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Sample records for blockade induces long-term

  1. Long-term survival of intestinal allografts induced by costimulation blockade, busulfan and donor bone marrow infusion.

    Science.gov (United States)

    Guo, Zhong; Wang, Jun; Dong, Ying; Adams, Andrew B; Shirasugi, Nozomu; Kim, Oliver; Hart, John; Newton-West, Marvin; Pearson, Thomas C; Larsen, Christian P; Newell, Kenneth A

    2003-09-01

    Tolerance-inducing strategies that infuse donor bone marrow cells in conjunction with costimulation blockade have not been applied to intestinal transplantation. Intestines from BALB/c mice were transplanted into C57BL/6 recipients treated with anti-CD40L mAb, CTLA4-Ig, donor bone marrow, and busulfan. The majority of mice transplanted after completion of this regimen developed hematopoietic macrochimerism, although the degree of chimerism varied widely between recipients, and experienced long-term allograft survival. T cells from these mice demonstrated donor-specific hyporesponsiveness in vitro. However, T cells from chimeric mice proliferated to donor alloantigen in vivo. Furthermore, chimeric mice bearing intestinal allografts were capable of rejecting subsequently placed donor-strain skin grafts. These data suggest that although long-term allograft survival occurs in the absence of acute or chronic rejection, recipient mice are not completely unresponsive to donor alloantigens. When intestinal transplantation was performed at the time of initial bone marrow infusion (initiation of the chimerism protocol), most recipients failed to develop chimerism and promptly rejected the intestinal allograft. Although this is the most effective protocol that we have tested using this stringent model of transplantation, our observations suggest that modifications will be necessary before it can be reliably applied to the transplantation of highly immunogeneic organs like the intestine. PMID:12919088

  2. Long-term Benefit of PD-L1 Blockade in Lung Cancer Associated with JAK3 Activation.

    Science.gov (United States)

    Van Allen, Eliezer M; Golay, Hadrien G; Liu, Yan; Koyama, Shohei; Wong, Karrie; Taylor-Weiner, Amaro; Giannakis, Marios; Harden, Maegan; Rojas-Rudilla, Vanesa; Chevalier, Aaron; Thai, Tran; Lydon, Christine; Mach, Stacy; Avila, Ada G; Wong, Joshua A; Rabin, Alexandra R; Helmkamp, Joshua; Sholl, Lynette; Carter, Scott L; Oxnard, Geoffrey; Janne, Pasi; Getz, Gad; Lindeman, Neal; Hammerman, Peter S; Garraway, Levi A; Hodi, F Stephen; Rodig, Scott J; Dranoff, Glenn; Wong, Kwok-Kin; Barbie, David A

    2015-08-01

    PD-1 immune checkpoint blockade occasionally results in durable clinical responses in advanced metastatic cancers. However, mechanism-based predictors of response to this immunotherapy remain incompletely characterized. We performed comprehensive genomic profiling on a tumor and germline sample from a patient with refractory lung adenocarcinoma who achieved marked long-term clinical benefit from anti-PD-L1 therapy. We discovered activating somatic and germline amino acid variants in JAK3 that promoted PD-L1 induction in lung cancer cells and in the tumor immune microenvironment. These findings suggest that genomic alterations that deregulate cytokine receptor signal transduction could contribute to PD-L1 activation and engagement of the PD-1 immune checkpoint in lung cancer. PMID:26014096

  3. Anti-PD-1 Blockade and Stereotactic Radiation Produce Long-Term Survival in Mice With Intracranial Gliomas

    International Nuclear Information System (INIS)

    Purpose: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. Immunotherapy is a promising modality that could work synergistically with radiation, which has been shown to increase antigen presentation and promote a proinflammatory tumor microenvironment. Programmed-death-1 (PD-1) is a surface receptor expressed on activated and exhausted T cells, which mediate T cell inhibition upon binding with its ligand PD-L1, expressed on many tumor types including human GBMs. We tested the combination of anti-PD-1 immunotherapy with stereotactic radiosurgery in a mouse orthotopic GBM model. Methods and Materials: We performed intracranial implantation of mouse glioma cell line GL261 transfected with luciferase into C57BL/6 mice. Mice were stratified into 4 treatment groups: (1) control; (2) radiation only; (3) anti-PD-1 antibody only; and (4) radiation plus anti-PD-1 antibody. Overall survival was quantified. The mice were killed on day 21 after implantation to assess immunologic parameters in the brain/tumor, cervical lymph nodes, and spleen. Results: Improved survival was demonstrated with combination anti-PD-1 therapy plus radiation compared with either modality alone: median survival was 25 days in the control arm, 27 days in the anti-PD-1 antibody arm, 28 days in the radiation arm, and 53 days in the radiation plus anti-PD-1 therapy arm (P<.05 by log-rank Mantle-Cox). Long-term survival was seen only in the combined treatment arm, with a fraction (15%-40%) of animals alive at day 180+ after treatment. Immunologic data on day 21 after implantation showed increased tumor infiltration by cytotoxic T cells (CD8+/interferon-γ+/tumor necrosis factor-α+) and decreased regulatory T cells (CD4+/FOXP3) in the combined treatment group compared with the single modality arms. Conclusions: The combination of PD-1 blockade and localized

  4. Anti-PD-1 Blockade and Stereotactic Radiation Produce Long-Term Survival in Mice With Intracranial Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Jing [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); See, Alfred P.; Phallen, Jillian; Jackson, Christopher M.; Belcaid, Zineb; Ruzevick, Jacob [Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Durham, Nicholas [Department of Immunology, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Meyer, Christian [Department of Oncology, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Harris, Timothy J. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Albesiano, Emilia; Pradilla, Gustavo [Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Ford, Eric; Wong, John [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Hammers, Hans-Joerg [Department of Immunology, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Mathios, Dimitris; Tyler, Betty; Brem, Henry [Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Tran, Phuoc T. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Pardoll, Drew; Drake, Charles G. [Department of Immunology, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); and others

    2013-06-01

    Purpose: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. Immunotherapy is a promising modality that could work synergistically with radiation, which has been shown to increase antigen presentation and promote a proinflammatory tumor microenvironment. Programmed-death-1 (PD-1) is a surface receptor expressed on activated and exhausted T cells, which mediate T cell inhibition upon binding with its ligand PD-L1, expressed on many tumor types including human GBMs. We tested the combination of anti-PD-1 immunotherapy with stereotactic radiosurgery in a mouse orthotopic GBM model. Methods and Materials: We performed intracranial implantation of mouse glioma cell line GL261 transfected with luciferase into C57BL/6 mice. Mice were stratified into 4 treatment groups: (1) control; (2) radiation only; (3) anti-PD-1 antibody only; and (4) radiation plus anti-PD-1 antibody. Overall survival was quantified. The mice were killed on day 21 after implantation to assess immunologic parameters in the brain/tumor, cervical lymph nodes, and spleen. Results: Improved survival was demonstrated with combination anti-PD-1 therapy plus radiation compared with either modality alone: median survival was 25 days in the control arm, 27 days in the anti-PD-1 antibody arm, 28 days in the radiation arm, and 53 days in the radiation plus anti-PD-1 therapy arm (P<.05 by log-rank Mantle-Cox). Long-term survival was seen only in the combined treatment arm, with a fraction (15%-40%) of animals alive at day 180+ after treatment. Immunologic data on day 21 after implantation showed increased tumor infiltration by cytotoxic T cells (CD8+/interferon-γ+/tumor necrosis factor-α+) and decreased regulatory T cells (CD4+/FOXP3) in the combined treatment group compared with the single modality arms. Conclusions: The combination of PD-1 blockade and localized

  5. Effect of ganglionic blockade on endogenous circulating pancreatic polypeptide, vasoactive intestinal polypeptide, substance P, neurotensin and noradrenaline in healthy controls and long-term insulin-dependent diabetic patients

    DEFF Research Database (Denmark)

    Kastrup, J; Henriksen, Jens Henrik Sahl; Pedersen, J H; Fahrenkrug, J; Schaffalitzky de Muckadell, O B; Schwartz, T; Parving, H H; Christensen, N J

    1986-01-01

    infusion of the ganglionic blocking agent trimethaphan camsylate, in order to determine the influence of the autonomic nervous system on the baseline values of the substances. The basal levels of the measured substances were not significantly different in healthy subjects and patients with or without...... diabetic autonomic neuropathy. In healthy subjects, the ganglionic blockade induced a significant decrease in PP (80%) (P less than 0.02), NA (58%) (P less than 0.05), NT (27%) (P less than 0.05) and a significant increase in SP (30%) (P less than 0.05), while the VIP concentration remained unchanged. The...... substances during ganglionic blockade. The results indicate that the postganglionic part of the autonomic nervous system participates in the maintenance of a normal baseline level of PP, NT and NA, but not of VIP. The regulation of VIP may be disturbed in long-term diabetic subjects....

  6. Long-term Opioid Blockade and Hedonic Response: Preliminary Data from Two Open-Label Extension Studies with Extended-Release Naltrexone

    OpenAIRE

    O’Brien, Charles P.; Gastfriend, David R.; Forman, Robert F.; Schweizer, Edward; Pettinati, Helen M.

    2010-01-01

    The emergence of extended-release naltrexone (XR-NTX) raises the opportunity to explore the role of endorphin blockade on hedonic response during long-term alcohol dependence treatment. A hedonic survey was administered to 74 alcohol dependent patients treated for an average of 3.5 years with nearly continuous month-long intramuscular XR-NTX. The paper-and-pencil, one-time survey asked patients about the degree of pleasure they experience in the past 90 days with drinking alcohol, sex, exerci...

  7. Foraminiferal survival after long term experimentally induced anoxia

    Directory of Open Access Journals (Sweden)

    D. Langlet

    2013-06-01

    Full Text Available Anoxia has been successfully induced in four benthic chambers installed on the Northern Adriatic seafloor from 1 week to 10 months. To accurately determine whether benthic foraminifera can survive experimentally induced prolonged anoxia, the CellTrackerGreen method has been applied. Numerous individuals have been found living at all sampling times and at all sampling depths, showing that benthic foraminifera can survive up to 10 months of anoxia with co-occurring hydrogen sulphides. However, foraminiferal standing stocks decrease with sampling time in an irregular way. A large difference in standing stock between two cores samples in initial conditions indicates the presence of a large spatial heterogeneity of the foraminiferal faunas. An unexpected increase in standing stocks after 1 month is tentatively interpreted as a reaction to increased food availability due to the massive mortality of infaunal macrofaunal organisms. After this, standing stocks decrease again in a core sampled after 2 months of anoxia, to attain a minimum in the cores sampled after 10 months. We speculate that the trend of overall decrease of standing stocks is not due to the adverse effects of anoxia and hydrogen sulphides, but rather due to a continuous diminution of labile organic matter.

  8. Losartan prevents heart fibrosis induced by long-term intensive exercise in an animal model

    OpenAIRE

    Gemma Gay-Jordi; Eduard Guash; Begoña Benito; Josep Brugada; Stanley Nattel; Lluís Mont; Anna Serrano-Mollar

    2013-01-01

    Rationale: Recently it has been shown that long-term intensive exercise practice is able to induce myocardial fibrosis in an animal model. Angiotensin II is a profibrotic hormone that could be involved in the cardiac remodeling resulting from endurance exercise. Objective: This study examined the antifibrotic effect of losartan, an angiotensin II type 1 receptor antagonist, in an animal model of heart fibrosis induced by long-term intense exercise. Methods and Results: Male Wistar rats were r...

