of psychotherapy for depression with a great acceptability from the patients.

  8. Role of scintigraphy in focally abnormal sonograms of fatty livers

    International Nuclear Information System (INIS)

    Lisbona, R.; Mishkin, S.; Derbekyan, V.; Novales-Diaz, J.A.; Roy, A.; Sanders, L.

    1988-01-01

    Fatty infiltration of the liver may cause a range of focal abnormalities on hepatic sonography which may simulate hepatic nodular lesions. Discrete deposits of fat or islands of normal tissue which are uninvolved by fatty infiltration may stand out as potential space-occupying lesions on the sonograms. Twelve patients with such focally abnormal ultrasound images were referred for liver scintigraphy with 133 Xe and /sup 99m/Tc colloidal SPECT studies to clarify the issue. These examinations helped identify, in nine of 12 patients, the innocent nature of the sonographic abnormalities which were simply related to the fat deposition process. Further, [/sup 99m/Tc]RBC scans defined the additional pathologic process in three patients in whom actual space-occupying lesions were indeed present in the liver. Scintigraphy has an important role to play in the understanding of focal hepatic ultrasound abnormalities particularly in unsuspected hepatic steatosis

  9. Role of scintigraphy in focally abnormal sonograms of fatty livers

    Energy Technology Data Exchange (ETDEWEB)

    Lisbona, R.; Mishkin, S.; Derbekyan, V.; Novales-Diaz, J.A.; Roy, A.; Sanders, L.

    1988-06-01

    Fatty infiltration of the liver may cause a range of focal abnormalities on hepatic sonography which may simulate hepatic nodular lesions. Discrete deposits of fat or islands of normal tissue which are uninvolved by fatty infiltration may stand out as potential space-occupying lesions on the sonograms. Twelve patients with such focally abnormal ultrasound images were referred for liver scintigraphy with /sup 133/Xe and /sup 99m/Tc colloidal SPECT studies to clarify the issue. These examinations helped identify, in nine of 12 patients, the innocent nature of the sonographic abnormalities which were simply related to the fat deposition process. Further, (/sup 99m/Tc)RBC scans defined the additional pathologic process in three patients in whom actual space-occupying lesions were indeed present in the liver. Scintigraphy has an important role to play in the understanding of focal hepatic ultrasound abnormalities particularly in unsuspected hepatic steatosis.

  10. US and CT findings in splenic focal lesions in AIDS

    International Nuclear Information System (INIS)

    Schinina, V.; Rizzi, E.B.; Mazzuoli, G.; Bibbolilno, C.; David, V.

    2000-01-01

    To evaluate the role of US and CT in focal splenic lesions in AIDS patients in relation to etiology. Material and Methods: A total of 66 patients with AIDS and focal splenic lesions were examined with sonography. CT with administration of contrast medium was performed in 12 cases. Results: Of the focal splenic lesions, 67% were correlated with an infective pathology with prevalence of Mycobacteria tuberculosis (75%), 26% were neoplastic and 6% splenic infarcts. The lesions were hypoechoic in 60% of the cases, while 10% were hypoanechoic and 1% anechoic. At CT, all lesions appeared hypodense, even after i.v. administration of contrast medium. Conclusion: The combination of echographic reports and clinical and laboratory data allows for a diagnosis that can be confirmed, and making a decision for effective therapy of AIDS is possible. CT does not provide any additional information

  11. Simulation of the Focal Spot of the Accelerator Bremsstrahlung Radiation

    Science.gov (United States)

    Sorokin, V.; Bespalov, V.

    2016-06-01

    Testing of thick-walled objects by bremsstrahlung radiation (BR) is primarily performed via high-energy quanta. The testing parameters are specified by the focal spot size of the high-energy bremsstrahlung radiation. In determining the focal spot size, the high- energy BR portion cannot be experimentally separated from the low-energy BR to use high- energy quanta only. The patterns of BR focal spot formation have been investigated via statistical modeling of the radiation transfer in the target material. The distributions of BR quanta emitted by the target for different energies and emission angles under normal distribution of the accelerated electrons bombarding the target have been obtained, and the ratio of the distribution parameters has been determined.

  12. MRI of a family with focal abnormalities of gyration

    International Nuclear Information System (INIS)

    Muntaner, L.; Perez-Ferron, J.J.; Herrera, M.; Rosell, J.; Taboada, D.; Climent, S.

    1997-01-01

    Focal abnormalities of gyration (FAG) are developmental disorders that may occur in isolated patients or, as in the case being reported, as part of a familial disorder. Analysis of individuals in a family spanning three generations was carried out using MRI. Abnormalities, present in all members of generations II and III, included focal cortical dysplasia (three patients), focal cortical infolding (two patients) and schizencephaly (one patient); associated minor anomalies, such as white matter abnormalities, were seen in the remaining three members of generations II and III. MRI recognition of FAG in the family being reported proved useful in defining their phenotypical expression and providing proper counselling for individual family members. (orig.). With 6 figs

  13. Protein kinase C involvement in focal adhesion formation

    DEFF Research Database (Denmark)

    Woods, A; Couchman, J R

    1992-01-01

    Matrix molecules such as fibronectin can promote cell attachment, spreading and focal adhesion formation. Although some interactions of fibronectin with cell surface receptors have now been identified, the consequent activation of intracellular messenger systems by cell/matrix interactions have...... still to be elucidated. We show here that the kinase inhibitors H7 and HA1004 reduce focal adhesion and stress fiber formation in response to fibronectin in a dose-dependent manner, and that activators of protein kinase C can promote their formation under conditions where they do not normally form....... Fibroblasts spread within 1h on substrata composed of fibronectin and formed focal adhesions by 3h, as monitored by interference reflection microscopy (IRM) and by labeling for talin, vinculin and integrin beta 1 subunits. In addition, stress fibers were visible. When cells were allowed to spread for 1h...

  14. Focal depth measurement of scanning helium ion microscope

    International Nuclear Information System (INIS)

    Guo, Hongxuan; Itoh, Hiroshi; Wang, Chunmei; Zhang, Han; Fujita, Daisuke

    2014-01-01

    When facing the challenges of critical dimension measurement of complicated nanostructures, such as of the three dimension integrated circuit, characterization of the focal depth of microscopes is important. In this Letter, we developed a method for characterizing the focal depth of a scanning helium ion microscope (HIM) by using an atomic force microscope tip characterizer (ATC). The ATC was tilted in a sample chamber at an angle to the scanning plan. Secondary electron images (SEIs) were obtained at different positions of the ATC. The edge resolution of the SEIs shows the nominal diameters of the helium ion beam at different focal levels. With this method, the nominal shapes of the helium ion beams were obtained with different apertures. Our results show that a small aperture is necessary to get a high spatial resolution and high depth of field images with HIM. This work provides a method for characterizing and improving the performance of HIM.

  15. Earthquake focal mechanism forecasting in Italy for PSHA purposes

    Science.gov (United States)

    Roselli, Pamela; Marzocchi, Warner; Mariucci, Maria Teresa; Montone, Paola

    2018-01-01

    In this paper, we put forward a procedure that aims to forecast focal mechanism of future earthquakes. One of the primary uses of such forecasts is in probabilistic seismic hazard analysis (PSHA); in fact, aiming at reducing the epistemic uncertainty, most of the newer ground motion prediction equations consider, besides the seismicity rates, the forecast of the focal mechanism of the next large earthquakes as input data. The data set used to this purpose is relative to focal mechanisms taken from the latest stress map release for Italy containing 392 well-constrained solutions of events, from 1908 to 2015, with Mw ≥ 4 and depths from 0 down to 40 km. The data set considers polarity focal mechanism solutions until to 1975 (23 events), whereas for 1976-2015, it takes into account only the Centroid Moment Tensor (CMT)-like earthquake focal solutions for data homogeneity. The forecasting model is rooted in the Total Weighted Moment Tensor concept that weighs information of past focal mechanisms evenly distributed in space, according to their distance from the spatial cells and magnitude. Specifically, for each cell of a regular 0.1° × 0.1° spatial grid, the model estimates the probability to observe a normal, reverse, or strike-slip fault plane solution for the next large earthquakes, the expected moment tensor and the related maximum horizontal stress orientation. These results will be available for the new PSHA model for Italy under development. Finally, to evaluate the reliability of the forecasts, we test them with an independent data set that consists of some of the strongest earthquakes with Mw ≥ 3.9 occurred during 2016 in different Italian tectonic provinces.

  16. Nodular focal fatty infiltration of the liver: CT appearance

    International Nuclear Information System (INIS)

    Baker, M.E.; Silverman, P.M.

    1985-01-01

    Focal fatty infiltration of the liver is a well recognized entity generally characterized by a nonspherical, low-density area without significant mass effect. CT usually distinguishes this from focal liver processes such as abscess or metastasis by its sharply marginated, geographic pattern and lack of mass effect on hepatic and portal veins. Recently, the authors formed a CT scan of the liver in one patient in whom fatty infiltration appeared nodular or rounded. The clinical presentation and radiographic and pathologic features form the basis of this report

  17. The radiological features of Goltz syndrome: Focal dermal hypoplasia

    International Nuclear Information System (INIS)

    Boothyrod, A.E.; Hall, C.M.

    1988-01-01

    Two female infants with Goltz syndrome (focal dermal hypoplasia) were recently investigated for severe feeding problems and failure to thrive. Both demonstrated severe skeletal malformations and marked gastrooesophageal reflux with laxity of the hiatus. One child (case 1) exhibited nasal regurgitation during feeding. Interestingly, both children had undergone surgery; Case 1 or a right parasagittal abdominal hernia associated with focal dermal hypoplasia of the abdominal wall and Case 2 for an exomphalos also associated with dermal hypoplasia. This observation suggests more widespread mesodermal abnormality. (orig./GDG)

  18. Focal myositis of the thigh: unusual MR pattern

    International Nuclear Information System (INIS)

    Llauger, Jaume; Palmer, Jaume; San Roman, Luis; Bague, Silvia; Matias-Guiu, Xavier; Doncel, Antonio

    2002-01-01

    Focal myositis is a commonly referenced, infrequently reported and poorly documented benign inflammatory pseudotumor which may be misdiagnosed clinically as a malignant tumor. We report the clinicopathologic features and magnetic resonance imaging findings in a case of focal myositis in the thigh of a 55-year-old woman. A different radiologic presentation of this disorder is described. The gross appearance of the lesion, previously undescribed, appears to be rather specific for such a pseudoneoplastic disorder, and correlates very well with the magnetic resonance imaging features. (orig.)

  19. Focal myositis of the thigh: unusual MR pattern

    Energy Technology Data Exchange (ETDEWEB)

    Llauger, Jaume; Palmer, Jaume; San Roman, Luis [Department of Radiology, Hospital de la Santa Creu i Sant Pau, Barcelona (Spain); Bague, Silvia; Matias-Guiu, Xavier [Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona (Spain); Doncel, Antonio [Department of Orthopedic Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona (Spain)

    2002-05-01

    Focal myositis is a commonly referenced, infrequently reported and poorly documented benign inflammatory pseudotumor which may be misdiagnosed clinically as a malignant tumor. We report the clinicopathologic features and magnetic resonance imaging findings in a case of focal myositis in the thigh of a 55-year-old woman. A different radiologic presentation of this disorder is described. The gross appearance of the lesion, previously undescribed, appears to be rather specific for such a pseudoneoplastic disorder, and correlates very well with the magnetic resonance imaging features. (orig.)

  20. Magnetic-resonance-guided biopsy of focal liver lesions

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Ethan A. [University of Michigan Health System, Section of Pediatric Radiology, C.S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); Grove, Jason J. [University of Michigan Health System, Division of Interventional Radiology, C.S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); Der Spek, Abraham F.L.V. [University of Michigan Health System, Department of Anesthesiology, C.S. Mott Children' s Hospital, Ann Arbor, MI (United States); Jarboe, Marcus D. [University of Michigan Health System, Division of Interventional Radiology, C.S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); University of Michigan Health System, Section of Pediatric Surgery, C.S. Mott Children' s Hospital, Department of Surgery, Ann Arbor, MI (United States)

    2017-05-15

    Image-guided biopsy techniques are widely used in clinical practice. Commonly used methods employ either ultrasound (US) or computed tomography (CT) for image guidance. In certain patients, US or CT guidance may be suboptimal, or even impossible, because of artifacts, suboptimal lesion visualization, or both. We recently began performing magnetic resonance (MR)-guided biopsy of focal liver lesions in select pediatric patients with lesions that are not well visualized by US or CT. This report describes our experience performing MR-guided biopsy of focal liver lesions, with case examples to illustrate innovative techniques and novel aspects of these procedures. (orig.)

  1. Magnetic electroanatomical mapping for ablation of focal atrial tachycardias.

    Science.gov (United States)

    Marchlinski, F; Callans, D; Gottlieb, C; Rodriguez, E; Coyne, R; Kleinman, D

    1998-08-01

    Uniform success for ablation of focal atrial tachycardias has been difficult to achieve using standard catheter mapping and ablation techniques. In addition, our understanding of the complex relationship between atrial anatomy, electrophysiology, and surface ECG P wave morphology remains primitive. The magnetic electroanatomical mapping and display system (CARTO) offers an on-line display of electrical activation and/or signal amplitude related to the anatomical location of the recorded sites in the mapped chamber. A window of electrical interest is established based on signals timed from an electrical reference that usually represents a fixed electrogram recording from the coronary sinus or the atrial appendage. This window of electrical interest is established to include atrial activation prior to the onset of the P wave activity associated with the site of origin of a focal atrial tachycardia. Anatomical and electrical landmarks are defined with limited fluoroscopic imaging support and more detailed global chamber and more focal atrial mapping can be performed with minimal fluoroscopic guidance. A three-dimensional color map representing atrial activation or voltage amplitude at the magnetically defined anatomical sites is displayed with on-line data acquisition. This display can be manipulated to facilitate viewing from any angle. Altering the zoom control, triangle fill threshold, clipping plane, or color range can all enhance the display of a more focal area of interest. We documented the feasibility of using this single mapping catheter technique for localizing and ablating focal atrial tachycardias. In a consecutive series of 8 patients with 9 focal atrial tachycardias, the use of the single catheter CARTO mapping system was associated with ablation success in all but one patient who had a left atrial tachycardia localized to the medial aspect of the orifice of the left atrial appendage. Only low power energy delivery was used in this patient because of the

  2. Regional cerebral blood flow in focal cortical epilepsy

    DEFF Research Database (Denmark)

    Hougaard, Kristina Dupont; Oikawa, T; Sveinsdottir, E

    1976-01-01

    Regional cerebral blood flow (rCBF) was studied in ten patients with focal cortical epilepsy. The blood flow was measured by the intra-arterial injection of xenon 133 (133Xe), and the isotope clearance was recorded by a multidetector scintillation camera with 254 detectors. Three patients were....... This finding accords with earlier studies. All nine patients studied in the interictal phase showed, either spontaneously or during activation by intermittent light, focal flow increases in areas presumed to comprise the epileptic focus. These interictal hyperemic foci probably reflect subictal neuronal...