  9. Long-Term Exposure to High Corticosterone Levels Inducing a Decrease of Adenylate Kinase 1 Activity

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yu'nan; SHEN Jia; SU Hui; HUANG Yufang; XING Dongming; DU Lijun

    2009-01-01

    Corticosterone, a principal glucocorticoid synthesized in the rodent adrenal cortex, can be cumula-tively toxic to hippocampal neurons, the cause of which is not known. The present study determined whether the cytosol adenylate kinase (AK) system was involved in the neuronal damage induced by long-term exposure to high corticosterone levels. We investigated the effects of long-term exposure to high corticosterone levels on AK1 activity, AK1 mRNA expression, and energy levels in cultured hippocampal neurons. The results show that long-term exposure to high corticosterone levels induces a reduction of the cultured hippocampal neuron viability, significantly reduces energy levels, and causes a time-dependant re-duction of the AK1 activity. These findings indicate that changes in the AK system might be the mechanism underlying neuronal damage induced by long-term exposure to high corticosterone levels.

  10. The shear-induced alpha-effect and long-term variations in solar dynamo

    OpenAIRE

    Pipin, V. V.

    2007-01-01

    The consequences of the shear-induced alpha effect to the long-term modulation of magnetic activity are examined with the help of the axisymmetric numerical dynamo model that includes the self-consistent description of the angular momentum balance, heat transport and magnetic field generation in the spherical shell. We find that the shear contributions to alpha effect can complicate the long-term behaviour of the large-scale magnetic activity and differential rotation in nonlinear dynamo. Add...

  11. Hippocampal Place Cell Firing Patterns can Induce Long-Term Synaptic Plasticity In Vitro

    OpenAIRE

    Isaac, John T. R.; Buchanan, Katherine A.; Muller, Robert U.; Mellor, Jack R.

    2009-01-01

    In the hippocampus, synaptic strength between pyramidal cells is modifiable by NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) and long-term depression (LTD), both of which require coincident pre- and postsynaptic activity. In vivo, many pyramidal cells exhibit location-specific activity patterns and are known as “place cells”. The combination of these factors suggests that synaptic plasticity will be induced at synapses connecting place cells with overlapping firing fields, sinc...

  12. Long-term opioid blockade and hedonic response: preliminary data from two open-label extension studies with extended-release naltrexone.

    Science.gov (United States)

    O'Brien, Charles P; Gastfriend, David R; Forman, Robert F; Schweizer, Edward; Pettinati, Helen M

    2011-01-01

    The emergence of extended-release naltrexone (XR-NTX) raises the opportunity to explore the role of endorphin blockade on hedonic response during long-term alcohol dependence treatment. A hedonic survey was administered to 74 alcohol dependent patients treated for an average of 3.5 years with nearly continuous month-long intramuscular XR-NTX. The paper-and-pencil, one-time survey asked patients about the degree of pleasure they experienced in the past 90 days with drinking alcohol, sex, exercise and other daily activities. The data revealed lower pleasure ratings for alcohol than for sex, exercise and 10 other common activities. Mean responses to drinking alcohol and gambling were significantly lower than to listening to music, sex, reading, being with friends, eating good food, eating spicy food, and playing video/card games. This effect was independent of XR-NTX dose or duration. Although this exploratory study lacked baseline data, a comparison group or control for the impact of patient discontinuation, the data indicate the feasibility of examining long-term hedonic response in recovery. The differential hedonic ratings suggest that, in patients who persist with long-term continuous therapy, XR-NTX may selectively inhibit the pleasure associated with drinking alcohol, compared to a variety of other activities.  PMID:21314752

  13. Studies on radiation induced radicals in irradiated black pepper after long-term storage

    International Nuclear Information System (INIS)

    Using ESR the radiation induced radicals of black pepper after long-term storage were studied. Upon gamma ray irradiation, new signals were detected as twin peaks. It was revealed that these signals were very stable after the six month storage. We concluded that radiation induced new signals are very useful to know that the black pepper was irradiated or not. (author)

  14. Presynaptic protein synthesis required for NT-3-induced long-term synaptic modulation

    Directory of Open Access Journals (Sweden)

    Je H

    2011-01-01

    Full Text Available Abstract Background Neurotrophins elicit both acute and long-term modulation of synaptic transmission and plasticity. Previously, we demonstrated that the long-term synaptic modulation requires the endocytosis of neurotrophin-receptor complex, the activation of PI3K and Akt, and mTOR mediated protein synthesis. However, it is unclear whether the long-term synaptic modulation by neurotrophins depends on protein synthesis in pre- or post-synaptic cells. Results Here we have developed an inducible protein translation blocker, in which the kinase domain of protein kinase R (PKR is fused with bacterial gyrase B domain (GyrB-PKR, which could be dimerized upon treatment with a cell permeable drug, coumermycin. By genetically targeting GyrB-PKR to specific cell types, we show that NT-3 induced long-term synaptic modulation requires presynaptic, but not postsynaptic protein synthesis. Conclusions Our results provide mechanistic insights into the cell-specific requirement for protein synthesis in the long-term synaptic modulation by neurotrophins. The GyrB-PKR system may be useful tool to study protein synthesis in a cell-specific manner.

  15. Marked Recovery From Paraquat-Induced Lung Injury During Long-Term Follow-up

    OpenAIRE

    Lee, Kwon-Hyun; Gil, Hyo-Wook; Kim, Young-Tong; Yang, Jong-Oh; Lee, Eun-Young; Hong, Sae-Yong

    2009-01-01

    Background/Aims Paraquat-induced lung injury has been considered a progressive and irreversible disease. The purpose of this study was to report the long-term evolution of lung lesions in eight survivors with significant paraquat-induced lung injuries who could be followed-up for longer than 6 months. Methods We retrospectively examined high-resolution computed tomography and pulmonary function test of eight survivors with significant paraquat-induced lung injurys. Results High-resolution com...

  16. Long-term prognosis for transplant-free survivors of paracetamol-induced acute liver failure

    OpenAIRE

    Jepsen, Peter; Schmidt, Lars E; Larsen, Fin Stolze; Vilstrup, Hendrik

    2010-01-01

    Abstract Background: The prognosis for transplant-free survivors of paracetamol-induced acute liver failure is unknown. Aim: To examine whether paracetamol-induced acute liver failure increases long-term mortality. Methods: We followed all transplant-free survivors of paracetamol-induced acute liver injury hospitalized in a Danish national referral center during 1984-2004. We compared age-specific mortality rates from one year post-discharge through 2008 between those in wh...

  17. Profound thrombocytopenia induced by clopidogrel with a prior history of long-term safe administration

    OpenAIRE

    Guo, Yuan-Lin; Li, Jian-Jun; Yuan, Jin-qing; Qin, Xue-Wen; Zheng, Xin; Mu, Chao-Wei; Hua, Yi-Hong

    2010-01-01

    Clopidogrel has shown an excellent safety, tolerability and efficacy ever since its marketing. However, here we report a rare case with profound thrombocytopenia following clopidogrel administration previously safely exposed to this same drug. This reminds us that thrombocytopenia might be induced by clopidogrel even with a prior, safe history of long-term administration.

  18. Low-frequency stimulation induces long-term depression and slow onset long-term potentiation at perforant path-dentate gyrus synapses in vivo

    OpenAIRE

    Gonzalez, Jossina; Isaiah S Morales; Villarreal, Desiree M.; Derrick, Brian E.

    2013-01-01

    The expression of homosynaptic long-term depression (LTD) is thought to mediate a crucial role in sustaining memory function. Our in vivo investigations of LTD expression at lateral (LPP) and medial perforant path (MPP) synapses in the dentate gyrus (DG) corroborate prior demonstrations that PP-DG LTD is difficult to induce in intact animals. In freely moving animals, LTD expression occurred inconsistently among LPP-DG and MPP-DG responses. Interestingly, following acute electrode implantatio...

  19. Long-term voluntary running improves diet-induced adiposity in young adult mice

    Science.gov (United States)

    The present study investigated the effects of long-term voluntary running on diet-induced adiposity in male C57BL/6 mice. Four-week old mice (n = 15 per group) were fed the AIN93G diet or a 45% high-fat diet (% kcal.) with or without access to in-cage activity wheels for 14 weeks. The high-fat die...

  20. Enhanced acoustic cavitation following laser-induced bubble formation : long-term memory effect

    OpenAIRE

    Yavaṣ, Oğuz; Leiderer, Paul; Park, Hee K.; Grigoropoulos, Costas P.; Poon, Chie C.; Tam, Andrew C.

    1994-01-01

    The enhancement of acoustic caviation at a liquid-solid interface following laser-induced bubble formation is studied. The experiment results indicate that metastable ultramicroscopic bubbles formed on the solid surface cause a long-term memory effect on acoustic cavitation. By performing a double-pulse experiment using two excimer lasers, the temporal decay of this memory effect is determined for two different liquids on a chromium surface. An explanation of the observed decay mode by a ...

  1. Dopaminergic neurotransmission dysfunction induced by amyloid-β transforms cortical long-term potentiation into long-term depression and produces memory impairment.

    Science.gov (United States)

    Moreno-Castilla, Perla; Rodriguez-Duran, Luis F; Guzman-Ramos, Kioko; Barcenas-Femat, Alejandro; Escobar, Martha L; Bermudez-Rattoni, Federico

    2016-05-01

    Alzheimer's disease (AD) is a neurodegenerative condition manifested by synaptic dysfunction and memory loss, but the mechanisms underlying synaptic failure are not entirely understood. Although dopamine is a key modulator of synaptic plasticity, dopaminergic neurotransmission dysfunction in AD has mostly been associated to noncognitive symptoms. Thus, we aimed to study the relationship between dopaminergic neurotransmission and synaptic plasticity in AD models. We used a transgenic model of AD (triple-transgenic mouse model of AD) and the administration of exogenous amyloid-β (Aβ) oligomers into wild type mice. We found that Aβ decreased cortical dopamine levels and converted in vivo long-term potentiation (LTP) into long-term depression (LTD) after high-frequency stimulation delivered at basolateral amygdaloid nucleus-insular cortex projection, which led to impaired recognition memory. Remarkably, increasing cortical dopamine and norepinephrine levels rescued both high-frequency stimulation -induced LTP and memory, whereas depletion of catecholaminergic levels mimicked the Aβ-induced shift from LTP to LTD. Our results suggest that Aβ-induced dopamine depletion is a core mechanism underlying the early synaptopathy and memory alterations observed in AD models and acts by modifying the threshold for the induction of cortical LTP and/or LTD. PMID:27103531

  2. Prevention by the cannabinoid antagonist, SR141716A, of cannabinoid-mediated blockade of long-term potentiation in the rat hippocampal slice.

    OpenAIRE

    D. R. Collins; Pertwee, R. G.; Davies, S. N.

    1995-01-01

    Incubation of rat hippocampal slices in the presence of the synthetic cannabinoid (-)-11-OH-delta 8-dimethylheptyl tetrahydrocannabinol (HU-210) (100 nM) prevented the induction of long-term potentiation (LTP). Slices co-incubated with both HU-210 (100 nM) and the cannabinoid antagonist, SR141716A (100 nM), exhibited tetanically induced LTP, comparable to control slices. Intriguingly, coincubation with HU-210 and SR141716A prevented the induction of the early, short-term phase of LTP.

  3. Losartan prevents heart fibrosis induced by long-term intensive exercise in an animal model.

    Directory of Open Access Journals (Sweden)

    Gemma Gay-Jordi

    Full Text Available RATIONALE: Recently it has been shown that long-term intensive exercise practice is able to induce myocardial fibrosis in an animal model. Angiotensin II is a profibrotic hormone that could be involved in the cardiac remodeling resulting from endurance exercise. OBJECTIVE: This study examined the antifibrotic effect of losartan, an angiotensin II type 1 receptor antagonist, in an animal model of heart fibrosis induced by long-term intense exercise. METHODS AND RESULTS: Male Wistar rats were randomly distributed into 4 experimental groups: Exercise, Exercise plus losartan, Sedentary and Sedentary plus losartan. Exercise groups were conditioned to run vigorously for 16 weeks. Losartan was orally administered daily before each training session (50 mg/kg/day. Time-matched sedentary rats served as controls. After euthanasia, heart hypertrophy was evaluated by histological studies; ventricular collagen deposition was quantified by histological and biochemical studies; and messenger RNA and protein expression of transforming growth factor-β1, fibronectin-1, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, procollagen-I and procollagen-III was evaluated in all 4 cardiac chambers. Daily intensive exercise caused hypertrophy in the left ventricular heart wall and originated collagen deposition in the right ventricle. Additionally long-term intensive exercise induced a significant increase in messenger RNA expression and protein synthesis of the major fibrotic markers in both atria and in the right ventricle. Losartan treatment was able to reduce all increases in messenger RNA expression and protein levels caused by exercise, although it could not completely reverse the heart hypertrophy. CONCLUSIONS: Losartan treatment prevents the heart fibrosis induced by endurance exercise in training animals.

  4. Long term highly saturated fat diet does not induce NASH in Wistar rats

    OpenAIRE

    Romestaing, Caroline; Piquet, Marie-Astrid; Bedu, Elodie; Rouleau, Vincent; Dautresme, Marianne; Hourmand-Ollivier, Isabelle; Filippi, Céline; Duchamp, Claude; Sibille, Brigitte

    2007-01-01

    Background Understanding of nonalcoholic steatohepatitis (NASH) is hampered by the lack of a suitable model. Our aim was to investigate whether long term high saturated-fat feeding would induce NASH in rats. Methods 21 day-old rats fed high fat diets for 14 weeks, with either coconut oil or butter, and were compared with rats feeding a standard diet or a methionine choline-deficient (MCD) diet, a non physiological model of NASH. Results MCDD fed rats rapidly lost weight and showed NASH featur...

  5. Long term highly saturated fat diet does not induce NASH in Wistar rats

    OpenAIRE

    Romestaing, C.; PIQUET, MA; Bedu, E.; Rouleau, V.; Dautresme, M.; Hourmand-Ollivier, I.; Filippi, C.; Duchamp, C.; Sibille, B.

    2007-01-01

    Background: Understanding of nonalcoholic steatohepatitis (NASH) is hampered by the lack of a suitable model. Our aim was to investigate whether long term high saturated-fat feeding would induce NASH in rats. Methods: 21 day-old rats fed high fat diets for 14 weeks, with either coconut oil or butter, and were compared with rats feeding a standard diet or a methionine choline-deficient (MCD) diet, a non physiological model of NASH. Results: MCDD fed rats rapidly lost weight and showed NASH fea...

  6. Long term highly saturated fat diet does not induce NASH in Wistar rats

    OpenAIRE

    Filippi Céline; Duchamp Claude; Hourmand-Ollivier Isabelle; Dautresme Marianne; Rouleau Vincent; Bedu Elodie; Piquet Marie-Astrid; Romestaing Caroline; Sibille Brigitte

    2007-01-01

    Abstract Background Understanding of nonalcoholic steatohepatitis (NASH) is hampered by the lack of a suitable model. Our aim was to investigate whether long term high saturated-fat feeding would induce NASH in rats. Methods 21 day-old rats fed high fat diets for 14 weeks, with either coconut oil or butter, and were compared with rats feeding a standard diet or a methionine choline-deficient (MCD) diet, a non physiological model of NASH. Results MCDD fed rats rapidly lost weight and showed NA...

  7. Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response.

    Science.gov (United States)

    Woo, Sun-Je; Kang, Seok-Seong; Park, Sung-Moo; Yang, Jae Seung; Song, Man Ki; Yun, Cheol-Heui; Han, Seung Hyun

    2015-10-01

    Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4(+) T cells in the lung. PA-specific CD4(+) T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity. PMID:26278659

  8. Binge-pattern alcohol exposure during puberty induces long-term changes in HPA axis reactivity.

    Directory of Open Access Journals (Sweden)

    Magdalena M Przybycien-Szymanska

    Full Text Available Adolescence is a dynamic and important period of brain development however, little is known about the long-term neurobiological consequences of alcohol consumption during puberty. Our previous studies showed that binge-pattern ethanol (EtOH treatment during pubertal development negatively dysregulated the responsiveness of the hypothalamo-pituitary-adrenal (HPA axis, as manifested by alterations in corticotrophin-releasing hormone (CRH, arginine vasopressin (AVP, and corticosterone (CORT during this time period. Thus, the primary goal of this study was to determine whether these observed changes in important central regulators of the stress response were permanent or transient. In this study, juvenile male Wistar rats were treated with a binge-pattern EtOH treatment paradigm or saline alone for 8 days. The animals were left undisturbed until adulthood when they received a second round of treatments consisting of saline alone, a single dose of EtOH, or a second binge-pattern treatment paradigm. The results showed that pubertal binge-pattern EtOH exposure induced striking long-lasting alterations of many HPA axis parameters. Overall, our data provide strong evidence that binge-pattern EtOH exposure during pubertal maturation has long-term detrimental effects for the healthy development of the HPA axis.

  9. Endocannabinoid Modulation of Predator Stress-Induced Long-Term Anxiety in Rats.

    Science.gov (United States)

    Lim, James; Igarashi, Miki; Jung, Kwang-Mook; Butini, Stefania; Campiani, Giuseppe; Piomelli, Daniele

    2016-04-01

    Individuals who experience life-threatening psychological trauma are at risk of developing a series of chronic neuropsychiatric pathologies that include generalized anxiety, depression, and drug addiction. The endocannabinoid system has been implicated in the modulation of these responses by regulating the activity of the amygdala and the hypothalamic-pituitary-adrenal axis. However, the relevance of this signaling complex to the long-term consequences of traumatic events is unclear. Here we use an animal model of predatory stress-induced anxiety-like behavior to investigate the role of the endocannabinoid system in the development of persistent anxiety states. Our main finding is that rats exposed to the fox pheromone 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a life-threatening stimulus for rodents, display a marked and selective increase in the mobilization of the endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG), in the amygdala. This effect lasts for at least 14 days after the stress has occurred. In addition, systemic or local pharmacological inhibition of monoacylglycerol lipase (MGL)-a lipid hydrolase that degrades 2-AG in presynaptic nerve terminals-elevates 2-AG levels and suppresses the anxiety-like behavior elicited by exposure to TMT. The results suggest that predator threat triggers long-term changes in 2-AG-mediated endocannabinoid signaling in the amygdala, and that pharmacological interventions targeting MGL might provide a therapeutic strategy for the treatment of chronic brain disorders initiated by trauma. PMID:26361059

  10. Long-term intensive training induced brain structural changes in world class gymnasts.

    Science.gov (United States)

    Huang, Ruiwang; Lu, Min; Song, Zheng; Wang, Jun

    2015-03-01

    Many previous studies suggested that both short-term and long-term motor training can modulate brain structures. However, little evidence exists for such brain anatomical changes in top-level gymnasts. Using diffusion-weighted and structural magnetic resonance images of the human brain, we applied voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) as well as FA-VBA (voxel-based analysis of fractional anisotropy, a VBM-style analysis) methods to quantitatively compare the brain structural differences between the world class gymnasts (WCG) and the non-athlete groups. In order to reduce the rate of false positive findings, we first determined that the clusters defined at a threshold of t > 2.3 and a cluster significance of p gymnasts' extraordinary ability to estimate the direction of their movements, their speed of execution, and their identification of their own and surrounding objects' locations. Our findings suggest that our method of constructing intersecting regions from multiple between-group comparison can considerably reduce the false positives, and our results provide new insights into the brain structure changes induced by long-term intensive gymnastic training. PMID:24297657

  11. Parental knowledge reduces long term anxiety induced by false-positive test results after newborn screening for cystic fibrosis

    Directory of Open Access Journals (Sweden)

    A.M.M. Vernooij-van Langen

    2014-01-01

    Conclusions: A positive screening test result induces parental anxiety but false positive test results in NBSCF do not seem to cause long-term anxiety. Well-informed parents show lower stress and anxiety levels.

  12. Changes in presynaptic release, but not reuptake, of bioamines induced by long-term antidepressant treatment

    International Nuclear Information System (INIS)

    This paper describes an investigation into the effect of long-term administration of antidepressants on neuronal uptake of NA and 5-HT and on their release, induced by electrical stimulation, in rat brain slices. The effects of the test substances on neuronal uptake of 14C-NA and 3H-5-HT by the slices was investigated. Values of IC50 and EC2 were found and compared in the experiments and control. The inhibitory effect of clonidine (10-4 M) and of 5-HT (10-5 M) on presynaptic release of 14C-NA and 3H-5-HT also was studied in brain slices from intact rats and rats treated for two weeks with antidepressants

  13. Long-term drift induced by the electronic crosstalk in Terra MODIS Band 29

    Science.gov (United States)

    Sun, Junqiang; Madhavan, Sriharsha; Xiong, Xiaoxiong; Wang, Menghua

    2015-10-01

    Terra MODerate Resolution Imaging Spectroradiometer (MODIS) is one of the key sensors in the NASA's Earth Observing System, which has successfully completed 15 years of on-orbit operation. Terra MODIS continues to collect valuable information of the Earth's energy radiation from visible to thermal infrared wavelengths. The instrument has been well characterized over its lifetime using onboard calibrators whose calibration references are traceable to the National Institute of Standards and Technology standards. In this paper, we focus on the electronic crosstalk effect of Terra MODIS band 29, a thermal emissive band (TEB) whose center wavelength is 8.55 µm. Previous works have established the mechanism to describe the effect of the electronic crosstalk in the TEB channels of Terra MODIS. This work utilizes the established methodology to apply to band 29. The electronic crosstalk is identified and characterized using the regularly scheduled lunar observations. The moon being a near-pulse-like source allowed easy detection of extraneous signals around the actual Moon surface. First, the crosstalk-transmitting bands are identified along with their amplitudes. The crosstalk effect then is characterized using a moving average mechanism that allows a high fidelity of the magnitude to be corrected. The lunar-based analysis unambiguously shows that the crosstalk contamination is becoming more severe in recent years and should be corrected in order to maintain calibration quality for the affected spectral bands. Finally, two radiometrically well-characterized sites, Pacific Ocean and Libya 1 desert, are used to assess the impact of crosstalk effect. It is shown that the crosstalk contamination induces a long-term upward drift of 1.5 K in band 29 brightness temperature of MODIS Collection 6 L1B, which could significantly impact the science products. The crosstalk effect also induces strong detector-to-detector differences, which result in severe stripping in the Earth view