  3. Incidental Detection of Temporary Focal FDG Retention in the Spleen

    Energy Technology Data Exchange (ETDEWEB)

    Park, Youn Joon; Lee, Jai Hyuen; Jee, Keum Nahn; Namgung, Hwan [Dankook Univ. College of Medicine, Seoul (Korea, Republic of)

    2011-06-15

    F 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is a valuable tool in discriminating malignancy from benign lesion. But because various false positive results reduce the diagnostic specificity, nuclear medicine physicians should be familiar with possible false positive cases. Although many cases of high FDG uptake mimicking malignancy have been reported, temporary intense focal FDG uptake of normal spleen has not been reported previously. We report herein a phenomenon of temporary intense focal FDG uptake of normal spleen without evidence of metastasis in a 46 year old woman with a history of anal cancer.

  4. Expansion characteristics of coronary stents in focal stenoses

    Directory of Open Access Journals (Sweden)

    Schmidt Wolfram

    2017-09-01

    Full Text Available The presented experimental in vitro approach was designed to assess the expansion behavior of stent systems in a resistant focal stenosis model with respect to a potential dog-boning effect. Five different stent systems (nominal diameter 3.0 mm were investigated. The focal stenosis was simulated by a stainless steel tube (ID ≤ 1.20 mm. Stent expansion was performed using a proprietary test device consisting of a test chamber with 37 °C water, 2-axis laser scanner and a pressure controller.

  5. A Discovery Strategy for Selective Inhibitors of c-Src in Complex with the Focal Adhesion Kinase SH3/SH2-binding Region.

    Science.gov (United States)

    Moroco, Jamie A; Baumgartner, Matthew P; Rust, Heather L; Choi, Hwan Geun; Hur, Wooyoung; Gray, Nathanael S; Camacho, Carlos J; Smithgall, Thomas E

    2015-08-01

    The c-Src tyrosine kinase co-operates with the focal adhesion kinase to regulate cell adhesion and motility. Focal adhesion kinase engages the regulatory SH3 and SH2 domains of c-Src, resulting in localized kinase activation that contributes to tumor cell metastasis. Using assay conditions where c-Src kinase activity required binding to a tyrosine phosphopeptide based on the focal adhesion kinase SH3-SH2 docking sequence, we screened a kinase-biased library for selective inhibitors of the Src/focal adhesion kinase peptide complex versus c-Src alone. This approach identified an aminopyrimidinyl carbamate compound, WH-4-124-2, with nanomolar inhibitory potency and fivefold selectivity for c-Src when bound to the phospho-focal adhesion kinase peptide. Molecular docking studies indicate that WH-4-124-2 may preferentially inhibit the 'DFG-out' conformation of the kinase active site. These findings suggest that interaction of c-Src with focal adhesion kinase induces a unique kinase domain conformation amenable to selective inhibition. © 2014 John Wiley & Sons A/S.

  6. Quadruple Cone Coil with improved focality than Figure-8 coil in Transcranial Magnetic Stimulation

    Science.gov (United States)

    Rastogi, Priyam; Lee, Erik G.; Hadimani, Ravi L.; Jiles, David C.

    Transcranial Magnetic Stimulation (TMS) is a non-invasive therapy which uses a time varying magnetic field to induce an electric field in the brain and to cause neuron depolarization. Magnetic coils play an important role in the TMS therapy since their coil geometry determines the focality and penetration's depth of the induced electric field in the brain. Quadruple Cone Coil (QCC) is a novel coil with an improved focality when compared to commercial Figure-8 coil. The results of this newly designed QCC coil are compared with the Figure-8 coil at two different positions of the head - vertex and dorsolateral prefrontal cortex, over the 50 anatomically realistic MRI derived head models. Parameters such as volume of stimulation, maximum electric, area of stimulation and location of maximum electric field are determined with the help of computer modelling of both coils. There is a decrease in volume of brain stimulated by 11.6 % and a modest improvement of 8 % in the location of maximum electric field due to QCC in comparison to the Figure-8 coil. The Carver Charitable Trust and The Galloway Foundation.

  7. Histopathology of motor cortex in an experimental focal ischemic stroke in mouse model.

    Science.gov (United States)

    de Oliveira, Juçara Loli; Crispin, Pedro di Tárique Barreto; Duarte, Elisa Cristiana Winkelmann; Marloch, Gilberto Domingos; Gargioni, Rogério; Trentin, Andréa Gonçalves; Alvarez-Silva, Marcio

    2014-05-01

    Experimental ischemia results in cortical brain lesion followed by ischemic stroke. In this study, focal cerebral ischemia was induced in mice by occlusion of the middle cerebral artery. We studied cortical layers I, II/III, V and VI in the caudal forelimb area (CFA) and medial agranular cortex (AGm) from control and C57BL/6 mice induced with ischemic stroke. Based on our analysis of CFA and AGm motor cortex, significant differences were observed in the numbers of neurons, astrocytes and microglia in the superficial II/III and deep V cortical layers. Cellular changes were more prominent in layer V of the CFA with nuclear pyknosis, chromatin fragmentation, necrosis and degeneration, as well as, morphological evidence of apoptosis, mainly in neurons. As result, the CFA was more severely impaired than the AGm in this focal cerebral ischemic model, as evidenced by the proliferation of astrocytes, potentially resulting in neuroinflammation by microglia-like cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. The inhibitory effect of an extract of Sanguisorba officinalis L. on ultraviolet B-induced pigmentation via the suppression of endothelin-converting enzyme-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Hachiya, Akira; Kobayashi, Akemi; Ohuchi, Atsushi; Kitahara, Takashi; Takema, Yoshinori [Kao Biological Science Lab., Ichikai, Tochigi (Japan)

    2001-06-01

    Endothelin-1 (ET-1) has been reported to be expressed in human epidermis at both the gene and protein levels. ET-1 plays a pivotal role in ultraviolet B (UVB)-induced pigmentation due to its accentuated secretion after UVB irradiation and its function as a mitogen and as a melanogen for human melanocytes. We have recently found that endothelin-converting enzyme (ECE)-1{alpha} plays a constitutive role in the secretion of ET-1 by human keratinocytes and that an extract of Sanguisorba officinalis L. inhibits ECE activity in human endothelial cells, which predominantly express ECE-1{alpha}. In this report, to clarify the potential use of this botanical extract as a whitening agent, we examined whether this extract inhibits UVB-induced pigmentation in vivo. When this extract was applied to human keratinocytes after UVB irradiation, secretion of ET-1 by those cells was reduced, and this was accompanied by a concomitant increase in the secretion of inactive precursor Big endothelin-1. When hairless mice were exposed to UVB light and were treated with the extract, it suppressed the induction of ET-1 in the UVB-irradiated epidermis. In the course of UVB-induced pigmentation of brownish guinea pig skin, this extract significantly diminished pigmentation in UVB-exposed areas. These findings indicate that ECE-1{alpha} in keratinocytes plays a pivotal role in the induction of pigmentation following UVB irradiation and that an extract of S. officinalis, which inhibits ET-1 production in human keratinocytes, is a good ingredient for a whitening agent. (author)

  9. The inhibitory effect of an extract of Sanguisorba officinalis L. on ultraviolet B-induced pigmentation via the suppression of endothelin-converting enzyme-1α

    International Nuclear Information System (INIS)

    Hachiya, Akira; Kobayashi, Akemi; Ohuchi, Atsushi; Kitahara, Takashi; Takema, Yoshinori

    2001-01-01

    Endothelin-1 (ET-1) has been reported to be expressed in human epidermis at both the gene and protein levels. ET-1 plays a pivotal role in ultraviolet B (UVB)-induced pigmentation due to its accentuated secretion after UVB irradiation and its function as a mitogen and as a melanogen for human melanocytes. We have recently found that endothelin-converting enzyme (ECE)-1α plays a constitutive role in the secretion of ET-1 by human keratinocytes and that an extract of Sanguisorba officinalis L. inhibits ECE activity in human endothelial cells, which predominantly express ECE-1α. In this report, to clarify the potential use of this botanical extract as a whitening agent, we examined whether this extract inhibits UVB-induced pigmentation in vivo. When this extract was applied to human keratinocytes after UVB irradiation, secretion of ET-1 by those cells was reduced, and this was accompanied by a concomitant increase in the secretion of inactive precursor Big endothelin-1. When hairless mice were exposed to UVB light and were treated with the extract, it suppressed the induction of ET-1 in the UVB-irradiated epidermis. In the course of UVB-induced pigmentation of brownish guinea pig skin, this extract significantly diminished pigmentation in UVB-exposed areas. These findings indicate that ECE-1α in keratinocytes plays a pivotal role in the induction of pigmentation following UVB irradiation and that an extract of S. officinalis, which inhibits ET-1 production in human keratinocytes, is a good ingredient for a whitening agent. (author)

  10. Focal symmetrical encephalomalacia in sheep Encefalomalacia focal simétrica em ovino

    Directory of Open Access Journals (Sweden)

    Luciano A. Pimentel

    2010-05-01

    Full Text Available Focal symmetrical encephalomalacia (FSE is the most prominent lesion seen in the chronic form of enterotoxemia by Clostridium perfringens type D. This paper reports FSE in sheep in Brazil. Six deaths occurred within a seven days period in a flock of 70, four to 30-month-old Santa Inês sheep in the state of Paraíba in the Brazilian semiarid. The flock was grazing a paddock of irrigated sprouting Cynodon dactylon (Tifton grass, and supplemented, ad libitum, with a concentrate of soybean, corn and wheat. Nervous signs included blindness and recumbence. A 19 month-old sheep was examined clinically and necropsied after a clinical course of three days. Gross lesions were herniation of the cerebellar vermis and multifocal, bilateral, symmetric brownish areas in the internal capsule, thalamus and cerebellar peduncles. Histologic lesions were multifocal, bilateral malacia with some neutrophils, swelling of blood vessels endothelium, perivascular edema, and hemorrhages. The flock was vaccinated, before the outbreak, with only one dose of Clostridium perfringens type D vaccine. Two factors are suggested to be important for the occurrence of the disease: insufficient immunity due to the incorrect vaccination; and high nutritional levels by the supplementation with highly fermentable carbohydrates.Encefalomalacia focal simétrica (EFS é a lesão mais proeminente vista nas formas subaguda ou crônica da enterotoxemia por Clostridium perfringens tipo D. Este trabalho relata EFS em ovinos no semiárido do estado da Paraíba. Seis ovinos morreram, em um período de sete dias, dentro de um rebanho de 70 animais, da raça Santa Inês, entre 4-30 meses de idade, que pastavam em piquete de Cynodon dactylon (capim Tifton, que estava rebrotando. Os ovinos eram suplementados com um concentrado de soja, trigo e milho. Os sinais nervosos incluíam cegueira e decúbito lateral. Um ovino de 19 meses de idade foi examinado clinicamente e necropsiado, depois de um curso

  11. Pharmacokinetic Study of Piracetam in Focal Cerebral Ischemic Rats.

    Science.gov (United States)

    Paliwal, Pankaj; Dash, Debabrata; Krishnamurthy, Sairam

    2018-04-01

    Cerebral ischemia affects hepatic enzymes and brain permeability extensively. Piracetam was investigated up to phase III of clinical trials and there is lack of data on brain penetration in cerebral ischemic condition. Thus, knowledge of the pharmacokinetics and brain penetration of piracetam during ischemic condition would aid to improve pharmacotherapeutics in ischemic stroke. Focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h in male Wistar rats followed by reperfusion. After 24 h of middle cerebral artery occlusion or 22 h of reperfusion, piracetam was administered for pharmacokinetic, brain penetration, and pharmacological experiments. In pharmacokinetic study, blood samples were collected at different time points after 200-mg/kg (oral) and 75-mg/kg (intravenous) administration of piracetam through right external jugular vein cannulation. In brain penetration study, the cerebrospinal fluid, systemic blood, portal blood, and brain samples were collected at pre-designated time points after 200-mg/kg oral administration of piracetam. In a separate experiment, the pharmacological effect of the single oral dose of piracetam in middle cerebral artery occlusion was assessed at a dose of 200 mg/kg. All the pharmacokinetic parameters of piracetam including area under curve (AUC 0-24 ), maximum plasma concentration (C max ), time to reach the maximum plasma concentration (t max ), elimination half-life (t 1/2 ), volume of distribution (V z ), total body clearance, mean residence time, and bioavailability were found to be similar in ischemic stroke condition except for brain penetration. Piracetam exposure (AUC 0-2 ) in brain and CSF were found to be 2.4- and 3.1-fold higher, respectively, in ischemic stroke compared to control rats. Piracetam significantly reduced infarct volume by 35.77% caused by middle cerebral artery occlusion. There was no change in the pharmacokinetic parameters of piracetam in the ischemic stroke model except for

  12. Idiopathic focal segmental glomerulosclerosis: a favourable prognosis in untreated patients?

    NARCIS (Netherlands)

    Deegens, J.K.J.; Assmann, K.J.M.; Steenbergen, E.; Hilbrands, L.B.; Gerlag, P.G.G.; Jansen, J.L.; Wetzels, J.F.M.

    2005-01-01

    BACKGROUND: Patients with focal segmental glomerulosclerosis (FSGS) are considered to have a poor prognosis and spontaneous remissions are seldom reported. However, FSGS is not a single disease entity. Our aim was to describe the clinical course in initially untreated patients with recently

  13. Laser Beam Caustic Measurement with Focal Spot Analyser

    DEFF Research Database (Denmark)

    Olsen, Flemming Ove; Gong, Hui; Bagger, Claus

    2005-01-01

    In industrial applications of high power CO2-lasers the caustic characteristics of the laser beam have great effects on the performance of the lasers. A welldefined high intense focused spot is essential for reliable production results. This paper presents a focal spot analyser that is developed...