  14. Long term highly saturated fat diet does not induce NASH in Wistar rats

    Directory of Open Access Journals (Sweden)

    Filippi Céline

    2007-02-01

    Full Text Available Abstract Background Understanding of nonalcoholic steatohepatitis (NASH is hampered by the lack of a suitable model. Our aim was to investigate whether long term high saturated-fat feeding would induce NASH in rats. Methods 21 day-old rats fed high fat diets for 14 weeks, with either coconut oil or butter, and were compared with rats feeding a standard diet or a methionine choline-deficient (MCD diet, a non physiological model of NASH. Results MCDD fed rats rapidly lost weight and showed NASH features. Rats fed coconut (86% of saturated fatty acid or butter (51% of saturated fatty acid had an increased caloric intake (+143% and +30%. At the end of the study period, total lipid ingestion in term of percentage of energy intake was higher in both coconut (45% and butter (42% groups than in the standard (7% diet group. No change in body mass was observed as compared with standard rats at the end of the experiment. However, high fat fed rats were fattier with enlarged white and brown adipose tissue (BAT depots, but they showed no liver steatosis and no difference in triglyceride content in hepatocytes, as compared with standard rats. Absence of hepatic lipid accumulation with high fat diets was not related to a higher lipid oxidation by isolated hepatocytes (unchanged ketogenesis and oxygen consumption or hepatic mitochondrial respiration but was rather associated with a rise in BAT uncoupling protein UCP1 (+25–28% vs standard. Conclusion Long term high saturated fat feeding led to increased "peripheral" fat storage and BAT thermogenesis but did not induce hepatic steatosis and NASH.

  15. Long-term tobacco plantation induces soil acidification and soil base cation loss.

    Science.gov (United States)

    Zhang, Yuting; He, Xinhua; Liang, Hong; Zhao, Jian; Zhang, Yueqiang; Xu, Chen; Shi, Xiaojun

    2016-03-01

    Changes in soil exchangeable cations relative to soil acidification are less studied particularly under long-term cash crop plantation. This study investigated soil acidification in an Ali-Periudic Argosols after 10-year (2002-2012) long-term continuous tobacco plantation. Soils were respectively sampled at 1933 and 2143 sites in 2002 and 2012 (also 647 tobacco plants), from seven tobacco plantation counties in the Chongqing Municipal City, southwest China. After 10-year continuous tobacco plantation, a substantial acidification was evidenced by an average decrease of 0.20 soil pH unit with a substantial increase of soil sites toward the acidic status, especially those pH ranging from 4.5 to 5.5, whereas 1.93 kmol H(+) production ha(-1) year(-1) was mostly derived from nitrogen (N) fertilizer input and plant N uptake output. After 1 decade, an average decrease of 27.6 % total exchangeable base cations or of 0.20 pH unit occurred in all seven tobacco plantation counties. Meanwhile, for one unit pH decrease, 40.3 and 28.3 mmol base cations kg(-1) soil were consumed in 2002 and 2012, respectively. Furthermore, the aboveground tobacco biomass harvest removed 339.23 kg base cations ha(-1) year(-1) from soil, which was 7.57 times higher than the anions removal, leading to a 12.52 kmol H(+) production ha(-1) year(-1) as the main reason inducing soil acidification. Overall, our results showed that long-term tobacco plantation not only stimulated soil acidification but also decreased soil acid-buffering capacity, resulting in negative effects on sustainable soil uses. On the other hand, our results addressed the importance of a continuous monitoring of soil pH changes in tobacco plantation sites, which would enhance our understanding of soil fertility of health in this region. PMID:26566613

  16. Long-term Hg pollution induced Hg tolerance in the terrestrial isopod Porcellio scaber (Isopoda, Crustacea)

    International Nuclear Information System (INIS)

    The aim of our work was to assess the pollution-induced community tolerance (PICT) of isopod gut microbiota and pollution-induced isopod population tolerance (PIPT). Animals collected from a chronically Hg polluted and an unpolluted location were exposed for 14 days to 10 μg Hg/g dry food under laboratory conditions. The lysosomal membrane stability, hepatopancreas epithelium thickness, feeding activity and animal bacterial gut microbiota composition were determined. The results confirm the hypothesis that the response to short-term Hg exposure differs for animals from the Hg polluted and the unpolluted field locations. The animals and their gut microbiota from the Hg polluted location were less affected by Hg in a short-term feeding experiment than those from the unpolluted environment. We discuss the pollution-induced population tolerance of isopods and their gut microbiota as a measure of effects of long-term environmental pollution. The ecological consequences of such phenomena are also discussed. - Isopods (Porcellio scaber) as well as their bacterial gut community from a mercury-polluted site are mercury tolerant

  17. Long-term Hg pollution induced Hg tolerance in the terrestrial isopod Porcellio scaber (Isopoda, Crustacea)

    Energy Technology Data Exchange (ETDEWEB)

    Lapanje, A. [University of Ljubljana, Biotechnical Faculty, Department of Biology, Vecna pot 111, 1000 Ljubljana (Slovenia); Institute of Physical Biology, Veliko Mlacevo 59, 1290 Grosuplje (Slovenia)], E-mail: ales.lapanje@bf.uni-lj.si; Drobne, D. [University of Ljubljana, Biotechnical Faculty, Department of Biology, Vecna pot 111, 1000 Ljubljana (Slovenia); Nolde, N. [Institute Jozef Stefan, Department of Environmental Sciences, Jamova 39, 1000 Ljubljana (Slovenia); Valant, J. [University of Ljubljana, Biotechnical Faculty, Department of Biology, Vecna pot 111, 1000 Ljubljana (Slovenia); Muscet, B. [Institute of Physical Biology, Veliko Mlacevo 59, 1290 Grosuplje (Slovenia); Leser, V. [University of Ljubljana, Biotechnical Faculty, Department of Biology, Vecna pot 111, 1000 Ljubljana (Slovenia); Rupnik, M. [Institute of Public Health, Prvomajska 1, 2000 Maribor (Slovenia); Faculty of Medicine, University of Maribor, Slomskov trg 15, 2000 Maribor (Slovenia)

    2008-06-15

    The aim of our work was to assess the pollution-induced community tolerance (PICT) of isopod gut microbiota and pollution-induced isopod population tolerance (PIPT). Animals collected from a chronically Hg polluted and an unpolluted location were exposed for 14 days to 10 {mu}g Hg/g dry food under laboratory conditions. The lysosomal membrane stability, hepatopancreas epithelium thickness, feeding activity and animal bacterial gut microbiota composition were determined. The results confirm the hypothesis that the response to short-term Hg exposure differs for animals from the Hg polluted and the unpolluted field locations. The animals and their gut microbiota from the Hg polluted location were less affected by Hg in a short-term feeding experiment than those from the unpolluted environment. We discuss the pollution-induced population tolerance of isopods and their gut microbiota as a measure of effects of long-term environmental pollution. The ecological consequences of such phenomena are also discussed. - Isopods (Porcellio scaber) as well as their bacterial gut community from a mercury-polluted site are mercury tolerant.

  18. Protein synthesis required for long-term memory is induced by PKC activation on days before associative learning

    OpenAIRE

    Alkon, Daniel L.; Epstein, Herman; Kuzirian, Alan; Bennett, M. Catherine; Nelson, Thomas J.

    2005-01-01

    Protein synthesis has long been known to be required for associative learning to consolidate into long-term memory. Here we demonstrate that PKC isozyme activation on days before training can induce the synthesis of proteins necessary and sufficient for subsequent long-term memory consolidation. Bryostatin (Bryo), a macrolide lactone with efficacy in subnanomolar concentrations and a potential therapeutic for Alzheimer's disease, is a potent activator of PKC, some of whose isozymes undergo pr...

  19. Orexin A induces bidirectional modulation of synaptic plasticity: Inhibiting long-term potentiation and preventing depotentiation.

    Science.gov (United States)

    Lu, Guan-Ling; Lee, Chia-Hsu; Chiou, Lih-Chu

    2016-08-01

    The orexin system consists of two peptides, orexin A and B and two receptors, OX1R and OX2R. It is implicated in learning and memory regulation while controversy remains on its role in modulating hippocampal synaptic plasticity in vivo and in vitro. Here, we investigated effects of orexin A on two forms of synaptic plasticity, long-term potentiation (LTP) and depotentiation of field excitatory postsynaptic potentials (fEPSPs), at the Schaffer Collateral-CA1 synapse of mouse hippocampal slices. Orexin A (≧30 nM) attenuated LTP induced by theta burst stimulation (TBS) in a manner antagonized by an OX1R (SB-334867), but not OX2R (EMPA), antagonist. Conversely, at 1 pM, co-application of orexin A prevented the induction of depotentiation induced by low frequency stimulation (LFS), i.e. restoring LTP. This re-potentiation effect of sub-nanomolar orexin A occurred at LFS of 1 Hz, but not 2 Hz, and with LTP induced by either TBS or tetanic stimulation. It was significantly antagonized by SB-334867, EMPA and TCS-1102, selective OX1R, OX2R and dual OXR antagonists, respectively, and prevented by D609, SQ22536 and H89, inhibitors of phospholipase C (PLC), adenylyl cyclase (AC) and protein kinase A (PKA), respectively. LFS-induced depotentiation was antagonized by blockers of NMDA, A1-adenosine and type 1/5 metabotropic glutamate (mGlu1/5) receptors, respectively. However, orexin A (1 pM) did not affect chemical-induced depotentiation by agonists of these receptors. These results suggest that orexin A bidirectionally modulates hippocampal CA1 synaptic plasticity, inhibiting LTP via OX1Rs at moderate concentrations while inducing re-potentiation via OX1Rs and OX2Rs, possibly through PLC and AC-PKA signaling at sub-nanomolar concentrations. PMID:26965217

  20. Low-frequency stimulation induces long-term depression and slow onset long-term potentiation at perforant path-dentate gyrus synapses in vivo.