  14. Mass Equivalent Pantographs for Synthesis of Balanced Focal Mechanisms

    NARCIS (Netherlands)

    van der Wijk, V.; Lenarcic, Jadran; Merlet, Jean-Pierre

    2016-01-01

    Force balance is an important property in the design of high-speed high precision machinery to reduce base vibrations and also for the design of inherently safe large movable structures. This paper presents the synthesis of inherently balanced overconstrained focal mechanisms with mass equivalent

  15. A 1.3 giga pixels focal plane for GAIA

    Science.gov (United States)

    Laborie, Anouk; Pouny, Pierre; Vetel, Cyril; Collados, Emmanuel; Rougier, Gilles; Davancens, Robert; Zayer, Igor; Perryman, Michael; Pace, Oscar

    2004-06-01

    The astrometric mission GAIA is a cornerstone mission of the European Space Agency, due for launch in the 2010 time frame. Requiring extremely demanding performance GAIA calls for the development of an unprecedented large focal plane featuring innovative technologies. For securing the very challenging GAIA development, a significant number of technology activities have been initiated by ESA through a competitive selection process. In this context, an industrial consortium led by EADS-Astrium (France) with e2v technologies (UK) as major subcontractor was selected for the GAIA CCD and Focal Plane Technology Demonstrators programme, which is by far the most significant and the most critical GAIA pre-development for all aspects: science performance, development schedule and cost. This programme has started since August 2002 and will end early 2005 prior to commencement of the GAIA Phase B. While the GAIA payload will host three instruments and related focal planes, the major mission objectives are assigned to the Astrometric (ASTRO) Focal Plane, which is the subject of this presentation.

  16. Shared Focal Plane Investigation for Serial Frame Cameras.

    Science.gov (United States)

    1980-03-01

    capability will be restored. 41. -.. TrABLE 1-1 SYSTEM LEADING P) ARTICULARS Lens Focal Length (inches) Range (ft) Contrast 12 18 24 Coverage 22.1...can be expected that signature bands will be apparent in the imagery. Such bands are at best distracting and at worst hindrances to image interpretation

  17. Tratamento focal e perifocal contra Aëdes aegypti

    Directory of Open Access Journals (Sweden)

    Milton Moura Lima

    1987-06-01

    Full Text Available Em quatro bairros da cidade do Rio de Janeiro, foram feitos ensaios de tratamento focal com abate granulado a 1 ppm e perifocal com pó molhável de Sumition a 2,5%. Esses tratamentos foram feitos tanto isoladamente quanto em conjunto e, também, associados à aplicação de inseticida a ultrabaixo volume. Os índices prediais, levantados um mês depois de terminado o trabalho, mostraram que o tratamento focal dispensa qualquer medida auxiliar. O tratamento perifocal mostrou-se inócuo e incapaz de impedir o aparecimento de larvas de Aëdes aegypti e de outros insetos, em pneus pintados, na face externa, com Sumition e com Malation.In four districts of the city of Rio dc Janeiro focal treatment essays with granulated Abate at 1 ppm and perifocal treatment essays with wettable powder of Sumithion at 2,5% were performed. These were made either alone or in combination as well as associated to insecticides applied at ultra low volume. The premise indices obtained one month after the treatments indicates that the focal treatment alone is effective, no other addicional methods being necessary. The perifocal treatment is not effective and did not prevent the development of Aedes aegypti larvae and other insects in tires which had their external surface painted with Sumithion and Malathion.

  18. Axial and focal-plane diffraction catastrophe integrals

    International Nuclear Information System (INIS)

    Berry, M V; Howls, C J

    2010-01-01

    Exact expressions in terms of Bessel functions are found for some of the diffraction catastrophe integrals that decorate caustics in optics and mechanics. These are the axial and focal-plane sections of the elliptic and hyperbolic umbilic diffraction catastrophes, and symmetric elliptic and hyperbolic unfoldings of the X 9 diffraction catastrophes. These representations reveal unexpected relations between the integrals.

  19. Neurophysiological evidence for cerebellar dysfunction in primary focal dystonia.

    NARCIS (Netherlands)

    Teo, J.T.; Warrenburg, B.P.C. van de; Schneider, S.A.; Rothwell, J.C.; Bhatia, K.P.

    2009-01-01

    Recent studies have suggested that there may be functional and structural changes in the cerebellum of patients with adult onset primary focal dystonia. The aim of this study was to establish whether there is any neurophysiological indicator of abnormal cerebellar function, using the classic

  20. The Localizing Value Of Focal Delta Slowing In Temporal Lobe ...

    African Journals Online (AJOL)

    Slow wave EEG had a higher marginal probability than neuropsychological assessment of predicting the focus, and was equally effective as other investigative methods. Conclusion These results suggest that focal temporal delta slowing is useful in the localization of epileptogenic foci. There was no discordance with the ...

  1. Management of HIV-associated focal brain lesions in developing ...

    African Journals Online (AJOL)

    Background. HIV-associated focal brain lesions (FBLs) are caused by opportunistic infections, neoplasms, or cerebrovascular diseases. In developed countries toxoplasma encephalitis (TE) is the most frequent cause followed by primary CNS lymphoma (PCNSL). Guidelines based on these causes have been proposed ...

  2. Quantum-Well Infrared Photodetector (QWIP) Focal Plane Assembly

    Science.gov (United States)

    Jhabvala, Murzy; Jhabvala, Christine A.; Ewin, Audrey J.; Hess, Larry A.; Hartmann, Thomas M.; La, Anh T.

    2012-01-01

    A paper describes the Thermal Infrared Sensor (TIRS), a QWIP-based instrument intended to supplement the Operational Land Imager (OLI) for the Landsat Data Continuity Mission (LDCM). The TIRS instrument is a far-infrared imager operating in the pushbroom mode with two IR channels: 10.8 and 12 microns. The focal plane will contain three 640x512 QWIP arrays mounted on a silicon substrate. The silicon substrate is a custom-fabricated carrier board with a single layer of aluminum interconnects. The general fabrication process starts with a 4-in. (approx.10-cm) diameter silicon wafer. The wafer is oxidized, a single substrate contact is etched, and aluminum is deposited, patterned, and alloyed. This technology development is aimed at incorporating three large-format infrared detecting arrays based on GaAs QWIP technology onto a common focal plane with precision alignment of all three arrays. This focal plane must survive the rigors of flight qualification and operate at a temperature of 43 K (-230 C) for five years while orbiting the Earth. The challenges presented include ensuring thermal compatibility among all the components, designing and building a compact, somewhat modular system and ensuring alignment to very tight levels. The multi-array focal plane integrated onto a single silicon substrate is a new application of both QWIP array development and silicon wafer scale integration. The Invar-based assembly has been tested to ensure thermal reliability.

  3. [Primary focal dystonia: descriptive study of 205 patients].

    Science.gov (United States)

    Bartolomé, F M; Fanjul, S; Cantarero, S; Hernández, J; García Ruiz, P J

    2003-03-01

    To describe the clinical and epidemiologic aspects of different types of focal dystonia. A total of 205 patients with primary focal dystonia were studied retrospectively and the following variables were analyzed: gender, age of onset, age at examination, evolution time, history of trauma, association with other movement disorders, fluctuations of dystonic symptoms as well as a family history of dystonia, Parkinson's disease, tremor, and lefthandedness or stuttering. We compared these variables among the different clinical categories of focal dystonia. Those patients with cranial and laryngeal dystonia were significantly older at the onset of symptoms compared with patients with writer's cramp. Males were more prevalent than females in all categories of focal dystonia except for cranial dystonia. Prior history of trauma and association with tremor were more frequent in patients with cervical dystonia than in those with others dystonic categories. Most patients with cranial, cervical and laryngeal dystonia had fluctuations in the intensity of dystonic symptoms, unlike the patients with writer's cramp. There is a caudo-cranial gradient in age of onset and the age of onset increases as the cranial presentation becomes greater. Females are more prevalent in cranial dystonia and there is a preponderance of males in the dystonias with a lower location. The dystonias with cranial distribution frequently present fluctuations of symptoms during the day. Association with other movement disorders, such as tremor, and prior history of trauma, is common in patients with cervical dystonia.

  4. Focal fibrocartilaginous dysplasia and tibia vara: a case report

    International Nuclear Information System (INIS)

    Cockshott, W.P.; Martin, R.; Friedman, L.; Yuen, M.

    1994-01-01

    A 2-year-old black boy with focal fibrocartilaginous dysplasia is described with illustrations of the typical radiographic appearances supplemented by computed tomographic and magnetic resonance images. Since this rare condition is self-correcting, diagnosis is important so that surgical intervention and biopsy can be avoided and conservative management instituted. (orig.)

  5. Focal fibrocartilaginous dysplasia and tibia vara: a case report.

    Science.gov (United States)

    Cockshott, W P; Martin, R; Friedman, L; Yuen, M

    1994-07-01

    A 2-year-old black boy with focal fibrocartilaginous dysplasia is described with illustrations of the typical radiographic appearances supplemented by computed tomographic and magnetic resonance images. Since this rare condition is self-correcting, diagnosis is important so that surgical intervention and biopsy can be avoided and conservative management instituted.

  6. Focal fibrocartilaginous dysplasia and tibia vara: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Cockshott, W.P. (Dept. of Radiology, McMaster Univ. Medical Centre, Hamilton, ON (Canada)); Martin, R. (Dept. of Orthopedics, McMaster Univ. Medical Centre, Hamilton, ON (Canada)); Friedman, L. (Dept. of Radiology, McMaster Univ. Medical Centre, Hamilton, ON (Canada)); Yuen, M. (Dept. of Radiology, McMaster Univ. Medical Centre, Hamilton, ON (Canada))

    1994-07-01

    A 2-year-old black boy with focal fibrocartilaginous dysplasia is described with illustrations of the typical radiographic appearances supplemented by computed tomographic and magnetic resonance images. Since this rare condition is self-correcting, diagnosis is important so that surgical intervention and biopsy can be avoided and conservative management instituted. (orig.)

  7. Contrast enhanced ultrasound in CT-undetermined focal liver lesions

    DEFF Research Database (Denmark)

    Sandrose, Sebastian; Karstrup, S.; Gerke, Oke

    2016-01-01

    , surgical resection, PET/CT and clinical follow-up. Results: The 78 included patients had 163 undetermined focal liver lesions, mean size 1.1 cm, range 0.1–5.3 cm. There were 18 malignant and 145 benign liver lesions, as defined by the standard of reference. In differentiating between benign vs. malignant...

  8. Automatic test comes to focal plane array production

    Science.gov (United States)

    Skaggs, Frank L.; Barton, T. D.

    1992-08-01

    To meet the needs of military and commercial markets, the infrared focal plane array industry must develop new, effective and low cost methods of fabricating and testing imaging detectors. This paper describes Texas Instruments new concepts in automated testing and cold probe technology as they apply to volume production.

  9. Focal irreversible electroporation as primary treatment for localized prostate cancer

    NARCIS (Netherlands)

    van den Bos, Willemien; Scheltema, Matthijs J.; Siriwardana, Amila R.; Kalsbeek, Anton M. F.; Thompson, James E.; Ting, Francis; Böhm, Maret; Haynes, Anne-Maree; Shnier, Ron; Delprado, Warick; Stricker, Phillip D.

    2017-01-01

    To determine the safety, quality of life (QoL) and short-term oncological outcomes of primary focal IRE for the treatment of localized prostate cancer. To identify potential risk factors for oncological failure. Patients that met both the consensus guidelines on patient criteria and selection

  10. Position sensitive proportional counters as focal plane detectors

    International Nuclear Information System (INIS)

    Ford, J.L.C. Jr.

    1979-01-01

    The rise time and charge division techniques for position decoding with RC-line proportional counters are reviewed. The advantages that these detectors offer as focal plane counters for nuclear spectroscopy performed with magnetic spectrographs are discussed. The theory of operation of proportional counters as position sensing devices is summarized, as well as practical aspects affecting their application. Factors limiting the position and energy resolutions obtainable with a focal plane proportional counter are evaluated and measured position and energy loss values are presented for comparison. Detector systems capable of the multiparameter measurements required for particle identification, background suppression and ray-tracing are described in order to illustrate the wide applicability of proportional counters within complex focal plane systems. Examples of the use of these counters other than with magnetic spectrographs are given in order to demonstrate their usefulness in not only nuclear physics but also in fields such as solid state physics, biology, and medicine. The influence of the new focal plane detector systems on future magnetic spectrograph designs is discussed. (Auth.)

  11. White matter integrity and cerebral network topology in focal epilepsy

    NARCIS (Netherlands)

    Otte, W.M.

    2012-01-01

    Worldwide more than fifty million people suffer from recurrent spontaneous seizures. Seizures are considered to be harmful to the brain and may have adverse long-term behavioral and cognitive consequences in particular in people with focal epilepsies that do not respond to pharmacotherapy.

  12. Mutations in KCNT1 cause a spectrum of focal epilepsies

    Science.gov (United States)

    Møller, Rikke S.; Heron, Sarah E.; Larsen, Line H. G.; Lim, Chiao Xin; Ricos, Michael G.; Bayly, Marta A.; van Kempen, Marjan J. A.; Klinkenberg, Sylvia; Andrews, Ian; Kelley, Kent; Ronen, Gabriel M.; Callen, David; McMahon, Jacinta M.; Yendle, Simone C.; Carvill, Gemma L.; Mefford, Heather C.; Nabbout, Rima; Poduri, Annapurna; Striano, Pasquale; Baglietto, Maria G.; Zara, Federico; Smith, Nicholas J.; Pridmore, Clair; Gardella, Elena; Nikanorova, Marina; Dahl, Hans Atli; Gellert, Pia; Scheffer, Ingrid E.; Gunning, Boudewijn; Kragh-Olsen, Bente; Dibbens, Leanne M.

    2018-01-01

    Summary Autosomal dominant mutations in the sodium-gated potassium channel subunit gene KCNT1 have been associated with two distinct seizure syndromes, nocturnal frontal lobe epilepsy (NFLE) and malignant migrating focal seizures of infancy (MMFSI). To further explore the phenotypic spectrum associated with KCNT1, we examined individuals affected with focal epilepsy or an epileptic encephalopathy for mutations in the gene. We identified KCNT1 mutations in 12 previously unreported patients with focal epilepsy, multifocal epilepsy, cardiac arrhythmia, and in a family with sudden unexpected death in epilepsy (SUDEP), in addition to patients with NFLE and MMFSI. In contrast to the 100% penetrance so far reported for KCNT1 mutations, we observed incomplete penetrance. It is notable that we report that the one KCNT1 mutation, p.Arg398Gln, can lead to either of the two distinct phenotypes, ADNFLE or MMFSI, even within the same family. This indicates that genotype–phenotype relationships for KCNT1 mutations are not straightforward. We demonstrate that KCNT1 mutations are highly pleiotropic and are associated with phenotypes other than ADNFLE and MMFSI. KCNT1 mutations are now associated with Ohtahara syndrome, MMFSI, and nocturnal focal epilepsy. They may also be associated with multifocal epilepsy and cardiac disturbances. PMID:26122718

  13. Differential diagnosis of focal pancreatitis and pancreatic cancer

    NARCIS (Netherlands)

    van Gulik, T. M.; Moojen, T. M.; van Geenen, R.; Rauws, E. A.; Obertop, H.; Gouma, D. J.

    1999-01-01

    The differentiation of focal, chronic pancreatitis (CP) and pancreatic cancer (PAC) poses a diagnostic dilemma. Both conditions may present with the same symptoms and signs. The complexity of differential diagnosis is enhanced because PAC is frequently associated with secondary inflammatory changes

  14. Mutations in KCNT1 cause a spectrum of focal epilepsies

    DEFF Research Database (Denmark)

    Møller, Rikke Steensbjerre; Heron, Sarah E.; Larsen, Line H. G.

    2015-01-01

    Autosomal dominant mutations in the sodium-gated potassium channel subunit gene KCNT1 have been associated with two distinct seizure syndromes, nocturnal frontal lobe epilepsy (NFLE) and malignant migrating focal seizures of infancy (MMFSI). To further explore the phenotypic spectrum associated w...

  15. Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Al-Qaisieh, Bashar [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Mason, Josh, E-mail: joshua.mason@nhs.net [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Bownes, Peter; Henry, Ann [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Dickinson, Louise [Division of Surgery and Interventional Science, University College London, London (United Kingdom); Department of Radiology, Northwick Park Hospital, London North West NHS Trust, London (United Kingdom); Ahmed, Hashim U. [Division of Surgery and Interventional Science, University College London, London (United Kingdom); University College London Hospital, London (United Kingdom); Emberton, Mark [University College London Hospital, London (United Kingdom); Langley, Stephen [St Luke' s Cancer Centre, Guildford (United Kingdom)

    2015-07-15

    Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm{sup 3} was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable

  16. METHOD FOR DETERMINATION OF FOCAL PLANE LOCATION OF FOCUSING COMPONENTS

    Directory of Open Access Journals (Sweden)

    A. I. Ivashko

    2017-01-01

    Full Text Available Mass-production of different laser systems often requires utilization of the focal spot size method for determination of output laser beam spatial characteristics. The main challenge of this method is high accuracy maintenance of a CCD camera beam profiler in the collecting lens focal plane. The aim of our work is development of new method for placing of photodetector array in the collecting lens focal plane with high accuracy.Proposed technique is based on focusing of several parallel laser beams. Determination of the focal plane position requires only longitudinal translation of the CCD-camera to find a point of laser beams intersection. Continuous-wave (CW diode-pumped laser emitting in the spectral region near 1μm was created to satisfy the requirements of the developed technique. Designed microchip laser generates two stigmatic Gaussian beams with automatically parallel beam axes due to independent pumping of different areas of the one microchip crystal having the same cavity mirrors.It was theoretically demonstrated that developed method provides possibility of the lenses focal plane determination with 1 % accuracy. The microchip laser generates two parallel Gaussian beams with divergence of about 10 mrad. Laser output power can be varied in the range of 0.1–1.5 W by changing the pumping laser diode electrical current. The distance between two beam axes can be changed in the range of 0.5–5.0 mm.We have proposed method for determination of positive lens focal plane location by using of CCDcamera and two laser beams with parallel axes without utilization of additional optical devices. We have developed CW longitudinally diode pumped microchip laser emitting in the 1-μm spectral region that can be used in the measuring instrument that doesn’t require precision mechanical components for determination of focal plane location with 1 % accuracy. The overall dimensions of laser head was 70 × 40 × 40 mm3 and maximum power consumption was

  17. Context cue focality influences strategic prospective memory monitoring.

    Science.gov (United States)

    Hunter Ball, B; Bugg, Julie M

    2018-02-12

    Monitoring the environment for the occurrence of prospective memory (PM) targets is a resource-demanding process that produces cost (e.g., slower responding) to ongoing activities. However, research suggests that individuals are able to monitor strategically by using contextual cues to reduce monitoring in contexts in which PM targets are not expected to occur. In the current study, we investigated the processes supporting context identification (i.e., determining whether or not the context is appropriate for monitoring) by testing the context cue focality hypothesis. This hypothesis predicts that the ability to monitor strategically depends on whether the ongoing task orients attention to the contextual cues that are available to guide monitoring. In Experiment 1, participants performed an ongoing lexical decision task and were told that PM targets (TOR syllable) would only occur in word trials (focal context cue condition) or in items starting with consonants (nonfocal context cue condition). In Experiment 2, participants performed an ongoing first letter judgment (consonant/vowel) task and were told that PM targets would only occur in items starting with consonants (focal context cue condition) or in word trials (nonfocal context cue condition). Consistent with the context cue focality hypothesis, strategic monitoring was only observed during focal context cue conditions in which the type of ongoing task processing automatically oriented attention to the relevant features of the contextual cue. These findings suggest that strategic monitoring is dependent on limited-capacity processing resources and may be relatively limited when the attentional demands of context identification are sufficiently high.

  18. Flotillins Regulate Focal Adhesions by Interacting with α-Actinin and by Influencing the Activation of Focal Adhesion Kinase

    Directory of Open Access Journals (Sweden)

    Antje Banning

    2018-04-01

    Full Text Available Cell–matrix adhesion and cell migration are physiologically important processes that also play a major role in cancer spreading. In cultured cells, matrix adhesion depends on integrin-containing contacts such as focal adhesions. Flotillin-1 and flotillin-2 are frequently overexpressed in cancers and are associated with poor survival. Our previous studies have revealed a role for flotillin-2 in cell–matrix adhesion and in the regulation of the actin cytoskeleton. We here show that flotillins are important for cell migration in a wound healing assay and influence the morphology and dynamics of focal adhesions. Furthermore, anchorage-independent growth in soft agar is enhanced by flotillins. In the absence of flotillins, especially flotillin-2, phosphorylation of focal adhesion kinase and extracellularly regulated kinase is diminished. Flotillins interact with α-actinin, a major regulator of focal adhesion dynamics. These findings are important for understanding the molecular mechanisms of how flotillin overexpression in cancers may affect cell migration and, especially, enhance metastasis formation.

  19. Resveratrol inhibits the intracellular calcium increase and angiotensin/endothelin system activation induced by soluble uric acid in mesangial cells

    Energy Technology Data Exchange (ETDEWEB)

    Albertoni, G.; Schor, N. [Divisão de Nefrologia, Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2014-10-24

    Resveratrol (Resv) is natural polyphenol found in grapes. This study evaluated the protective effect of Resv against the effects of uric acid (UA) in immortalized human mesangial cells (ihMCs). ihMCs were preincubated with Resv (12.5 µM) for 1 h and treated with UA (10 mg/dL) for 6 or 12 h. The intracellular calcium concentration [Ca{sup 2+}]i was quantified by fluorescence using flow cytometry. Angiotensinogen (AGT) and pre-pro endothelin-1 (ppET-1) mRNA were assayed by quantitative real-time RT-PCR. Angiotensin II (AII) and endothelin-1 (ET-1) were assayed by ELISA. UA significantly increased [Ca{sup 2+}]i. Pre-incubation with Resv significantly reduced the change in [Ca{sup 2+}]i induced by UA. Incubation with UA for 6 or 12 h also increased AGT mRNA expression and AII protein synthesis. Resv blunted these increases in AGT mRNA expression and AII protein. Incubation with UA in the ihMCs increased ppET-1 expression and ET-1 protein synthesis at 6 and 12 h. When ihMCs were pre-incubated with Resv, UA had a significantly diminished effect on ppET-1 mRNA expression and ET-1 protein synthesis at 6 and 12 h, respectively. Our results suggested that UA triggers reactions including AII and ET-1 production in mesangial cells. The renin-angiotensin system may contribute to the pathogenesis of renal function and chronic kidney disease. Resv can minimize the impact of UA on AII, ET-1 and the increase of [Ca{sup 2+}]i in mesangial cells, suggesting that, at least in part, Resv can prevent the effects of soluble UA in mesangial cells.

  20. [Efficacy of topical ketorolac for improving visual function after photocoagulation in diabetic patients with focal macular edema].

    Science.gov (United States)

    Razo Blanco-Hernández, Dulce Milagros; Lima-Gómez, Virgilio; Asbun-Bojalil, Juan

    2014-01-01

    Photocoagulation reduces the incidence of visual loss in diabetic patients with focal macular edema, but it can induce it for Efficacy of topical ketorolac for improving visual function after photocoagulation in diabetic patients with focal macular edema 6 weeks after treatment and produces visual improvement in some cases. Topical ketorolac may reduce the inflammation caused by photocoagulation and improve visual outcome. To determine the efficacy of topical ketorolac for improving visual function after photocoagulation in diabetic patients with focal macular edema. An experimental, comparative, prospective, longitudinal study in diabetic patients with focal macular edema was conducted. Eyes were randomized into two groups of topical treatment for 3 weeks after photocoagulation (A: ketorolac, B: placebo). Best corrected visual acuity before and after treatment was compared in each group (paired t test), and the proportion of eyes with visual improvement was compared between groups (χ(2)). The evaluation was repeated after stratifying for initial visual acuity (≥ 0.5, < 0.5). There were 105 eyes included. In group A (n= 46) mean visual acuity changed from 0.50 to 0.58 (p= 0.003), and from 0.55 to 0.55 in group B (n= 59, p= 0.83); mean percent change was 22.3% in group A and 3.5% in group B (p= 0.03). Visual improvement was identified in 25 eyes from group A (54.3%) and 19 from group B (32.2%, p= 0.019, RR 1.65); the difference only persisted when initial visual acuity was ≥ 0.5 (10 [40%], group A, 5 [14.7%], group B, p= 0.02, RR 2.72). Topical ketorolac was more effective than placebo to improve best corrected visual acuity in diabetic patients with focal macular edema.

  1. LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats

    International Nuclear Information System (INIS)

    Fang, T.; Zhou, D.; Lu, L.; Tong, X.; Wu, J.; Yi, L.

    2016-01-01

    Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases

  2. LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats

    Energy Technology Data Exchange (ETDEWEB)

    Fang, T.; Zhou, D.; Lu, L.; Tong, X.; Wu, J.; Yi, L. [Department of Neurology, Shenzhen Hospital, Peking University, Shenzhen (China)

    2016-08-01

    Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases.

  3. The flexible engagement of monitoring processes in non-focal and focal prospective memory tasks with salient cues.

    Science.gov (United States)

    Hefer, Carmen; Cohen, Anna-Lisa; Jaudas, Alexander; Dreisbach, Gesine

    2017-09-01

    Prospective memory (PM) refers to the ability to remember to perform a delayed intention. Here, we aimed to investigate the ability to suspend such an intention and thus to confirm previous findings (Cohen, Gordon, Jaudas, Hefer, & Dreisbach, 2016) demonstrating the ability to flexibly engage in monitoring processes. In the current study, we presented a perceptually salient PM cue (bold and red) to rule out that previous findings were limited to non-salient and, thus, easy to ignore PM cues. Moreover, we used both a non-focal (Experiment 1) and a focal PM (Experiment 2) cue. In both Experiments, three groups of participants performed an Eriksen flanker task as an ongoing task with an embedded PM task (they had to remember to press the F1 key if a pre-specified cue appeared). Participants were assigned to either a control condition (performed solely the flanker task), a standard PM condition (performed the flanker task along with the PM task), or a PM delayed condition (performed the flanker task but were instructed to postpone their PM task intention). The results of Experiment 1 with the non-focal PM cue closely replicated those of Cohen et al. (2016) and confirmed that participants were able to successfully postpone the PM cue intention without additional costs even when the PM cue was a perceptually salient one. However, when the PM cue was focal (Experiment 2), it was much more difficult for participants to ignore it as evidenced by commission errors and slower latencies on PM cue trials. In sum, results showed that the focality of the PM cue plays a more crucial role in the flexibility of the monitoring process whereas the saliency of the PM cue does not. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1.

    Directory of Open Access Journals (Sweden)

    Kiminori Sada

    Full Text Available We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs, cellular hypoxia increased after incubation with high glucose (HG. A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1, a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.

  5. Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: a finite element simulation study

    Science.gov (United States)

    Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

    2011-02-01

    We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced the maximum electric field of 2.1-2.5 V cm-1 and 1.1-2.2 V cm-1 in the brain, corresponding to 6.2-7.2 times and 1.2-2.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much larger with ECT (up to 100%) than with MST (up to 8.2%). MST with the double-cone coil was the most focal, and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800-900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects.

  6. Natural-focal diseases: mapping experience in Russia.

    Science.gov (United States)

    Malkhazova, Svetlana M; Mironova, Varvara A; Kotova, Tatiana V; Shartova, Natalia V; Orlov, Dmitry S

    2014-06-14

    Natural-focal diseases constitute a serious hazard for human health. Agents and vectors of such diseases belong to natural landscapes. The aim of this study is to identify the diversity and geography of natural-focal diseases in Russia and to develop cartographic approaches for their mapping, including mathematical-cartographical modeling. Russian medico-geographical mapping of natural-focal diseases is highly developed regionally and locally but extremely limited at the national level. To solve this problem, a scientific team of the Faculty of Geography at Lomonosov Moscow State University has developed and implemented a project of a medico-geographical Atlas of Russia "Natural-Focal Diseases". The mapping is based on medical statistics data. The Atlas contains a series of maps on disease incidence, long-term dynamics of disease morbidity, etc. In addition, other materials available to the authors were used: mapping of the natural environment, field data, archival materials, analyzed satellite images, etc. The maps are processed using ArcGIS (ESRI) software application. Different methods of rendering of mapped phenomena are used (geographical ranges, diagrams, choropleth maps etc.). A series of analytical, integrated, and synthetic maps shows disease incidence in the population at both the national and regional levels for the last 15 years. Maps of the mean annual morbidity of certain infections and maps of morbidity dynamics and nosological profiles allow for a detailed analysis of the situation for each of 83 administrative units of the Russian Federation. The degree of epidemic hazard in Russia by natural-focal diseases is reflected in a synthetic medico-geographical map that shows the degree of epidemic risks due to such diseases in Russia and allows one to estimate the risk of disease manifestation in a given region. This is the first attempt at aggregation and public presentation of diverse and multifaceted information about natural-focal diseases in Russia

  7. CT and ERCP findings of chronic focal pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee Soo; Lee, Jong Tae; Yoo, Hyung Sik; Kim, Eun Kyeong [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    1996-10-01