    Science.gov (United States)

    Gonzalez, Jossina; Morales, Isaiah S; Villarreal, Desiree M; Derrick, Brian E

    2014-03-01

    The expression of homosynaptic long-term depression (LTD) is thought to mediate a crucial role in sustaining memory function. Our in vivo investigations of LTD expression at lateral (LPP) and medial perforant path (MPP) synapses in the dentate gyrus (DG) corroborate prior demonstrations that PP-DG LTD is difficult to induce in intact animals. In freely moving animals, LTD expression occurred inconsistently among LPP-DG and MPP-DG responses. Interestingly, following acute electrode implantation in anesthetized rats, low-frequency stimulation (LFS; 900 pulses, 1 Hz) promotes slow-onset LTP at both MPP-DG and LPP-DG synapses that utilize distinct induction mechanisms. Systemic administration of the N-methyl-d-aspartate (NMDA) receptor antagonist (+/-)-cyclopiperidine-6-piperiperenzine (CPP; 10 mg/kg) 90 min before LFS selectively blocked MPP-DG but not LPP-DG slow onset LTP, suggesting MPP-DG synapses express a NMDA receptor-dependent slow onset LTP whereas LPP-DG slow onset LTP induction is NMDA receptor independent. In experiments where paired-pulse LFS (900 paired pulses, 200-ms paired-pulse interval) was used to induce LTD, paired-pulse LFS of the LPP resulted in rapid onset LTP of DG responses, whereas paired-pulse LFS of the MPP induced slow onset LTP of DG responses. Although LTD observations were very rare following acute electrode implantation in anesthetized rats, LPP-DG LTD was demonstrated in some anesthetized rats with previously implanted electrodes. Together, our data indicate in vivo PP-DG LTD expression is an inconsistent phenomenon that is primarily observed in recovered animals, suggesting perturbation of the dentate through surgery-related tissue trauma influences both LTD incidence and LTP induction at PP-DG synapses in vivo. PMID:24335215

  1. Long term, continuous exposure to panobinostat induces terminal differentiation and long term survival in the TH-MYCN neuroblastoma mouse model.

    Science.gov (United States)

    Waldeck, Kelly; Cullinane, Carleen; Ardley, Kerry; Shortt, Jake; Martin, Ben; Tothill, Richard W; Li, Jason; Johnstone, Ricky W; McArthur, Grant A; Hicks, Rodney J; Wood, Paul J

    2016-07-01

    Neuroblastoma is the most common extra-cranial malignancy in childhood and accounts for ∼15% of childhood cancer deaths. Amplification of MYCN in neuroblastoma is associated with aggressive disease and predicts for poor prognosis. Novel therapeutic approaches are therefore essential to improving patient outcomes in this setting. The histone deacetylases are known to interact with N-Myc and regulate numerous cellular processes via epigenetic modulation, including differentiation. In this study, we used the TH-MYCN mouse model of neuroblastoma to investigate the antitumor activity of the pan-HDAC inhibitor, panobinostat. In particular we sought to explore the impact of long term, continuous panobinostat exposure on the epigenetically driven differentiation process. Continuous treatment of tumor bearing TH-MYCN transgenic mice with panobinostat for nine weeks led to a significant improvement in survival as compared with mice treated with panobinostat for a three-week period. Panobinostat induced rapid tumor regression with no regrowth observed following a nine-week treatment period. Initial tumor response was associated with apoptosis mediated via upregulation of BMF and BIM. The process of terminal differentiation of neuroblastoma into benign ganglioneuroma, with a characteristic increase in S100 expression and reduction of N-Myc expression, occurred following prolonged exposure to the drug. RNA-sequencing analysis of tumors from treated animals confirmed significant upregulation of gene pathways associated with apoptosis and differentiation. Together our data demonstrate the potential of panobinostat as a novel therapeutic strategy for high-risk neuroblastoma patients. PMID:26914605

  2. TBTC induces adipocyte differentiation in human bone marrow long term culture

    International Nuclear Information System (INIS)

    Organotins are widely used in agriculture and the chemical industry, causing persistent and widespread pollution. Organotins may affect the brain, liver and immune system and eventually human health. Recently, it has been shown that tri-butyltin (TBT) interacts with nuclear receptors PPARγ (peroxisome proliferator-activated receptor γ) and RXR (retinoid x receptor) leading to adipocyte differentiation in the 3T3 cell line. Since adipocytes are known to influence haematopoiesis, for instance through the expression of cytokines and adhesion molecules, it was considered of interest to further study the adipocyte-stimulating effect of TBTC in human bone marrow cultures. Nile Red spectrofluorimetric analysis showed a significant increase of adipocytes in TBTC-treated cultures after 14 days of long term culture. Real-time PCR and Western blot analysis confirmed the high expression of the specific adipocyte differentiation marker aP2 (adipocyte-specific fatty acid binding protein). PPARγ, but not RXR, mRNA was increased after 24 h and 48 h exposure. TBTC also induced a decrease in a number of chemokines, interleukins, and growth factors. Also the expression of leptin, a hormone involved in haematopoiesis, was down regulated by TBTC treatment. It therefore appears that TBTC induced adipocyte differentiation, whilst reducing a number of haematopoietic factors. This study indicates that TBTC may interfere in the haematopoietic process through an alteration of the stromal layer and cytokine homeostasis

  3. Dispersal limitation induces long-term biomass collapse in overhunted Amazonian forests.

    Science.gov (United States)

    Peres, Carlos A; Emilio, Thaise; Schietti, Juliana; Desmoulière, Sylvain J M; Levi, Taal

    2016-01-26

    Tropical forests are the global cornerstone of biological diversity, and store 55% of the forest carbon stock globally, yet sustained provisioning of these forest ecosystem services may be threatened by hunting-induced extinctions of plant-animal mutualisms that maintain long-term forest dynamics. Large-bodied Atelinae primates and tapirs in particular offer nonredundant seed-dispersal services for many large-seeded Neotropical tree species, which on average have higher wood density than smaller-seeded and wind-dispersed trees. We used field data and models to project the spatial impact of hunting on large primates by ∼ 1 million rural households throughout the Brazilian Amazon. We then used a unique baseline dataset on 2,345 1-ha tree plots arrayed across the Brazilian Amazon to model changes in aboveground forest biomass under different scenarios of hunting-induced large-bodied frugivore extirpation. We project that defaunation of the most harvest-sensitive species will lead to losses in aboveground biomass of between 2.5-5.8% on average, with some losses as high as 26.5-37.8%. These findings highlight an urgent need to manage the sustainability of game hunting in both protected and unprotected tropical forests, and place full biodiversity integrity, including populations of large frugivorous vertebrates, firmly in the agenda of reducing emissions from deforestation and forest degradation (REDD+) programs. PMID:26811455

  4. Glutamate-induced long-term potentiation enhances spontaneous EPSC amplitude but not frequency.

    Science.gov (United States)

    Cormier, R J; Kelly, P T

    1996-05-01

    1. Many examples of long-term potentiation (LPT) are induced by repetitive electrical stimulation of presynaptic axons. LTP also is induced by direct glutamate iontophoresis (1 M, 1-2 microA, 10 s) onto postsynaptic neurons in hippocampal slices without evoked presynaptic stimulation; this form of LTP is called "ionto-LTP". The studies herein test the hypothesis that ionto-LTP is expressed primarily through postsynaptic mechanisms. 2. Whole cell recordings were used to examine the amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in CA1 pyramidal neurons. sEPSCs were composed of an equal mixture of tetrodotoxin (TTX)-insensitive miniature EPSCs and EPSCs that appeared to result from spontaneous action potentials (i.e., TTX-sensitive EPSCs). The detection of all sEPSCs was virtually eliminated by 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM), suggesting that sEPSCs were glutamate-mediated synaptic events. 3. Changes in the amplitude and frequency of sEPSCs were examined during the expression of ionto-LTP to obtain new information about the cellular location of mechanisms involved in synaptic plasticity. Our findings show that ionto-LTP expression results in increased sEPSC amplitude in the absence of lasting increases in sEPSC frequency. 4. Potentiation of sEPSC amplitude without changes in sEPSC frequency has been previously interpreted to be due to postsynaptic mechanisms. Although this interpretation is supported by findings from peripheral synapses, its application to the central nervous system is unclear. We have considered alternative mechanisms. Models based on increased release probability for action potential dependent transmitter release appeared insufficient to explain our results. The most straightforward interpretation of our results is that LTP induced by glutamate iontophoresis on dendrites of CA1 pyramidal neurons is mediated largely by postsynaptic changes. PMID:8734590

  5. Exposure of mouse to high gravitation forces induces long-term potentiation in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Ishii M

    2004-06-01

    Full Text Available The central nervous system is highly plastic and has been shown to undergo both transient and chronic adaptive changes in response to environmental influences. The purpose of this study was to investigate the effect of hypergravic field on long-term potentiation (LTP in the mouse hippocampus. Exposure of mice to 4G fields for 48 h had no effect on input-output coupling during extracellular stimulation of Schaffer collaterals and paired pulse facilitation, suggesting that the hypergravic exposure had no detrimental effect on basal neurotransmission in the hippocampus. However, the exposure to 4G fields for 48 h significantly induced LTP compared with the control mouse hippocampus. In contrast, no significant changes of late-phase LTP (L-LTP were found in the hippocampi of mice exposed to the hypergravic field. Exposure of mice to 4G fields for 48 h enhanced AMPA receptor phosphorylation but not cyclic AMP-responsive element binding protein (CREB phosphorylation. These results suggest that exposure to hyperdynamic fields influences the synaptic plasticity in the hippocampus.

  6. Long-term modelling for estimation of man-induced environmental risks

    International Nuclear Information System (INIS)

    Full text: As a part of the EU coordination action project ENVIRO-RISKS the long-term regional and transboundary atmospheric transport, dispersion, and deposition of atmospheric pollutants is investigated. Focus is on pollutants originating at nuclear and chemical risk sites of the NIS countries. Potential sources of atmospheric pollution include chemical and metallurgical enterprises and smelters, former testing polygons of nuclear weapons, and nuclear plants and facilities. These are situated within territories of Kazakhstan, Ukraine, and Russia (the Siberian, Ural, Krasnoyarsk, and Kola regions). The atmospheric pollutants considered are radionuclides such as Cs-137, I-131, and Sr-90 as well as sulphates and heavy metals. The Danish Emergency Model for Atmosphere (DERMA) is employed for simulations using 3D meteorological fields from the European Center for Medium-range Weather Forecasts. The modeled concentration and deposition fields of atmospheric pollutants are used as input into further collaborative studies to estimate the man-induced environmental risks from regionally and remotely located potential sources with a focus on Siberian territories. The temporal and spatial variability of these fields and the probabilities and contribution of removal during atmospheric transport are evaluated. Possible approaches for further GIS integration and use of obtained results are discussed with respect to estimation of man-received doses and risks, impact on environment with a focus on forests, applicability for integrated systems for regional environmental monitoring and management, and others. (author)

  7. Long-Term Effects of Induced Hypothermia on Local and Systemic Inflammation - Results from a Porcine Long-Term Trauma Model.

    Directory of Open Access Journals (Sweden)

    K Horst

    Full Text Available Hypothermia has been discussed as playing a role in improving the early phase of systemic inflammation. However, information on the impact of hypothermia on the local inflammatory response is sparse. We therefore investigated the kinetics of local and systemic inflammation in the late posttraumatic phase after induction of hypothermia in an established porcine long-term model of combined trauma.Male pigs (35 ± 5kg were mechanically ventilated and monitored over the study period of 48 h. Combined trauma included tibia fracture, lung contusion, liver laceration and pressure-controlled hemorrhagic shock (MAP < 30 ± 5 mmHg for 90 min. After resuscitation, hypothermia (33°C was induced for a period of 12 h (HT-T group with subsequent re-warming over a period of 10 h. The NT-T group was kept normothermic. Systemic and local (fracture hematoma cytokine levels (IL-6, -8, -10 and alarmins (HMGB1, HSP70 were measured via ELISA.Severe signs of shock as well as systemic and local increases of pro-inflammatory mediators were observed in both trauma groups. In general the local increase of pro- and anti-inflammatory mediator levels was significantly higher and prolonged compared to systemic concentrations. Induction of hypothermia resulted in a significantly prolonged elevation of both systemic and local HMGB1 levels at 48 h compared to the NT-T group. Correspondingly, local IL-6 levels demonstrated a significantly prolonged increase in the HT-T group at 48 h.A prolonged inflammatory response might reduce the well-described protective effects on organ and immune function observed in the early phase after hypothermia induction. Furthermore, local immune response also seems to be affected. Future studies should aim to investigate the use of therapeutic hypothermia at different degrees and duration of application.