    To evaluate the major radiologic features of chronic focal pancreatitis in various imaging studies, with special emphasis on CT and ERCP findings. From 1991 to 1995, twelve patients were pathologically proved to be suffering from focal chronic pancreatitis after pancreatico-duodenectomy;for retrospective evaluation, imaging studies were available for eight(seven men, one woman;mean age 58.9{+-}6.6, range 47 to 67). Clinical, surgical, and radiological findings, including CT(n=8), ultrasound(n=7), ERCP(n=8) and UGI(n=3) were analysed. Seven male patients had suffered from chronic alcoholism for between 20 and 50 years. Serum bilirubin levels were normal in eight patients and alkaline phosphatase levels were normal in seven patients. Serum CA 19-9 levels were normal in all five patients who had undergone preoperative evaluation. Seven patients(87.5%) showed focal enlargement without definable margin on CT, and five of the six lesions detectable on ultrasound(83.3%) were ill defined hypoechoic nodules. Dilated side branches within lesions were seen in five of eight patients(83.3%) on CT and ERCP. Double duct signs were observed in siven(87.5%) patients, and dilated intrahepatic ducts in six(75%), with diameters ranging from 5 to 8mm(average:5.42{+-}1.96mm). The average ratio of pancreatic duct caliber to gland width was 0.33{+-}0.19. None of the patients had calcification within the lesion and one case showed intraductal calcification. None showed perivascular fat obliteration around the superior mesenteric artery or celiac axis. The average biductal distance between abnormal common bile duct and the immediately adjacent pancreatic duct was 4.0{+-}1.15mm. One of three cases who under went a UGI examination showed severe luminal narrowing and mucosal thickening in the second protion of the duodenum, another showed double contour, and the other merely showed widening of the C-loop of the duodenum. Chronic focal pancreatitis mostly demonstrated ill defined focal

  8. CT and ERCP findings of chronic focal pancreatitis

    International Nuclear Information System (INIS)

    Kim, Hee Soo; Lee, Jong Tae; Yoo, Hyung Sik; Kim, Eun Kyeong

    1996-01-01

    To evaluate the major radiologic features of chronic focal pancreatitis in various imaging studies, with special emphasis on CT and ERCP findings. From 1991 to 1995, twelve patients were pathologically proved to be suffering from focal chronic pancreatitis after pancreatico-duodenectomy;for retrospective evaluation, imaging studies were available for eight(seven men, one woman;mean age 58.9±6.6, range 47 to 67). Clinical, surgical, and radiological findings, including CT(n=8), ultrasound(n=7), ERCP(n=8) and UGI(n=3) were analysed. Seven male patients had suffered from chronic alcoholism for between 20 and 50 years. Serum bilirubin levels were normal in eight patients and alkaline phosphatase levels were normal in seven patients. Serum CA 19-9 levels were normal in all five patients who had undergone preoperative evaluation. Seven patients(87.5%) showed focal enlargement without definable margin on CT, and five of the six lesions detectable on ultrasound(83.3%) were ill defined hypoechoic nodules. Dilated side branches within lesions were seen in five of eight patients(83.3%) on CT and ERCP. Double duct signs were observed in siven(87.5%) patients, and dilated intrahepatic ducts in six(75%), with diameters ranging from 5 to 8mm(average:5.42±1.96mm). The average ratio of pancreatic duct caliber to gland width was 0.33±0.19. None of the patients had calcification within the lesion and one case showed intraductal calcification. None showed perivascular fat obliteration around the superior mesenteric artery or celiac axis. The average biductal distance between abnormal common bile duct and the immediately adjacent pancreatic duct was 4.0±1.15mm. One of three cases who under went a UGI examination showed severe luminal narrowing and mucosal thickening in the second protion of the duodenum, another showed double contour, and the other merely showed widening of the C-loop of the duodenum. Chronic focal pancreatitis mostly demonstrated ill defined focal enlargement and

  9. In vivo inhibition of incorporation of (U-/sup 14/C)glucose into proteins in experimental focal epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Coutinho-Netto, J.; Boyar, M.M.; Abdul-Ghani, A.S.; Bradford, H.F.

    1982-08-01

    The in vivo incorporation of (/sup 14/C) from (U-/sup 14/C)-glucose into rat brain proteins from different cortical areas was examined in three different experimental focal epilepsies: cobalt, freeze-lesions, and tityustoxin. When (U-/sup 14/C)-glucose was injected intraperitoneally into awake and unrestrained animals with marked signs of epileptic hyperactivity, the inhibition of incorporation of (/sup 14/C)-amino acids into trichloracetic acid (TCA)-insoluble proteins was highest in the focal (sensorimotor) area when compared with distant regions (approx. 60%), but less when compared with the contralateral (sensorimotor) region (approx. 23%). Greatly decreased incorporation caused by both cobalt and freeze-lesion-induced epilepsies was also observed in the contralateral area when a comparison was made with distant regions (approx. 50%), but there were no significant differences in protein-specific radioactivity between the different distant areas.

  10. Collapsing focal segmental glomerulosclerosis following long-term treatment with oral ibandronate: case report and review of literature

    International Nuclear Information System (INIS)

    Jia, Ning; Cormack, Fionnuala C.; Xie, Bin; Shiue, Zita; Najafian, Behzad; Gralow, Julie R.

    2015-01-01

    Renal toxicity has been reported with bisphosphonates such as pamidronate and zolidronate but not with ibandronate, in the treatment of breast cancer patients with bone metastasis. One of the patterns of bisphosphonate-induced nephrotoxicity is focal segmental glomerulosclerosis (FSGS) or its morphological variant, collapsing focal segmental glomerulosclerosis (CFSGS). We describe a breast cancer patient who developed heavy proteinuria (protein/creatinine ratio 9.1) and nephrotic syndrome following treatment with oral ibandronate for 29 months. CFSGS was proven by biopsy. There was no improvement 1 month after ibandronate was discontinued. Prednisone and tacrolimus were started and she experienced a decreased in proteinuria. In patient who develops ibandronate-associated CFSGS, proteinuria appears to be at least partially reversible with the treatment of prednisone and/or tacrolimus if the syndrome is recognized early and ibandronate is stopped

  11. Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

    Science.gov (United States)

    Wattanathorn, Jintanaporn; Jittiwat, Jinatta; Tongun, Terdthai; Muchimapura, Supaporn; Ingkaninan, Kornkanok

    2011-01-01

    Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia. PMID:21197427

  12. Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2011-01-01

    Full Text Available Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO. Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA, superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GSH-Px in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia.

  13. Neuroprotective effect of curcumin on transient focal cerebral ischemia in rats.

    Science.gov (United States)

    Zhao, Jing; Zhao, Yong; Zheng, Weiping; Lu, Yuyu; Feng, Gang; Yu, Shanshan

    2008-09-10

    Curcumin, a member of the curcuminoid family of compounds, is a yellow colored phenolic pigment obtained from the powdered rhizome of C. longa Linn. Recent studies have demonstrated that curcumin has protective effects against cerebral ischemia/reperfusion injury. However, little is known about its mechanism. Hence, in the present study the neuroprotective potential of curcumin was investigated in middle cerebral artery occlusion (MCAO) induced focal cerebral IR injury. Administration of curcumin 100 and 300 mg/kg i.p. 60 min after MCAO significantly diminished infarct volume, and improved neurological deficit in a dose-dependent manner. Nissl staining showed that the neuronal injury was significantly improved after being treated with curcumin. Curcumin significantly decreased the expression of caspase-3 protein. A higher number of TUNEL-positive cells were found in the vehicle group, but they were significantly decreased in the treated group. Taken together, these results suggest that the neuroprotective potentials of curcumin against focal cerebral ischemic injury are, at least in part, ascribed to its anti-apoptotic effects.

  14. Oral focal epithelial hyperplasia: report of three cases.

    Science.gov (United States)

    Ghalayani, Parichehr; Tavakoli, Payam; Eftekhari, Mehdi; Haghighi, Mohammad Akhondzadeh

    2015-01-01

    Focal epithelial hyperplasia or Heck's disease is an infrequent asymptomatic condition caused by human papillomavirus types 13 or 32 affecting the mucous membrane of the mouth and is commonly seen in young individuals. Firstly, it was described in Indians and Eskimos, but it exists in various populations. We present three cases of Heck's disease in an Afghan immigrant family group living in Iran that seem to have familial predominance. The disease was identified as oral focal epithelial hyperplasia on the basis of histopathologic and clinical findings. The lesions were reduced significantly after 4 months of good oral hygiene. Dentists should be familiar with the clinical manifestations of these types of lesions that affect the oral cavity. In fact, histopathologic assessment and clinical observation are necessary to establish the diagnosis.

  15. Uncooled infrared focal plane array imaging in China

    Science.gov (United States)

    Lei, Shuyu

    2015-06-01

    This article reviews the development of uncooled infrared focal plane array (UIFPA) imaging in China in the past decade. Sensors based on optical or electrical read-out mechanism were developed but the latter dominates the market. In resistive bolometers, VOx and amorphous silicon are still the two major thermal-sensing materials. The specifications of the IRFPA made by different manufactures were collected and compared. Currently more than five Chinese companies and institutions design and fabricate uncooled infrared focal plane array. Some devices have sensitivity as high as 30 mK; the largest array for commercial products is 640×512 and the smallest pixel size is 17 μm. Emphasis is given on the pixel MEMS design, ROIC design, fabrication, and packaging of the IRFPA manufactured by GWIC, especially on design for high sensitivities, low noise, better uniformity and linearity, better stabilization for whole working temperature range, full-digital design, etc.

  16. Focal points and principal solutions of linear Hamiltonian systems revisited

    Science.gov (United States)

    Šepitka, Peter; Šimon Hilscher, Roman

    2018-05-01

    In this paper we present a novel view on the principal (and antiprincipal) solutions of linear Hamiltonian systems, as well as on the focal points of their conjoined bases. We present a new and unified theory of principal (and antiprincipal) solutions at a finite point and at infinity, and apply it to obtain new representation of the multiplicities of right and left proper focal points of conjoined bases. We show that these multiplicities can be characterized by the abnormality of the system in a neighborhood of the given point and by the rank of the associated T-matrix from the theory of principal (and antiprincipal) solutions. We also derive some additional important results concerning the representation of T-matrices and associated normalized conjoined bases. The results in this paper are new even for completely controllable linear Hamiltonian systems. We also discuss other potential applications of our main results, in particular in the singular Sturmian theory.

  17. Focal sparing around the gallbladder in fatty liver

    International Nuclear Information System (INIS)

    Chen, Kemin; Hiramatsu, Yoshihiro; Yunoki, Masanori; Hirano, Yoko

    1989-01-01

    In evaluating fatty liver with CT, the residual normal liver tissues without fat deposits are occasionally detected on CT as high attenuation regions, especially surrounding the gallbladder. This study examined the incidence of this phenomenon in terms of the diagnostic value of CT in fatty liver. Fifty-seven patients with fatty liver were examined with CT. The incidence of focal sparing area was the highest in the gallbladder bed (42/57, 74%), followed by the interlobar fissure or subcapsular area (13, 23%), quadrate lobe (8, 14%), caudate lobe (2, 4%), and right lobe (one, 1.8%). These CT appearances were of spot, band, ring, and the mixed type. In 38 patients, fatty liver was too moderate to be detected without CT attenuation numbers. Among them, 27 patients (71%) had focal sparing area surrounding the gallbladder. This CT appearance seemed to be of significance in preventing the missing of moderate fatty liver. (Namekawa, K)

  18. Segmented focal plane detector for light and heavy ions

    International Nuclear Information System (INIS)

    Wolfs, F.L.H.; Bryan, D.C.; Kurz, K.L.; Herrick, D.M.; Perera, P.A.A.; White, C.A.

    1992-01-01

    A segmented focal plane detector for an Enge split-pole spectrograph has been developed for the study of breakup reactions at very low relative energies. It consists of a 61 cm long segmented position-sensitive parallel plate avalanche counter backed by a large Bragg curve detector. A segmented plastic scintillator is mounted behind the anode of the Bragg curve detector and is used for particle identification of low-ionizing particles. The dead space between the two sections of the focal plane detector is 2.5 mm. The intrinsic position resolution of the detector is 1 mm. The intrinsic energy resolution depends on the energy of the incident ion and can be as good as 0.55%. The nuclear charge and mass resolutions are 0.3 e and 0.3 u, respectively. (orig.)

  19. Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration.

    Science.gov (United States)

    Wu, Jui-Chung; Chen, Yu-Chen; Kuo, Chih-Ting; Wenshin Yu, Helen; Chen, Yin-Quan; Chiou, Arthur; Kuo, Jean-Cheng

    2015-12-18

    Directed cell migration requires dynamical control of the protein complex within focal adhesions (FAs) and this control is regulated by signaling events involving tyrosine phosphorylation. We screened the SH2 domains present in tyrosine-specific kinases and phosphatases found within FAs, including SRC, SHP1 and SHP2, and examined whether these enzymes transiently target FAs via their SH2 domains. We found that the SRC_SH2 domain and the SHP2_N-SH2 domain are associated with FAs, but only the SRC_SH2 domain is able to be regulated by focal adhesion kinase (FAK). The FAK-dependent association of the SRC_SH2 domain is necessary and sufficient for SRC FA targeting. When the targeting of SRC into FAs is inhibited, there is significant suppression of SRC-mediated phosphorylation of paxillin and FAK; this results in an inhibition of FA formation and maturation and a reduction in cell migration. This study reveals an association between FAs and the SRC_SH2 domain as well as between FAs and the SHP2_N-SH2 domains. This supports the hypothesis that the FAK-regulated SRC_SH2 domain plays an important role in directing SRC into FAs and that this SRC-mediated FA signaling drives cell migration.

  20. A focal plane detector for both light and heavy ions

    International Nuclear Information System (INIS)

    Ophel, T.R.; Johnston, A.

    1978-05-01

    The characteristics of a multi-element, ionization-type focal plane detector with an effective length of 53 cm have been evaluated for various ions ranging between protons and 32 S. The position resolution obtained is typically 1 mm. Excellent energy (0.49% for 16 O) and angular resolution (0.2 degrees with respect to beam direction for 7 Li) have been obtained enabling clean separation of ion species at essentially full angular acceptance of a split-pole spectrograph

  1. Perampanel for focal epilepsy: insights from early clinical experience

    OpenAIRE

    Trinka, E.; Steinhoff, B. J.; Nikanorova, M.; Brodie, M. J.

    2015-01-01

    Perampanel is approved for adjunctive therapy of focal epilepsy with or without secondarily generalized seizures in patients aged >12 years. This narrative review uses real-world and clinical trial data to elucidate perampanel's role in the clinic. Audit data show good tolerability with perampanel and higher freedom-from-seizure rates in elderly vs younger patients. When using perampanel in elderly patients, special attention should be given to comorbidities and co-medication to avoid potenti...

  2. Primary Focal Dystonia: Evidence for Distinct Neuropsychiatric and Personality Profiles

    OpenAIRE

    2009-01-01

    Abstract Background: Primary focal dystonia (PFD) is characterized by motor symptoms. Frequent co-occurrence of abnormal mental conditions has been mentioned for decades but is less well defined. We evaluated prevalence rates of psychiatric disorders, personality disorders and traits in a large cohort of PFD patients. Methods: Prevalence rates of clinical psychiatric diagnoses in 86 PFD patients were compared to a population-based sample (N=3943) using a multiple regress...