  8. Tumor necrosis factor-alpha-induced apoptosis in hepatocytes in long-term culture.

    OpenAIRE

    Bour, E. S.; Ward, L. K.; Cornman, G. A.; Isom, H. C.

    1996-01-01

    Apoptosis occurs naturally in the liver and increases in specific pathogenic processes. We previously described the use of a chemically defined medium supplemented with epidermal growth factor and dimethylsulfoxide to maintain rat hepatocytes in a highly differentiated state for more than 30 days (long-term culture). In this study, we showed that hepatocytes in long-term dimethylsulfoxide culture have definite advantages over using cells in short-term culture (cells in culture for 2 to 4 days...

  9. Long-term Evaluation of Radiation-Induced Optic Neuropathy After Single-Fraction Stereotactic Radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Leavitt, Jacqueline A., E-mail: leavitt.jacqueline@mayo.edu [Department of Ophthalmology, Mayo Clinic and Foundation, Rochester, Minnesota (United States); Stafford, Scott L. [Department of Radiation Oncology, Mayo Clinic and Foundation, Rochester, Minnesota (United States); Link, Michael J. [Department of Neurosurgery, Mayo Clinic and Foundation, Rochester, Minnesota (United States); Pollock, Bruce E. [Department of Radiation Oncology, Mayo Clinic and Foundation, Rochester, Minnesota (United States); Department of Neurosurgery, Mayo Clinic and Foundation, Rochester, Minnesota (United States)

    2013-11-01

    Purpose: To determine the long-term risk of radiation-induced optic neuropathy (RION) in patients having single-fraction stereotactic radiosurgery (SRS) for benign skull base tumors. Methods and Materials: Retrospective review of 222 patients having Gamma Knife radiosurgery for benign tumors adjacent to the anterior visual pathway (AVP) between 1991 and 1999. Excluded were patients with prior or concurrent external beam radiation therapy or SRS. One hundred twenty-nine patients (58%) had undergone previous surgery. Tumor types included confirmed World Health Organization grade 1 or presumed cavernous sinus meningioma (n=143), pituitary adenoma (n=72), and craniopharyngioma (n=7). The maximum dose to the AVP was ≤8.0 Gy (n=126), 8.1-10.0 Gy (n=39), 10.1-12.0 Gy (n=47), and >12 Gy (n=10). Results: The mean clinical and imaging follow-up periods were 83 and 123 months, respectively. One patient (0.5%) who received a maximum radiation dose of 12.8 Gy to the AVP developed unilateral blindness 18 months after SRS. The chance of RION according to the maximum radiation dose received by the AVP was 0 (95% confidence interval [CI] 0-3.6%), 0 (95% CI 0-10.7%), 0 (95% CI 0-9.0%), and 10% (95% CI 0-43.0%) for patients receiving ≤8 Gy, 8.1-10.0 Gy, 10.1-12.0 Gy, and >12 Gy, respectively. The overall risk of RION in patients receiving >8 Gy to the AVP was 1.0% (95% CI 0-6.2%). Conclusions: The risk of RION after single-fraction SRS in patients with benign skull base tumors who have no prior radiation exposure is very low if the maximum dose to the AVP is ≤12 Gy. Physicians performing single-fraction SRS should remain cautious when treating lesions adjacent to the AVP, especially when the maximum dose exceeds 10 Gy.

  10. Role of "Aplysia" Cell Adhesion Molecules during 5-HT-Induced Long-Term Functional and Structural Changes

    Science.gov (United States)

    Han, Jin-Hee; Lim, Chae-Seok; Lee, Yong-Seok; Kandel, Eric R.; Kaang, Bong-Kiun

    2004-01-01

    We previously reported that five repeated pulses of 5-HT lead to down-regulation of the TM-apCAM isoform at the surface of "Aplysia" sensory neurons (SNs). We here examined whether apCAM down-regulation is required for 5-HT-induced long-term facilitation. We also analyzed the role of the cytoplasmic and extracellular domains by overexpressing…

  11. Long-Term Effects of Induced Hypothermia on Local and Systemic Inflammation - Results from a Porcine Long-Term Trauma Model

    OpenAIRE

    Horst, K.; Eschbach, D.; Pfeifer, R.; Relja, B; Sassen, M.; T. Steinfeldt; Wulf, H; N Vogt; Frink, M.; Ruchholtz, S.; Pape, H. C.; F. Hildebrand

    2016-01-01

    Background Hypothermia has been discussed as playing a role in improving the early phase of systemic inflammation. However, information on the impact of hypothermia on the local inflammatory response is sparse. We therefore investigated the kinetics of local and systemic inflammation in the late posttraumatic phase after induction of hypothermia in an established porcine long-term model of combined trauma. Materials & Methods Male pigs (35 ± 5kg) were mechanically ventilated and monitored ove...

  12. Inflammatory Mediators in Induced Sputum and Airway Hyperresponsiveness in Cough Variant Asthma during Long-Term Inhaled Corticosteroid Treatment

    OpenAIRE

    Meixuan Liu; Kaixiong Liu; Ning Zhu; Jingwen Xia; Xiaodong Chen

    2012-01-01

    Objective. This study aimed to investigate improvements in inflammatory mediator levels in induced sputum and airway hyperresponsiveness (AHR) in cough variant asthma (CVA) during long-term inhaled corticosteroid (ICS) treatment. Patients and Methods. Patients with CVA ( = 3 5 ) and classic asthma ( = 2 6 ) and healthy subjects ( = 2 4 ) were recruited into this study. All patients were treated with budesonide (400 μg/day). Measurement of inflammatory mediators in induced sputum and PD2...

  13. Long-term fatty liver-induced insulin resistance in orotic acid-induced nonalcoholic fatty liver rats.

    Science.gov (United States)

    Han, Xiuqing; Liu, Chunhua; Xue, Yong; Wang, Jingfeng; Xue, Changhu; Yanagita, Teruyoshi; Gao, Xiang; Wang, Yuming

    2016-01-01

    We investigated whether fatty liver preceded insulin resistance or vice versa using a long-term orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model without the confounding effects of obesity and hyperlipidemia and explored the role of the liver in insulin resistance. Male Wistar rats were fed with or without OA supplementation for 30, 60, and 90 days. The NAFLD group showed increased liver lipid at 30, 60, and 90 days; glucose intolerance was noted at 60 and 90 days. Furthermore, partial liver proteins and gene expressions related to upstream signaling of insulin were decreased. However, the liver glycogen content was elevated, and gluconeogenesis genes expressions were obviously decreased at 90 days. The occurrence of fatty liver preceded insulin resistance in OA-induced NAFLD without the interference of obesity and hyperlipidemia, and hepatic insulin resistance may not play a conclusive role in insulin resistance in this model. PMID:26775542

  14. The natural history of interferon-α induced thyroiditis in chronic hepatitis c patients: a long term study

    OpenAIRE

    Tran Huy A; Jones Tracey L; Ianna Elizabeth A; Reeves Glenn EM

    2011-01-01

    Abstract Background Autoimmune thyroid disease is a common complication of patients with chronic hepatitis C undergoing combination pegylated interferon-α and ribavirin treatment. A small proportion develops interferon-induced thyroiditis of which the long term natural history is unknown and how it compares with de novo thyroiditis. The aim of the study is to determine the natural history of thyroid disease including antibody profile in this particular setting 36 months from the completion of...

  15. Long-term experience of hyperbaric oxygen therapy for refractory radio- or chemotherapy-induced haemorrhagic cystitis

    OpenAIRE

    Degener, Stephan; Pohle, Alexander; Strelow, Hartmut; Mathers, Michael J.; Zumbé, Jürgen; Roth, Stephan; Brandt, Alexander S

    2015-01-01

    Background Radiotherapy and cyclophosphamide-induced haemorrhagic cystitis are rare but severe complications occurring in 3–6% of patients. Hyperbaric oxygen treatment (HBOT) has been demonstrated to be an effective treatment for haematuria not responding to conventional management. Only very few data exist for long-term follow-up after HBOT. Methods We retrospectively reviewed 15 patients referred for HBOT for haemorrhagic cystitis (HC). HBOT was performed for 130 min/day at a pressure of 2....

  16. Effect of MK-801 on methamphetamine-induced dopaminergic neurotoxicity: long-term attenuation of methamphetamine-induced dopamine release

    International Nuclear Information System (INIS)

    Repeated administration of methamphetamine (METH) produces high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. The effect of MK-801, a noncompetitive N-methyl-D-aspartate receptor antagonist, on METH-induced changes in DA transporter (DAT) and DA release evoked by an acute METH challenge was evaluated in rodent striatum using [3H] WIN 38,428 ex vivo auto-radiography and in vivo microdialysis. Four injections of METH (10 mg/kg, i.p.), each given 2 h apart, produced 71% decrease in DAT levels in mouse striatum 3 d after administration. Pretreatment with MK-801 (2.5 g/kg, i.p.) 15 min before each of the four METH injections protected completely against striatal DAT depletions. Four injections of MK-801 alone did not significantly change striatal DAT levels. Striatal DA release evoked by an acute METH challenge (4mg/kg, i.p.) at 3 d after repeated administration of METH in rats was decreased but significant compared with controls, which was attenuated by repeated pretreatment with MK-801. Also, repeated injections of MK-801 alone attenuated acute METH-induced striatal DA release 3 d after administration. These results suggest that repeated administration of MK-801 may exert a preventive effect against METH-induced DA terminal injury through long-term attenuation of DA release induced by METH and other stimuli

  17. Propofol, but not etomidate, increases corticosterone levels and induces long-term alteration in hippocampal synaptic activity in neonatal rats.

    Science.gov (United States)

    Xu, Changqing; Seubert, Christoph N; Gravenstein, Nikolaus; Martynyuk, Anatoly E

    2016-04-01

    Animal studies provide strong evidence that general anesthetics (GAs), administered during the early postnatal period, induce long-term cognitive and neurological abnormalities. Because the brain growth spurt in rodents is delayed compared to that in humans, a fundamental question is whether the postnatal human brain is similarly vulnerable. Sevoflurane and propofol, GAs that share positive modulation of the gamma-aminobutyric acid type A receptor (GABAAR) function cause marked increase in corticosterone levels and induce long-term developmental alterations in synaptic activity in rodents. If synaptogenesis is affected, investigation of mechanisms of the synaptic effects of GAs is of high interest because synaptogenesis in humans continues for several years after birth. Here, we compared long-term synaptic effects of etomidate with those of propofol. Etomidate and propofol both positively modulate GABAAR activity, but in contrast to propofol, etomidate inhibits the adrenal synthesis of corticosterone. Postnatal day (P) 4, 5, or 6 rats received five injections of etomidate, propofol, or vehicle control during 5h of maternal separation. Endocrine effects of the anesthetics were evaluated by measuring serum levels of corticosterone immediately after anesthesia or maternal separation. The frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs) in hippocampal CA1 pyramidal neurons were measured at P24-40 and P≥80. Only propofol caused a significant increase in serum corticosterone levels (F(4.26)=17.739, P<0.001). In contrast to increased frequency of mIPSCs in the propofol group (F(4.23)=8.731, p<0.001), mIPSC activity in the etomidate group was not different from that in the vehicle groups. The results of this study together with previously published data suggest that anesthetic-caused increase in corticosterone levels is required for GABAergic GAs to induce synaptic effects in the form of a long-term increase in the frequency of hippocampal m

  18. Long-term management of vaccine-induced refractory ischemic dermatopathy in a Miniature Pinscher puppy.

    Science.gov (United States)

    Kim, Ha-Jung; Kang, Min-Hee; Kim, Ju-Won; Kim, Dae-Young; Park, Hee-Myung

    2011-09-01

    A 2-month-old intact female Miniature Pinscher puppy presented with footpad swelling and crusted pustules of ear pinnae. The dog had been vaccinated with a polyvalent canine vaccine 5 days prior to the onset of clinical signs. With the history of recent vaccination, the clinical presentation and the histopathological observations were suggestive of ischemic dermatopathy. Treatment involved oral prednisolone, azathioprine, and other immune modulating drugs, which did not work. Chlorambucil plus cyclosporine therapy was initiated for vigorous immune suppression after rush therapy using intravenous immunoglobulin. Clinical signs again gradually improved with no relapse or side effects, even at a 4-month follow-up. The case report is suggested ischemic dermatopathy refractory to conventional therapy and suggests effective approaches to long-term management of the disease. PMID:21566400

  19. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Kathrin Hemmer

    2014-09-01

    Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  20. Long-Term Effects of Induced Hypothermia on Local and Systemic Inflammation - Results from a Porcine Long-Term Trauma Model

    Science.gov (United States)

    Horst, K.; Eschbach, D.; Pfeifer, R.; Relja, B.; Sassen, M.; Steinfeldt, T.; Wulf, H.; Vogt, N.; Frink, M.; Ruchholtz, S.; Pape, H. C.; Hildebrand, F.

    2016-01-01

    Background Hypothermia has been discussed as playing a role in improving the early phase of systemic inflammation. However, information on the impact of hypothermia on the local inflammatory response is sparse. We therefore investigated the kinetics of local and systemic inflammation in the late posttraumatic phase after induction of hypothermia in an established porcine long-term model of combined trauma. Materials & Methods Male pigs (35 ± 5kg) were mechanically ventilated and monitored over the study period of 48 h. Combined trauma included tibia fracture, lung contusion, liver laceration and pressure-controlled hemorrhagic shock (MAP fracture hematoma) cytokine levels (IL-6, -8, -10) and alarmins (HMGB1, HSP70) were measured via ELISA. Results Severe signs of shock as well as systemic and local increases of pro-inflammatory mediators were observed in both trauma groups. In general the local increase of pro- and anti-inflammatory mediator levels was significantly higher and prolonged compared to systemic concentrations. Induction of hypothermia resulted in a significantly prolonged elevation of both systemic and local HMGB1 levels at 48 h compared to the NT-T group. Correspondingly, local IL-6 levels demonstrated a significantly prolonged increase in the HT-T group at 48 h. Conclusion A prolonged inflammatory response might reduce the well-described protective effects on organ and immune function observed in the early phase after hypothermia induction. Furthermore, local immune response also seems to be affected. Future studies should aim to investigate the use of therapeutic hypothermia at different degrees and duration of application. PMID:27144532

  1. Liver cirrhosis induced by long-term administration of a daily low dose of amiodarone: A case report

    Institute of Scientific and Technical Information of China (English)

    Hiroki Oikawa; Kazuyuki Suzuki; Tomoyuki Masuda; Chihaya Maesawa; Ryo Sato; Kanta Oikawa; Hiroyuki Yamada; Seizo Oriso; Sadahide Ono; Akiko Yashima-Abo; Koji Kotani

    2005-01-01

    The anti-arrhythmic agent amiodarone (AD) is associated with numerous adverse effects, but serious liver disease is rare. The improved safety of administration of daily low doses of AD has already been established and this regimen is used for long-term medication. Nevertheless,asymptomatic continuous liver injury by AD may increase the risk of step-wise progression of non-alcoholic fatty liver disease. We present an autopsy case of AD-induced liver cirrhosis in a patient who had been treated with a low dose of AD (200 mg/d) daily for 84 mo. The patient was a 85-year-old male with a history of ischemic heart disease.Seven years after initiation of treatment with AD, he was admitted with cardiac congestion. The total dose of AD was 528 g. Mild elevation of serum aminotransferase and hepatomegaly were present. Liver biopsy specimens revealed cirrhosis, and under electron microscopy numerous lysosomes with electron-dense, whorled, lamellar inclusions characteristic of a secondary phospholipidosis were observed. Initially, withdrawal of AD led to a slight improvement of serum aminotransferase levels, but unfortunately his general condition deteriorated and he died from complications of pneumonia and renal failure.Long-term administration of daily low doses of AD carries the risk of progression to irreversible liver injury. Therefore,periodic examination of liver function and/or liver biopsy is required for the management of patients receiving long-term treatment with AD.

  2. Pulmonary Nocardiosis Induced by Long-Term Use of Steroids on a Bronchiectasis Backgroung

    Directory of Open Access Journals (Sweden)

    Levent Özdemir

    2015-03-01

    Full Text Available A 45-year-old male was assessed with the complaints of cough, sputum, fever, shortness of breath, tingling and burning in both legs. In his history, he had frequent hospitalizations and steroid use. Respiratory system examination revealed inspiratory and expiratory crackles on bilateral lower-middle zones and expiration rhoncus. Laboratory examination revealed leukocytosis and elevated CRP levels; serology for HIV was reported negative. Computed tomography showed diffuse interstitial pneumonia. Electromyography (EMG showed lower extremity muscle activation compatible with myopathy. Acid-fast bacilli was negative (three consecutive negative microscopy results and no reproduction was detected in the culture. Nocardia spp. growth was detected in sputum culture. According to the antibiogram results, he was treated with doxycycline, trimethoprim and sulfamethoxazole for 6 months. At the end of treatment, the lesions were found to be regressed on computed tomography. In conclusion, considering the high frequency of bronchiectasis in our country, the fact that nocardia may develop due to inappropriate long-term steroid use during an attack should be kept in mind.

  3. Long-term prognosis for transplant-free survivors of paracetamol-induced acute liver failure

    DEFF Research Database (Denmark)

    Jepsen, P; Schmidt, L E; Larsen, F S;

    2010-01-01

    The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown.......The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown....

  4. Long term evaluation of morphometric and ultrastructural changes of testes of alloxan-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Amélia Arcângela Teixeira Trindade

    2013-04-01

    Full Text Available PURPOSE: To evaluate in a long term the morphometric and ultrastructural changes in seminiferous tubules (ST of normal and diabetic rats, and to correlate any changes with animal age and diabetes duration. METHODS: Sixty male Wistar rats, three months-old, were randomly divided into two groups: 30 non-diabetic controls (N and 30 alloxan untreated diabetic (D. After one, six and 12 months of follow-up or diabetes induction rats were sacrificed and the testes examined. Morphometric measures of the ST were performed by digital imaging analysis. ST ultrastructure was analyzed by transmission electron microscopy. RESULTS: Sustained hyperglycemic state was observed in all diabetic rats throughout the study. Serum testosterone was also significantly decreased in these animals. The diameter, total area, epithelium area and epithelium thickness of ST were lower and tubular density was higher in diabetic animals. Diabetic rats also showed ultrastructural changes compromising the whole testis including germ-, Sertoli-, and Leydig cells, and also the mithocondria and cellular nuclei. Most frequent of these consisted of vacuolization and/or accumulation of lipid droplets and electron dense dark material in cell cytoplasm and/or in membranes, cellular degeneration, and apoptosis. Non-diabetic control rats also showed testicular lesions that resemble to the diabetic lesions, although much less severe and with later onset in life of these animals. CONCLUSION: Histopathological changes observed in testes of normal and diabetic rats are closely related to the animal age and/or duration of the hyperglycemic state, being progressively more severe in animals sacrificed belatedly. These changes may play an important role in male infertility observed in diabetic subjects.

  5. Long-Term Human Induced Impacts on Marajó Island Landscapes, Amazon Estuary

    Directory of Open Access Journals (Sweden)

    Denise Schaan

    2010-02-01

    Full Text Available Archaeology is a discipline that can offer a long term perspective on the impacts human societies have had on the environment. Landscape studies are critical for understanding these impacts, because they embrace a dialectical view regarding the relationship between humans and their immediate surroundings. Such studies are well suited to the Amazon basin, a region that has driven much media attention due to astonishing rates of deforestation in certain areas, with likely consequences on the planet’s climate, posing challenges to the survival of the human species for the coming decades. In fact, although much has been said about the impacts of contemporary societies on tropical forest environments, ancient landscape management practices have not yet been considered part of the equation. Thus far, we know that Amerindian societies have been actively transforming their surroundings for millennia. On the eve of European contact, large, complex societies were bringing about long-lasting transformations of landscapes throughout the basin. Conquest and colonization resulted in epidemics, enslavement, and changes to the indigenous economies that managed to survive the genocide. Afterwards, as colonizers would exploit traditional resources leading, in many instances, to their exhaustion, a huge quantity of information on sustainable ways of dealing with certain environments became lost. Traditional knowledge, however, still survives among certain indigenous, peasant (caboclo, and African-Brazilian populations. Documentation of surviving management practices together with the study of the archaeological record could provide valuable information for policy makers. This article examines historical transformations that took place on Marajó Island during the last two millennia and advocates the importance of archaeological research for understanding the historical ecology of landscape change. It is argued that ancient economic strategies, some still being

  6. Long-term effects of repeated social stress on the conditioned place preference induced by MDMA in mice.

    Science.gov (United States)

    García-Pardo, M P; Blanco-Gandía, M C; Valiente-Lluch, M; Rodríguez-Arias, M; Miñarro, J; Aguilar, M A

    2015-12-01

    Previous studies have demonstrated that social defeat stress increases the rewarding effects of psychostimulant drugs such as cocaine and amphetamine. In the present study we evaluated the long-term effects of repeated social defeat (RSD) on the rewarding effects of ±3,4-methylenedioxymethamphetamine (MDMA) hydrochloride in the conditioned place preference (CPP) paradigm. Adolescent and young adult mice were exposed to four episodes of social defeat (on PND 29-40 and PND 47-56, respectively) and were conditioned three weeks later with 1.25 or 10mg/kg i.p. of MDMA (experiment 1). The long-term effects of RSD on anxiety, social behavior and cognitive processes were also evaluated in adult mice (experiment 2). RSD during adolescence enhanced vulnerability to priming-induced reinstatement in animals conditioned with 1.25mg/kg of MDMA and increased the duration of the CPP induced by the 10mg/kg of MDMA. The latter effect was also observed after RSD in young adult mice, as well as an increase in anxiety-like behavior, an alteration in social interaction (reduction in attack and increase in avoidance/flee and defensive/submissive behaviors) and an impairment of maze learning. These results support the idea that RSD stress increases the rewarding effects of MDMA and induces long-term alterations in anxiety, learning and social behavior in adult mice. Thus, exposure to stress may increase the vulnerability of individuals to developing MDMA dependence, which is a factor to be taken into account in relation to the prevention and treatment of this disorder. PMID:26093344