  3. The extracellular matrix and altered diffusion in focal cortical dysplasia

    Czech Academy of Sciences Publication Activity Database

    Homola, Aleš; Vargová, Lýdia; Cicanič, Michal; Zámečník, J.; Marusič, P.; Kršek, P.; Syková, Eva

    2011-01-01

    Roč. 59, S1 (2011), S106-S106 ISSN 0894-1491. [European meeting on Glia l Cells in Health and Disease /10./. 13.09.2011-17.09.2011, Prague] R&D Projects: GA MŠk 1M0538; GA ČR GA309/09/1597 Institutional research plan: CEZ:AV0Z50390703 Keywords : focal cortical dysplasia * diffusion * extracellular matrix Subject RIV: FH - Neurology

  4. Atypical Focal Osteomyelitis as Initial Manifestation of AIDS

    OpenAIRE

    A. Akiki; Y. Bilde

    2011-01-01

    Persistent pain development after a skeletal contusion rarely poses the diagnosis of osteomyelitis. We report the case of a fibular head contusion as an initial manifestation of a focal abscess development in a healthy young patient. The traditional treatment of surgical drainage revealed the presence of an atypical Mycobacterium haemophilum isolates in the abscess. This lead to further investigations that concluded and established the diagnosis of AIDS. Conclusion. Isolation of an atypical M...

  5. Explaining focal points: Cognitive hierarchy theory versus team reasoning

    OpenAIRE

    Bardsley, Nicholas; Mehta, Judith; Starmer, Chris; Sugden, Robert

    2008-01-01

    This paper reports experimental tests of two alternative explanations of how players use focal points to select equilibria in one-shot coordination games. Cognitive hierarchy theory explains coordination as the result of common beliefs about players’ pre-reflective inclinations towards the relevant strategies; the theory of team reasoning explains it as the result of the players’ using a non-standard form of reasoning. We report two experiments. One finds strong support for team reasoning; th...

  6. Focal epilepsy with ictal abdominal pain: a case report

    OpenAIRE

    Cerminara, Caterina; El Malhany, Nadia; Roberto, Denis; Curatolo, Paolo

    2013-01-01

    Focal epilepsy with ictal abdominal pain is an unusual partial epilepsy characterized by paroxysmal episodes of abdominal or visceral pain, disturbance of awareness and electroencephalographic abnormalities. We describe a new case of ictal abdominal pain in which gastrointestinal complaints were the only manifestation of seizures and review the previously described pediatric patients. In our patient clinical findings, ictal EEG abnormalities, and a good response to antiepileptic drugs allowed...

  7. Seizure ending signs in patients with dyscognitive focal seizures.

    Science.gov (United States)

    Gavvala, Jay R; Gerard, Elizabeth E; Macken, Mícheál; Schuele, Stephan U

    2015-09-01

    Signs indicating the end of a focal seizure with loss of awareness and/or responsiveness but without progression to focal or generalized motor symptoms are poorly defined and can be difficult to determine. Not recognizing the transition from ictal to postictal behaviour can affect seizure reporting accuracy by family members and may lead to delayed or a lack of examination during EEG monitoring, erroneous seizure localization and inadequate medical intervention for prolonged seizure duration. Our epilepsy monitoring unit database was searched for focal seizures without secondary generalization for the period from 2007 to 2011. The first focal seizure in a patient with loss of awareness and/or responsiveness and/or behavioural arrest, with or without automatisms, was included. Seizures without objective symptoms or inadequate video-EEG quality were excluded. A total of 67 patients were included, with an average age of 41.7 years. Thirty-six of the patients had seizures from the left hemisphere and 29 from the right. All patients showed an abrupt change in motor activity and resumed contact with the environment as a sign of clinical seizure ending. Specific ending signs (nose wiping, coughing, sighing, throat clearing, or laughter) were seen in 23 of 47 of temporal lobe seizures and 7 of 20 extra-temporal seizures. Seizure ending signs are often subtle and the most common finding is a sudden change in motor activity and resumption of contact with the environment. More distinct signs, such as nose wiping, coughing or throat clearing, are not specific to temporal lobe onset. A higher proportion of seizures during sleep went unexamined, compared to those during wakefulness. This demonstrates that seizure semiology can be very subtle and arousals from sleep during monitoring should alert staff. Patient accounts of seizure frequency appear to be unreliable and witness reports need to be taken into account. [Published with video sequences].

  8. Intracoronary infusion of catecholamines causes focal arrhythmias in pigs.

    Science.gov (United States)

    Doppalapudi, Harish; Jin, Qi; Dosdall, Derek J; Qin, Hao; Walcott, Gregory P; Killingsworth, Cheryl R; Smith, William M; Ideker, Raymond E; Huang, Jian

    2008-09-01

    Acute ischemia causes myriad changes including increased catecholamines. We tested the hypothesis that elevated catecholamines alone are arrhythmogenic. A 504 electrode sock was placed over both ventricles in six open-chest pigs. During control infusion of saline through a catheter in the left anterior descending coronary artery (LAD), no sustained arrhythmias occurred, and the refractory period estimated by the activation recovery interval (ARI) was 175 +/- 14 ms in the LAD bed below the catheter. After infusion of isoproterenol at 0.1 microg/kg/min through the catheter, the ARI in this bed was significantly reduced to 109 +/- 10 ms. A sharp gradient of refractoriness of 43 +/- 10 ms was at the border of the perfused bed. Sustained monomorphic ventricular tachycardia occurred after drug infusion in the perfused bed or near its boundary in all animals with a cycle length of 329 +/- 26 ms and a focal origin. The maximum slope of the ARI restitution curve at the focal origins of the tachyarrhythmias was always <1 (0.62 +/- 0.15). Similar results with a focal arrhythmia origin occurred in two additional pigs in which intramural mapping was performed with 36 plunge needle electrodes in the left ventricular perfused bed. Regional elevation of a catecholamine, which is one of the alterations produced by acute ischemia, can by itself cause tachyarrhythmias. These arrhythmias are closely associated with a shortened refractory period and a large gradient of the spatial distribution of refractoriness but not with a steep restitution curve.

  9. [A case of focal epilepsy manifesting multiple psychiatric auras].

    Science.gov (United States)

    Ezura, Michinori; Kakisaka, Yosuke; Jin, Kazutaka; Kato, Kazuhiro; Iwasaki, Masaki; Fujikawa, Mayu; Aoki, Masashi; Nakasato, Nobukazu

    2015-01-01

    We present a case of epilepsy with multiple types of focal seizures that were misdiagnosed as psychiatric disorders. A 20-year-old female patient presented with a variety of episodes, including loss of consciousness, deja vu, fear, delusion of possession, violent movements, and generalized convulsions. Each of these symptoms appeared in a stereotypic manner. She was initially diagnosed with a psychiatric disorder and treated with psychoactive medications, which had no effect. Long-term video electroencephalography revealed that her episodes of violent movement with impaired consciousness and secondarily generalized seizure were epileptic events originating in the right hemisphere. High-field brain magnetic resonance imaging for detecting subtle lesions revealed bilateral lesions from periventricular nodular heterotopia. Her final diagnosis was right hemispheric focal epilepsy. Carbamazepine administration was started, which successfully controlled all seizures. The present case demonstrates the pitfall of diagnosing focal epilepsy when it presents with multiple types of psychiatric aura. Epilepsy should thus be included in differential diagnoses, considering the stereotypic nature of symptoms, to avoid misdiagnosis.

  10. How to diagnose and treat focal therapy failure and recurrence?

    Science.gov (United States)

    Barret, Eric; Harvey-Bryan, Kadi-Ann; Sanchez-Salas, Rafael; Rozet, Francois; Galiano, Marc; Cathelineau, Xavier

    2014-05-01

    Focal therapy presents an alternative option for disease-targeted therapy while preserving erectile and urinary function without compromising oncological outcome. Such treatment, which preserves normal prostate parenchyma, presents a clinical challenge to the urologist, as typical disease surveillance parameters are not as reliable in post-ablation follow-up. We propose an integrated approach to post-ablation surveillance to identify treatment failure as well as recurrence. Post-ablation prostate-specific antigen kinetics, imaging based on multiparametric MRI and control biopsies are the tools currently used to follow patients after focal therapy. Good treatment response is indicated by a negative control biopsy, absence of persistent lesion on post-treatment imaging and a reduction in prostate-specific antigen of at least 50%. When histological evidence of therapeutic failure or recurrence is present, different options of management may be proposed to the patient including active surveillance, focal salvage therapy or radical salvage treatment, depending on the characteristics of the lesion found. A recommended post-ablation surveillance protocol is presented as well as a discussion of management strategies based on the data currently available.

  11. Focal lesions in the central nervous system: stereotaxic radioneurosurgery

    International Nuclear Information System (INIS)

    Fabrikant, J.I.; Budinger, T.f.; Hosobuchi, Y.; Born, J.L.; Tobias, C.A.

    1981-01-01

    The application of heavy-ion beams for fundamental and applied brain research has unusual potential. Methods are being developed in our laboratory for producing focal lesions in the central nervous system (e.g., the hypothalamus, thalamus, pituitary gland) to investigate nerve pathways and neuroendocrine responses, and for treating certain pathological disorders of the brain with stereotaxic Bragg peak heavy-ion radiosurgery. Studies in animals are demonstrating the value of this neuroscience tool for investigating mammalian brain response to induction of discrete focal lesions in the hypothalamus or in the cerebral cortex. These studies are also elucidating the neuroendocrinological response follwing ablation of various portions of the midbrain, without requiring complex neurosurgical preparations. Clinical studies are demonstrating the feasibility of stereotaxic neurological radiosurgery for treating certain inoperable vascular disorders of the brain [e.g., arteriovenous malformations (AVM), internal carotid artery-cavernous sinus fistulas and other cerebrovascular disorders] in patients who are already demonstrating progressive neurological deficit. Further applications of focal lesion production with the Bragg ionization peak can be extended to include localized radiation to centers of the brain and spinal cord for treatment of such disorders as Parkinson's disease, pituitary microadenomas, acoustic neuromas, and the control of pain. The eventual application of radioactive beams will provide accurate localization of the stopping points of the beam, thereby making it feasible to stop the beam accurately at a defined depth within the central nervous system

  12. A Micro-Thermal Sensor for Focal Therapy Applications

    Science.gov (United States)

    Natesan, Harishankar; Hodges, Wyatt; Choi, Jeunghwan; Lubner, Sean; Dames, Chris; Bischof, John

    2016-02-01

    There is an urgent need for sensors deployed during focal therapies to inform treatment planning and in vivo monitoring in thin tissues. Specifically, the measurement of thermal properties, cooling surface contact, tissue thickness, blood flow and phase change with mm to sub mm accuracy are needed. As a proof of principle, we demonstrate that a micro-thermal sensor based on the supported “3ω” technique can achieve this in vitro under idealized conditions in 0.5 to 2 mm thick tissues relevant to cryoablation of the pulmonary vein (PV). To begin with “3ω” sensors were microfabricated onto flat glass as an idealization of a focal probe surface. The sensor was then used to make new measurements of ‘k’ (W/m.K) of porcine PV, esophagus, and phrenic nerve, all needed for PV cryoabalation treatment planning. Further, by modifying the sensor use from traditional to dynamic mode new measurements related to tissue vs. fluid (i.e. water) contact, fluid flow conditions, tissue thickness, and phase change were made. In summary, the in vitro idealized system data presented is promising and warrants future work to integrate and test supported “3ω” sensors on in vivo deployed focal therapy probe surfaces (i.e. balloons or catheters).

  13. Fast multifrequency focal beam analysis for 3D seismic acquisition geometry

    NARCIS (Netherlands)

    Wei, W.; Fu, L.; Blacquiere, G.

    2012-01-01

    A method for the efficient computation of multifrequency focal beams for 3D seismic acquisition geometry analysis has been developed. By computing them for all the frequency components of seismic data, single-frequency focal beams can be extended to multifrequency focal beams. However, this

  14. Comprehensive Survey on Improved Focality and Penetration Depth of Transcranial Magnetic Stimulation Employing Multi-Coil Arrays

    Directory of Open Access Journals (Sweden)

    Xile Wei

    2017-11-01

    Full Text Available Multi-coil arrays applied in transcranial magnetic stimulation (TMS are proposed to accurately stimulate brain tissues and modulate neural activities by an induced electric field (EF. Composed of numerous independently driven coils, a multi-coil array has alternative energizing strategies to evoke EFs targeting at different cerebral regions. To improve the locating resolution and the stimulating focality, we need to fully understand the variation properties of induced EFs and the quantitative control method of the spatial arrangement of activating coils, both of which unfortunately are still unclear. In this paper, a comprehensive analysis of EF properties was performed based on multi-coil arrays. Four types of planar multi-coil arrays were used to study the relationship between the spatial distribution of EFs and the structure of stimuli coils. By changing coil-driven strategies in a basic 16-coil array, we find that an EF induced by compactly distributed coils decays faster than that induced by dispersedly distributed coils, but the former has an advantage over the latter in terms of the activated brain volume. Simulation results also indicate that the attenuation rate of an EF induced by the 36-coil dense array is 3 times and 1.5 times greater than those induced by the 9-coil array and the 16-coil array, respectively. The EF evoked by the 36-coil dispense array has the slowest decay rate. This result demonstrates that larger multi-coil arrays, compared to smaller ones, activate deeper brain tissues at the expense of decreased focality. A further study on activating a specific field of a prescribed shape and size was conducted based on EF variation. Accurate target location was achieved with a 64-coil array 18 mm in diameter. A comparison between the figure-8 coil, the planar array, and the cap-formed array was made and demonstrates an improvement of multi-coil configurations in the penetration depth and the focality. These findings suggest

  15. Comprehensive Survey on Improved Focality and Penetration Depth of Transcranial Magnetic Stimulation Employing Multi-Coil Arrays.

    Science.gov (United States)

    Wei, Xile; Li, Yao; Lu, Meili; Wang, Jiang; Yi, Guosheng

    2017-11-14

    Multi-coil arrays applied in transcranial magnetic stimulation (TMS) are proposed to accurately stimulate brain tissues and modulate neural activities by an induced electric field (EF). Composed of numerous independently driven coils, a multi-coil array has alternative energizing strategies to evoke EFs targeting at different cerebral regions. To improve the locating resolution and the stimulating focality, we need to fully understand the variation properties of induced EFs and the quantitative control method of the spatial arrangement of activating coils, both of which unfortunately are still unclear. In this paper, a comprehensive analysis of EF properties was performed based on multi-coil arrays. Four types of planar multi-coil arrays were used to study the relationship between the spatial distribution of EFs and the structure of stimuli coils. By changing coil-driven strategies in a basic 16-coil array, we find that an EF induced by compactly distributed coils decays faster than that induced by dispersedly distributed coils, but the former has an advantage over the latter in terms of the activated brain volume. Simulation results also indicate that the attenuation rate of an EF induced by the 36-coil dense array is 3 times and 1.5 times greater than those induced by the 9-coil array and the 16-coil array, respectively. The EF evoked by the 36-coil dispense array has the slowest decay rate. This result demonstrates that larger multi-coil arrays, compared to smaller ones, activate deeper brain tissues at the expense of decreased focality. A further study on activating a specific field of a prescribed shape and size was conducted based on EF variation. Accurate target location was achieved with a 64-coil array 18 mm in diameter. A comparison between the figure-8 coil, the planar array, and the cap-formed array was made and demonstrates an improvement of multi-coil configurations in the penetration depth and the focality. These findings suggest that there is a

  16. Electrophysiological and pathological study of focal cortical dysplasia

    International Nuclear Information System (INIS)

    Hodozuka, Akira; Hashizume, Kiyotaka; Hayashi, Yoshimitsu; Tanaka, Tatsuya

    2008-01-01

    Clinical and experimental studies on focal cortical dysplasia (FCD) were carried out. For the experimental study, an experimental FCD model of rats was developed. Twenty Wistar rats at 0-2 days after birth were used for the study. Kainic acid (KA) solution was injected stereotaxically into medial and lateral sites of the sensori-motor cortex. Bipolar electrodes were inserted. The behavior of the rats and electroencephalography (EEG) were recorded using a digital video-EEG monitoring system. After observation periods of 1, 2 and 6 months, the rats were perfused for pathological study. FCD was observed adjacent to the site of KA injection in all rats more than one month after the injection. EEG recording demonstrated focal spike discharges in and around the site of injection. However, clinical seizure was not observed. Pathological studies showed decrease in gamma aminobutyric acid (GABA)-A receptors and increase in GABA-B receptors not only in the lesion but also in perilesional areas. Fifteen surgical cases of FCD with intractable epilepsy were included in the clinical study. Neuro-imaging studies including high-resolution MRI and single photon emission computed tomography (SPECT) were performed. Conventional EEG studies demonstrated focal EEG abnormalities with epileptic phenomena. At surgery, intraoperative electrocorticography (ECoG) was performed in order to localize epileptic foci under neuroleptanalgesia. Fourteen patients showed epileptiform discharges on preresection ECoG. All foci in non-eloquent areas were resected. Pathological studies including immunohistochemical staining were performed, and characteristics of the FCD in relation to EEG findings were analyzed. Electrophysiological examination revealed epileptogenecity not only in the lesions but also in perilesional areas. In the lesions, immunohistochemical studies showed decrease in GABA-A receptors and increase in GABA-B receptors in both the lesions and perilesional areas, but N

  17. Resveratrol and Estradiol Exert Disparate Effects on Cell Migration, Cell Surface Actin Structures, and Focal Adhesion Assembly in MDA-MB-231 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Nicolas G. Azios

    2005-02-01

    Full Text Available Resveratrol, a grape polyphenol, is thought to be a cancer preventive, yet its effects on metastatic breast cancer are relatively unknown. Since cancer cell invasion is dependent on cell migration, the chemotactic response of MDA-MB-231 metastatic human breast cancer cells to resveratrol, estradiol (E2, or epidermal growth factor (EGF was investigated. Resveratrol decreased while E2 and EGF increased directed cell migration. Resveratrol may inhibit cell migration by altering the cytoskeleton. Resveratrol induced a rapid global array of filopodia and decreased focal adhesions and focal adhesion kinase (FAK activity. E2 or EGF treatment did not affect filopodia extension but increased lamellipodia and associated focal adhesions that are integral for cell migration. Combined resveratrol and E2 treatment resulted in a filopodia and focal adhesion response similar to resveratrol alone. Combined resveratrol and EGF resulted in a lamellipodia and focal adhesion response similar to EGF alone. E2 and to a lesser extent resveratrol increased EGFR activity. The cytoskeletal changes and EGFR activity in response to E2 were blocked by EGFR1 inhibitor indicating that E2 may increase cell migration via crosstalk with EGFR signaling. These data suggest a promotional role for E2 in breast cancer cell migration but an antiestrogenic, preventative role for resveratrol.

  18. Pazopanib-Induced Hypertension in Patients With Renal Cell Carcinoma Is Associated With Low Urine Excretion of NO Metabolites

    DEFF Research Database (Denmark)

    Tinning, Anne Robdrup; Bengtsen, Camilla; Jensen, Niels Viggo

    2018-01-01

    -NAME or by impaired endothelin-1 leads to hypertension. The present study was designed to test the hypothesis that VEGF receptor inhibitor treatment leads to hypertension through decreased renal medullary formation of NO and endothelin-1. With a single-center prospective observational design, patients with metastatic...... increased, whereas heart rate decreased significantly; urine protein/creatinine ratio increased significantly, whereas estimated glomerular filtration rate was unchanged. Urine nitrite/nitrate (NOx) and cGMP/creatinine ratios decreased significantly, whereas urine endothelin-1/creatinine ratio and FENa...

  19. Focal epithelial hyperplasia arising after delivery of metal-ceramic fixed dental prosthesis.

    Science.gov (United States)

    Park, Min-Woo; Cho, Young-Ah; Kim, Soung-Min; Myoung, Hoon; Lee, Jong-Ho; Lee, Suk-Keun

    2014-12-01

    Focal epithelial hyperplasia (FEH) is a human papillomavirus (HPV)-induced alteration of the oral mucosa that presents with a clinically distinct appearance. While other HPV-infected lesions such as squamous papilloma, verruca vulgaris, and condyloma acuminatum involve the skin, oral mucosa, and genital mucosa, FEH occurs only in the oral mucosa. The affected oral mucosa exhibits multiple papules and nodules with each papule/nodule being flat-topped or sessile. The affected region resembles the normal color of oral mucosa rather than appearing as a white color since the epithelial surface is not hyperkeratinized. Almost all cases present with multiple sites of occurrence. This rare, benign epithelial proliferation is related to low-risk HPV, especially HPV-13 and -32, and is not transformed into carcinoma. We report a case of FEH that arose on the attached gingiva of an East Asian male adult related to prosthesis without detection of any HPV subtype in HPV DNA chip and sequencing.

  20. Cathodal Transcranial Direct Current Stimulation Improves Focal Hand Dystonia in Musicians: A Two-Case Study

    Directory of Open Access Journals (Sweden)

    Sara Marceglia

    2017-09-01

    Full Text Available Focal hand dystonia (FHD in musicians is a movement disorder causing abnormal movements and irregularities in playing. Since weak electrical currents applied to the brain induce persistent excitability changes in humans, cathodal tDCS was proposed as a possible non-invasive approach for modulating cortical excitability in patients with FHD. However, the optimal targets and modalities have still to be determined. In this pilot study, we delivered cathodal (2 mA, anodal (2 mA and sham tDCS over the motor areas bilaterally for 20 min daily for five consecutive days in two musicians with FHD. After cathodal tDCS, both patients reported a sensation of general wellness and improved symptoms of FHD. In conclusion, our pilot results suggest that cathodal tDCS delivered bilaterally over motor-premotor (M-PM cortex for 5 consecutive days may be effective in improving symptoms in FHD.

  1. Focal segmental glomerulosclerosis in a case of panhypopituitarism: a possible role of growth hormone treatment.

    Science.gov (United States)

    Fukasawa, H; Kato, A; Fujimoto, T; Suzuki, H; Fujigaki, Y; Yamamoto, T; Endoh, A; Yonemura, K; Hishida, A

    2002-10-01

    Panhypopituitarism manifests various symptoms including growth failure, hypothyroidism, adrenal insufficiency and hypogonadism. Dwarfism is an important problem in children with this condition, and long-term treatment with recombinant human growth hormone (GH) is usually required. We report a 24-year-old man with panhypopituitarism complicated by focal segmental glomerulosclerosis (FSGS). The patient had been treated with GH for hypopituitary dwarfism from 3 years of age. Proteinuria was initially noticed at 15 years of age and persisted despite cessation of GH supplementation at 18 years of age. A renal biopsy specimen showed glomerular hypertrophy and limited glomerulosclerosis, compatible with FSGS. To our knowledge, this is the first reported case of panhypopituitarism complicated by FSGS. Our case suggests that GH treatment for dwarfism may induce irreversible glomerular disease.

  2. Formation of multiple focal spots using a high NA lens with a complex spiral phase mask

    Science.gov (United States)

    Lalithambigai, K.; Anbarasan, P. M.; Rajesh, K. B.

    2014-07-01

    The formation of a transversally polarized beam by transmitting a tightly focused double-ring-shaped azimuthally polarized beam through a complex spiral phase mask and high numerical aperture lens is presented based on vector diffraction theory. The generation of transversally polarized focal spot segment splitting and multiple focal spots is illustrated numerically. Moreover, we found that a properly designed complex spiral phase mask can move the focal spots along the optical axis in the z direction. Therefore, one can achieve a focal segment of two, three or multiple completely transversely polarized focal spots, which finds applications in optical trapping and in material processing technologies.

  3. 'Focal thyroid inferno' on color Doppler ultrasonography: A specific feature of focal Hashimoto's thyroiditis

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Xianshui, E-mail: fuxs1968@163.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Guo, Limei, E-mail: guolimei@bjmu.edu.cn [Department of Pathology, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Zhang, Huabin, E-mail: huabinzhang@bjmu.edu.cn [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Ran, Weiqiang, E-mail: ranwq-sina@vip.sina.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Fu, Peng, E-mail: fupeng01@gmail.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Li, Zhiqiang, E-mail: lizhq126@126.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Chen, Wen, E-mail: wendy7989@sina.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Jiang, Ling, E-mail: papayaling@yahoo.com.cn [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Wang, Jinrui, E-mail: jinrui_wang@sina.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Jia, Jianwen, E-mail: drjia88@sohu.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China)

    2012-11-15

    Purpose: To evaluate color-Doppler features predictive of focal Hashimoto's thyroiditis. Materials and methods: A total of 521 patients with 561 thyroid nodules that underwent surgeries or gun biopsies were included in this study. These nodules were divided into three groups: focal Hashimoto's thyroiditis (104 nodules in 101 patients), benignity other than focal Hashimoto's thyroiditis (73 nodules in 70 patients), and malignancy (358 nodules in 350 patients). On color Doppler sonography, four vascularity types were determined as: hypovascularity, marked internal flow, marked peripheral flow and focal thyroid inferno. The {chi}{sup 2} test was performed to seek the potential vascularity type with the predictive ability of certain thyroid pathology. Furthermore, the gray-scale features of each nodule were also studied. Results: The vascularity type I (hypovascularity) was more often seen in focal Hashimoto's thyroiditis than other benignity and malignancy (46% vs. 20.5% and 19%). While the type II (marked internal flow) showed the opposite tendency (26.9% [focal Hashimoto's thyroiditis] vs. 45.2% [other benignity] and 52.8% [malignancy]). However, type III (marked peripheral flow) was unable to predict any thyroid pathology. Importantly, type IV (focal thyroid inferno) was exclusive to focal Hashimoto's thyroiditis. All 8 type IV nodules appeared to be solid, hypoechoic, and well-defined. Using 'focal thyroid inferno' as an indicator of FHT, the diagnostic sensitivity and specificity were 7.7% and 100% respectively. Conclusions: The vascularity type of 'focal thyroid inferno' is specific for focal Hashimoto thyroiditis. Recognition of this particular feature may avoid unnecessary interventional procedures for some solid hypoechoic thyroid nodules suspicious of malignancy.

  4. Sulforaphane exerts neuroprotective effects via suppression of the inflammatory response in a rat model of focal cerebral ischemia.

    Science.gov (United States)

    Ma, Li-Li; Xing, Guo-Ping; Yu, Yin; Liang, Hui; Yu, Tian-Xia; Zheng, Wei-Hong; Lai, Tian-Bao

    2015-01-01

    Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Sulforaphane exerts protective effects in a rat model of focal cerebral ischemia/reperfusion injury by alleviating brain edema. However, the possible mechanisms of sulforaphane after cerebral ischemia/reperfusion injury have not been fully elucidated. Therefore, in the present study, we investigated the effect of sulforaphane on inflammatory reaction and the potential molecular mechanisms in cerebral ischemia rats. We found that sulforaphane significantly attenuated the blood-brain barrier (BBB) disruption; decreased the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β; reduced the nitric oxide (NO) levels and inducible nitric oxide synthase (iNOS) activity; inhibited the expression of iNOS and cyclooxygenase-2 (COX-2). In addition, sulforaphane inhibits the expression of p-NF-κB p65 after focal cerebral ischemia-reperfusion injury. Taken together, our results suggest that sulforaphane suppresses the inflammatory response via inhibiting the NF-κB signaling pathway in a rat model of focal cerebral ischemia, and sulforaphane may be a potential therapeutic agent for the treatment of cerebral ischemia injury.

  5. Glucose-induced serum- and glucocorticoid-regulated kinase activation in oncofetal fibronectin expression

    International Nuclear Information System (INIS)

    Khan, Zia A.; Barbin, Yousef P.; Farhangkhoee, Hana; Beier, Norbert; Scholz, Wolfgang; Chakrabarti, Subrata

    2005-01-01

    Preferential expression of oncofetal extra domain-B fibronectin (EDB + FN), a proposed angiogenic marker, has been shown in proliferative diabetic retinopathy. High levels of glucose also increase EDB + FN expression in endothelial cells (ECs) via transforming growth factor-β1 (TGF-β1) and endothelin-1 (ET-1). The present study was aimed at elucidating the role of serum- and glucocorticoid-regulated kinase (SGK-1) in glucose-induced EDB + FN expression. Using human macro- and microvascular ECs, we show that high levels of glucose, TGF-β1, and ET-1 increase the EDB + FN expression via SGK-1 alteration at the mRNA, protein, and activity levels. Inhibition of TGF-β1 and ET-1 prevented glucose-induced SGK-1 activation and the EDB + FN expression. Furthermore, using siRNA-mediated SGK-1 gene silencing, we show that glucose-induced EDB + FN expression can be completely prevented. These findings provide first evidence of glucose-induced SGK-1 activation in altered EDB + FN expression and provide novel avenues for therapeutic modalities

  6. FOCAL EPILEPTIC MYOCLONUS IN KOZHEVNIKOV–RASMUSSEN SYNDROME

    Directory of Open Access Journals (Sweden)

    N. E. Kvaskova

    2016-01-01

    Full Text Available The article presents the clinical, electroencephalographic (EEG and neuroimaging features, as well as the results of treatment of patients with focal epileptic myoclonus (FEM with the Kozhevnikov–Rasmussen syndrome (KRS. FEM in KRS-patients was identified in 11 cases, accounting for 0.9 % of all the cases of epilepsy with the onset of seizures up to 18 years (n = 1261. The age at onset of KRS ranged from 3 to 21 years (average – 9.2 ± 5.7 years. In the active period of the disease of all patients in the clinical picture the active FEM appeared and increasing frequency of the secondary generalized seizures (SGS. In addition SGS and FEM, the clinical picture of the disease in most patients (91 % the focal motor (clonic and the somatosensory focal seizures were observed. As the disease progressed, the FEM became more pronounced in frequency and intensity, seized more muscle groups, localizing mainly in the muscles of the trunk and limbs. The typical EEG pattern of FEM patients with KRS was regional epileptiform activity that occurs in the structure of the continued regional slowing localizing maximum of the fronto-central-temporal region. During the magnetic resonance tomography of the brain in dynamics all the patients observed the increase in total cortical hemiatrophy. In all the cases, the appointment of antiepileptic therapy resulted in a slowing of the FEM, however, a complete remission was reached at none of the patients. Two patients were made surgical treatment of epilepsy. In one case remission of epileptic seizures was observed after right-side hemispherotomy. Our study showed that FEM is very resistant type of epileptic seizures. This fact calls for the identification of the FEM at the early stages of the disease with the purpose to improve the prognosis, as well as for an earlier surgical treatment.

  7. Temperament and character properties of primary focal hyperhidrosis patients

    Directory of Open Access Journals (Sweden)

    Ak Mehmet

    2013-01-01

    Full Text Available Abstract Background Primary focal hyperhidrosis is a health problem, which has negative effects on the patient's quality of life and significantly affects the patients’ daily activities, social and business life. The aim of this study is to evaluate temperament and character properties of patients diagnosed with primary focal hyperhidrosis. Methods Fifty-six primary focal hyperhidrosis (22.42 ± 7.80 and 49 control subjects (24.48 ± 5.17 participated in the study. Patients who met the diagnostic criteria for PFH were referred to psychiatry clinic where the subjects were evaluated through Structured Clinical Interview for DSM Disorders-I and Temperament and Character Inventory. Results In order to examine the difference between the PFH and control group in terms of temperament and character properties, one-way Multivariate Analysis of Variance (MANOVA was conducted. In terms of temperament properties, PFH group took significantly higher scores than control group in Fatigability and asthenia dimension. In terms of character properties, PFH group scored significantly lower than control group in Purposefulness , Resourcefulness , Self-Directedness and scored significantly higher than control group in Self-forgetfulness and Self-Transcendence. Conclusion Temperament and character features of PFH patients were different from healthy group and it was considered that these features were affected by many factors including genetic, biological, environmental, socio-cultural elements. During the follow-up of PFH cases, psychiatric evaluation is important and interventions, especially psychotherapeutic interventions can increase the chances of success of the dermatological treatments and can have a positive impact on the quality of life and social cohesion of chronic cases.

  8. Kalman Filter for Calibrating a Telescope Focal Plane

    Science.gov (United States)

    Kang, Bryan; Bayard, David

    2006-01-01

    The instrument-pointing frame (IPF) Kalman filter, and an algorithm that implements this filter, have been devised for calibrating the focal plane of a telescope. As used here, calibration signifies, more specifically, a combination of measurements and calculations directed toward ensuring accuracy in aiming the telescope and determining the locations of objects imaged in various arrays of photodetectors in instruments located on the focal plane. The IPF Kalman filter was originally intended for application to a spaceborne infrared astronomical telescope, but can also be applied to other spaceborne and ground-based telescopes. In the traditional approach to calibration of a telescope, (1) one team of experts concentrates on estimating parameters (e.g., pointing alignments and gyroscope drifts) that are classified as being of primarily an engineering nature, (2) another team of experts concentrates on estimating calibration parameters (e.g., plate scales and optical distortions) that are classified as being primarily of a scientific nature, and (3) the two teams repeatedly exchange data in an iterative process in which each team refines its estimates with the help of the data provided by the other team. This iterative process is inefficient and uneconomical because it is time-consuming and entails the maintenance of two survey teams and the development of computer programs specific to the requirements of each team. Moreover, theoretical analysis reveals that the engineering/ science iterative approach is not optimal in that it does not yield the best estimates of focal-plane parameters and, depending on the application, may not even enable convergence toward a set of estimates.

  9. Brivaracetam: a novel antiepileptic drug for focal-onset seizures.

    Science.gov (United States)

    Stephen, Linda J; Brodie, Martin J

    2018-01-01

    Brivaracetam (BRV), the n -propyl analogue of levetiracetam (LEV), is the latest antiepileptic drug (AED) to be licensed in Europe and the USA for the adjunctive treatment of focal-onset seizures with or without secondary generalization in patients aged 16 years or older. Like LEV, BRV binds to synaptic vesicle protein 2A (SV2A), but BRV has more selective binding and a 15- to 30-fold higher binding affinity than LEV. BRV is more effective than LEV in slowing synaptic vesicle mobilization and the two AEDs may act at different binding sites or interact with different conformational states of the SV2A protein. In animal models, BRV provides protection against focal and secondary generalized seizures and has significant anticonvulsant effects in genetic models of epilepsy. The drug undergoes first-order pharmacokinetics with an elimination half-life of 7-8 h. Although BRV is metabolized extensively, the main circulating compound is unchanged BRV. Around 95% of metabolites undergo renal elimination. No dose reduction is required in renal impairment, but it is recommended that the daily dose is reduced by one-third in hepatic dysfunction that may prolong half-life. BRV has a low potential for drug interactions. The efficacy and tolerability of adjunctive BRV in adults with focal-onset seizures have been explored in six randomized, placebo-controlled studies. These showed significant efficacy outcomes for doses of 50-200 mg/day. The most common adverse events reported were headache, somnolence, dizziness, fatigue and nausea. Patients who develop psychiatric symptoms with LEV appear to be at risk of similar side effects with BRV, although preliminary data suggest that these issues are likely to be less frequent and perhaps less severe. As with all AEDs, a low starting dose and slow titration schedule help to minimize side effects and optimize seizure control and thereby quality of life.

  10. Near infrared focal plane for the ISOCAM camera

    International Nuclear Information System (INIS)

    Epstein, G.; Stefanovitch, D.; Tiphene, D.; Carpentier, Y.; Lorans, D.

    1988-01-01

    ISOCAM is one of the science instruments in the Infrared Space Observatory. It is a 2-channel IR Astronomical Imager intended to observe at very low flux levels, thanks to the use of a liquid helium cooled telescope. This paper describes the Focal Plane Assembly design of the short wavelength channel. The operation of a 32 x 32 InSb CID-SAT array detector has been demonstrated. The problems encountered in the design of the cooled electronics and the component selection process are discussed in the light of specific ISO constraints, such as thermal control and radiation shielding. 6 references

  11. Difficulties in the interpretation of focal changes on liver scans

    Energy Technology Data Exchange (ETDEWEB)

    Derimanov, S.G. (Oblastnoj Onkologicheskij Dispanser, Veliko-Tyrnovo (Bulgaria))

    1983-01-01

    A series of cases are presented in which erroneous conclusions were arrived at by liver scans. The analysis of these errors has shown that they are determined by the similarity of a scanographic picture of focal changes in various diseases of the liver (cancer, cirrhosis, echinococcus, etc.) and the adjacent organs (bronchogenic cyst, renal tumor, etc.). In this connection all attempts to determine the etiology of a pathological process by liver scans without correlation with the results of multidimensional examination frequently result in errors.

  12. Focal dystonia in musicians: From phenomenology to therapy

    Directory of Open Access Journals (Sweden)

    Hans-Christian Jabusch

    2006-01-01

    Full Text Available Background: Musician's dystonia is a task-specific movement disorder which manifests itself as a loss of voluntary motor control in extensively trained movements. In many cases, the disorder terminates the careers of affected musicians. Approximately 1% of all professional musicians are affected.Etiology and Pathophysiology: The pathophysiology of the disorder is still unclear. Findings include (a reduced inhibition in different levels of the central nervous system, (b maladaptive plasticity, e.g. in the somatosensory cortex and in the basal ganglia, and (c alterations in sensorimotor processing. Epidemiological data demon-strated a higher risk for those musicians who play instruments requiring maximal fine-motorskills. For instruments where workload differs across hands, focal dystonia appears more often in the more intensely used hand. In psychological studies, musicians with dystonia had more perfectionist tendencies than healthy musicians. These findings streng then the assumption that behavioral factors may be involved in the etiology of musician's dystonia. Hereditary factors may play a greater role than previously assumed. Preliminary findings suggest a genetic contributiont o focal task-specific dystonia with phenotypic variations including musician's dystonia.Treatment: Treatment options for musician's dystonia include pharmacological interventions such as administration of Trihexyphenidyl or Botulinum Toxin-A as well as retraining programs and ergonomic changes in the instrument. A long-term follow-up study was performed in 144 patients with musician's dystonia. The outcome was revealed on average 8.4 years after onset of symptoms. Outcome was assessed by patients' subjective rating of cumulative treatmentresponse and response to individual therapies. Seventy-seven patients (54% reported an alleviation of symptoms: 33% of the patients with Trihexyphenidyl, 49% with Botulinum Toxin, 50% with pedagogical retraining, 56% with unmonitored

  13. Immunogenic hyperthyroidism following radioiodine ablation of focal autonomy

    International Nuclear Information System (INIS)

    Boddenberg, B.; Voth, E.; Schicha, H.

    1993-01-01

    Immunogenic hyperthyroidism rarely develops after radioiodine elimination of focal autonomous thyroid tissue. We observed this phenomenon in 8 patients between 1989 and 1992. The occurrence of immunogenic hyperthyroidism shortly after elimination of autonomous nodules has not been studied nor is it properly understood. Most studies known today describe the development of autonomous nodules in the course of immunogenic hyperthyroidism or ignore the chronologic order of occurrence. The possibility that immunogenic hyperthyroidism may occur after radioiodine therapy of autonomous nodules, makes a consequent follow-up within the first year following radioiodine therapy mandatory. (orig.) [de

  14. New focal plane detector system for the broad range spectrometer

    International Nuclear Information System (INIS)

    Sjoreen, T.P.

    1984-01-01

    A focal plane detector system consisting of a vertical drift chamber, parallel plate avalanche counters, and an ionization chamber with segmented anodes has been installed in the Broad Range Spectrometer at the Holifield Facility at Oak Ridge. The system, which has been designed for use with light-heavy ions with energies ranging from 10 to 25 MeV/amu, has a position resolution of approx. 0.1 mm, a scattering angle resolution of approx. 3 mrad, and a mass resolution of approx. 1/60

  15. Focal cemento-osseous dysplasia masquerading as a residual cyst.

    Science.gov (United States)

    Bhandari, Rajat; Sandhu, Simarpreet V; Bansal, Himanta; Behl, Rashi; Bhullar, Ramanpreet Kaur

    2012-04-01

    Focal cemento-osseous dysplasia (FCOD) is a benign fibroosseous condition that can be seen in dentulous and edentulous patients. It is an asymptomatic lesion and needs no treatment; however, follow-up is essential due to the possibility that it can progress to a condition called florid cemento-osseous dysplasia. We report a case of FCOD of mandible in a 25-year-old female. Clinically, the lesion resembled periapical pathosis of odontogenic origin. An attempt has been made to discuss the clinical and histopathologic features along with differential diagnosis of cemento-osseous dysplasia.

  16. Focal cemento-osseous dysplasia masquerading as a residual cyst

    Directory of Open Access Journals (Sweden)

    Rajat Bhandari

    2012-01-01

    Full Text Available Focal cemento-osseous dysplasia (FCOD is a benign fibroosseous condition that can be seen in dentulous and edentulous patients. It is an asymptomatic lesion and needs no treatment; however, follow-up is essential due to the possibility that it can progress to a condition called florid cemento-osseous dysplasia. We report a case of FCOD of mandible in a 25-year-old female. Clinically, the lesion resembled periapical pathosis of odontogenic origin. An attempt has been made to discuss the clinical and histopathologic features along with differential diagnosis of cemento-osseous dysplasia.

  17. Slow Activity in Focal Epilepsy During Sleep and Wakefulness

    DEFF Research Database (Denmark)

    Pellegrino, Giovanni; Tombini, Mario; Curcio, Giuseppe

    2017-01-01

    Introduction We aimed to test differences between healthy subjects and patients with respect to slow wave activity during wakefulness and sleep. Methods Fifteen patients affected by nonlesional focal epilepsy originating within temporal areas and fourteen matched controls underwent a 24-hour EEG....... The effect was widespread for alpha band and above, while localized over the affected hemisphere for delta (sleep cycle 1, P = .006; sleep cycle 2, P = .008; sleep cycle 3, P = .017). The analysis of interhemispheric differences showed that the only frequency band stronger over the affected regions...

  18. Caso severo de manifestaciones bucales de la hiperplasia epitelial focal

    OpenAIRE

    Jonathan Harris Ricardo; Natalia Fortich Mesa

    2012-01-01

    La hiperplasia epitelial focal, conocida también como enfermedad de Heck, es una patología benigna que se caracteriza por la presencia de múltiples pápulas en la mucosa de la cavidad bucal; es producida por los subtipos 13 y 32 del virus del papiloma humano, aunque también se le relaciona con factores genéticos, inmunosupresión e higiene bucal deficiente pero con poco sustento científico; afecta principalmente a niños y adolescentes. Se reporta caso clínico de paciente femenina de 7 años de e...

  19. Focal plane array with modular pixel array components for scalability

    Science.gov (United States)

    Kay, Randolph R; Campbell, David V; Shinde, Subhash L; Rienstra, Jeffrey L; Serkland, Darwin K; Holmes, Michael L

    2014-12-09

    A modular, scalable focal plane array is provided as an array of integrated circuit dice, wherein each die includes a given amount of modular pixel array circuitry. The array of dice effectively multiplies the amount of modular pixel array circuitry to produce a larger pixel array without increasing die size. Desired pixel pitch across the enlarged pixel array is preserved by forming die stacks with each pixel array circuitry die stacked on a separate die that contains the corresponding signal processing circuitry. Techniques for die stack interconnections and die stack placement are implemented to ensure that the desired pixel pitch is preserved across the enlarged pixel array.

  20. Subdural Empyema Presenting with Seizure, Confusion, and Focal Weakness

    Directory of Open Access Journals (Sweden)

    David I Bruner

    2012-12-01

    Full Text Available While sinusitis is a common ailment, intracranial suppurative complications of sinusitis are rare and difficult to diagnose and treat. The morbidity and mortality of intracranial complications of sinusitis have decreased significantly since the advent of antibiotics, but diseases such as subdural empyemas and intracranial abscesses still occur, and they require prompt diagnosis, treatment, and often surgical drainage to prevent death or long-term neurologic sequelae. We present a case of an immunocompetent adolescent male with a subdural empyema who presented with seizures,confusion, and focal arm weakness after a bout of sinusitis.