  7. Long-term safety, efficacy, and patient acceptability of teriparatide in the management of glucocorticoid-induced osteoporosis

    Directory of Open Access Journals (Sweden)

    Dore RK

    2013-05-01

    Full Text Available Robin K DoreDavid Geffen School of Medicine, University of California, Los Angeles, CA, USAAbstract: Glucocorticoids are commonly prescribed medications to treat multiple diseases across many medical specialties. One of the most common yet largely unappreciated side effect of glucocorticoid use is increased risk of fracture. Many different therapies are indicated to prevent and treat this condition; many guidelines exist that suggest appropriate use of both glucocorticoids and the medications approved to prevent this common side effect of glucocorticoid therapy. Nevertheless, 30%–50% of patients on long-term glucocorticoid therapy sustain a fracture. Teriparatide, recombinant human parathyroid hormone (1–34, is a daily self-injectable therapy for 24 months approved for use in patients taking long-term glucocorticoids. Teriparatide has been shown to increase bone mineral density and reduce vertebral fracture risk in glucocorticoid-treated patients. Glucocorticoids have many adverse effects on bone that teriparatide has been shown to prevent or negate. Given the fact that preventive therapy for glucocorticoid-induced osteoporosis is often not prescribed, one wonders whether a daily self-injectable therapy for this condition would be prescribed by physicians and accepted by patients. This article reviews the epidemiology, pathophysiology, treatment, guidelines, and persistence data (when available for patients with glucocorticoid-induced osteoporosis treated with teriparatide.Keywords: glucocorticoid-induced osteoporosis, teriparatide, anabolic, PTH, parathyroid hormone

  8. Intrathecal rimantadine induces motor, proprioceptive, and nociceptive blockades in rats.

    Science.gov (United States)

    Tzeng, Jann-Inn; Wang, Jieh-Neng; Wang, Jhi-Joung; Chen, Yu-Wen; Hung, Ching-Hsia

    2016-04-01

    The purpose of the experiment was to evaluate the local anesthetic effect of rimantadine in spinal anesthesia. Rimantadine in a dose-dependent fashion was constructed after intrathecally injecting the rats with four different doses. The potency and duration of rimantadine were compared with that of the local anesthetic lidocaine at producing spinal motor, nociceptive, and proprioceptive blockades. We demonstrated that intrathecal rimantadine dose-dependently produced spinal motor, nociceptive, and proprioceptive blockades. On the 50% effective dose (ED50) basis, the ranks of potencies at inducing spinal motor, nociceptive, and proprioceptive blockades was lidocaine>rimantadine (Pspinal block duration produced by rimantadine was longer than that produced by lidocaine (Pspinal anesthesia when compared with lidocaine. PMID:26949181

  9. Striatal dopamine D2/3 receptor availability increases after long-term bariatric surgery-induced weight loss.

    Science.gov (United States)

    van der Zwaal, Esther M; de Weijer, Barbara A; van de Giessen, Elsmarieke M; Janssen, Ignace; Berends, Frits J; van de Laar, Arnold; Ackermans, Mariette T; Fliers, Eric; la Fleur, Susanne E; Booij, Jan; Serlie, Mireille J

    2016-07-01

    In several studies reduced striatal dopamine D2/3 receptor (D2/3R) availability was reported in obese subjects compared to lean controls. Whether this is a reversible phenomenon remained uncertain. We previously determined the short-term effect of Roux-en-Y gastric bypass surgery (RYGB) on striatal D2/3R availability (using [(123)I]IBZM SPECT) in 20 morbidly obese women. Striatal D2/3R availability was lower compared to controls at baseline, and remained unaltered after 6 weeks, despite significant weight loss. To determine whether long-term bariatric surgery-induced weight loss normalizes striatal D2/3R binding, we repeated striatal D2/3R binding measurements at least 2 years after RYGB in 14 subjects of the original cohort. In addition, we assessed long-term changes in body composition, eating behavior and fasting plasma levels of leptin, ghrelin, insulin and glucose. Mean body mass index declined from 46±7kg/m(2) to 32±6kg/m(2), which was accompanied by a significant increase in striatal D2/3R availability (p=0.031). Striatal D2/3R availability remained significantly reduced compared to the age-matched controls (BMI 22±2kg/m(2); p=0.01). Changes in striatal D2/3R availability did not correlate with changes in body weight/fat, insulin sensitivity, ghrelin or leptin levels. Scores on eating behavior questionnaires improved and changes in the General Food Craving Questionnaire-State showed a borderline significant correlation with changes in striatal D2/3R availability. These findings show that striatal D2/3R availability increases after long-term bariatric-surgery induced weight loss, suggesting that reduced D2/3R availability in obesity is a reversible phenomenon. PMID:27184782

  10. Symptomatic radiation-induced cardiac disease in long-term survivors of esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Iwahashi, Noriaki; Kosuge, Masami; Kimura, Kazuo [Division of Cardiology, Yokohama City University Medical Center, Yokohama (Japan); Sakamaki, Kentaro [Department of Biostatistics, Yokohama City University Medical Center, Yokohama (Japan); Kunisaki, Chikara [Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama (Japan); Ogino, Ichiro; Watanabe, Shigenobu

    2016-06-15

    To evaluate clinical and dosimetric factors retrospectively affecting the risk of symptomatic cardiac disease (SCD) in esophageal cancer patients treated with radiotherapy. A total of 343 patients with newly diagnosed esophageal cancer were managed with concurrent chemoradiotherapy or radiotherapy alone. Of these, 58 patients were followed at our hospital for at least 4 years. Median clinical follow-up was 79 months. Cardiac toxicity was determined by Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0. The maximum and mean doses to the heart and percentage of the volume were calculated from the dose-volume histograms. SCD manifested in 11 patients. The heart diseases included three pericardial effusions, one pericardial effusion with valvular disease and paroxysmal atrial tachycardia, three atrial fibrillations, one sinus tachycardia, one coronary artery disease, one chest pain with strongly suspected coronary artery disease, and one congestive heart failure. The actual incidence of SCD was 13.8 % at 5 years. Univariate and multivariate analyses of continuous variables revealed that the risk of developing an SCD depended on the volume of the heart receiving a dose greater than 45 Gy (V45), 50 Gy (V50), and 55 Gy (V55). No other clinical factors were found to influence the risk of SCD. For V45, V50, and V55, the lowest significant cutoff values were 15, 10, and 5 %, respectively. High-dose and large-volume irradiation of the heart increased the risk of SCD in long-term survivors. Using modern radiotherapy techniques, it is important to minimize the heart dose-volume parameters without reducing the tumor dose. (orig.) [German] Beurteilung von klinischen und dosimetrischen Faktoren, die mit Risiken eines retrospektiven Auftretens von symptomatischen Herzerkrankungen (SCD) bei Patienten zusammenhaengen, die aufgrund eines Oesophaguskarzinoms strahlentherapeutisch behandelt wurden. Insgesamt 343 Patienten mit neu diagnostiziertem Oesophaguskarzinom wurden mit

  11. Facial stimulation induces long-term depression at cerebellar molecular layer interneuron–Purkinje cell synapses in vivo in mice

    Directory of Open Access Journals (Sweden)

    De-Lai eQiu

    2015-06-01

    Full Text Available Cerebellar long-term synaptic plasticity has been proposed to provide a cellular mechanism for motor learning. Numerous studies have demonstrated the induction and mechanisms of synaptic plasticity at parallel fiber–Purkinje cell (PF–PC, parallel fiber–molecular layer interneurons (PF–MLI and mossy fiber–granule cell (MF–GC synapses, but no study has investigated sensory stimulation-evoked synaptic plasticity at MLI–PC synapses in the cerebellar cortex of living animals. We studied the expression and mechanism of MLI–PC GABAergic synaptic plasticity induced by a train of facial stimulation in urethane-anesthetized mice by cell-attached recordings and pharmacological methods. We found that 1 Hz, but not a 2 Hz or 4 Hz, facial stimulation induced a long-term depression (LTD of GABAergic transmission at MLI–PC synapses, which was accompanied with a decrease in the stimulation-evoked pause of spike firing in PCs, but did not induce a significant change in the properties of the sensory-evoked spike events of MLIs. The MLI–PC GABAergic LTD could be prevented by blocking cannabinoid type 1 (CB1 receptors, and could be pharmacologically induced by a CB1 receptor agonist. Additionally, 1 Hz facial stimulation delivered in the presence of a metabotropic glutamate receptor 1 (mGluR1 antagonist, JNJ16259685, still induced the MLI–PC GABAergic LTD, whereas blocking N-methyl-D-aspartate (NMDA receptors during 1 Hz facial stimulation abolished the expression of MLI–PC GABAergic LTD. These results indicate that sensory stimulation can induce an endocannabinoid (eCB-dependent LTD of GABAergic transmission at MLI–PC synapses via activation of NMDA receptors in cerebellar cortical Crus II in vivo in mice. Our results suggest that the sensory stimulation-evoked MLI–PC GABAergic synaptic plasticity may play a critical role in motor learning in animals.

  12. Vaccination against H5 avian influenza virus induces long-term humoral immune responses in flamingoes (Phoenicopterus spp.).

    Science.gov (United States)

    Fernández-Bellon, Hugo; Vergara-Alert, Júlia; Almagro, Vanessa; Rivas, Raquel; Sánchez, Azucena; Martínez, María Carmen; Majó, Natàlia; Busquets, Núria; Ramis, Antonio

    2016-06-01

    Avian influenza (AI) can represent a threat to endangered wild birds, as demonstrated with the H5N1 highly pathogenic AI (HPAI) outbreaks. Vaccination against AI using inactivated H5-vaccines has been shown to induce humoral immune response in zoo bird species. In this study, the long-term efficacy of H5-vaccination was evaluated in flamingoes from Barcelona Zoo. Specific H5-antibody titres were maintained at high levels (geometric mean titres ≥32) for over 7 years after vaccination, both against the H5N9 and H5N3 vaccine strains, as well as H5N3 and H5N1 reference strains. In addition the breadth of the immune response was also studied by testing antibody production against H1-, H3-, H4-, H7-, and H10-subtypes. It was observed that most flamingoes presented specific antibodies against H1 virus subtypes, but titres to the other HA-subtypes were rarely detected. We show that AI-vaccines can induce immunity lasting seven years in flamingoes, which suggests that vaccination can provide long term protection from HPAI outbreaks in zoo birds. PMID:27151883

  13. Episodic hypoxia induces long-term facilitation of upper airway muscle activity in spontaneously breathing anaesthetized rats.

    Science.gov (United States)

    Ryan, Stephen; Nolan, Philip

    2009-07-01

    We performed these experiments to determine if repeated exposure to episodic hypoxia induces long term facilitation (LTF) in anaesthetized spontaneously breathing rats. A previous study in spontaneously breathing rats was unable to demonstrate evidence of LTF with repeated hypoxia, but this may have been due to the low number of hypoxic episodes used. We hypothesized that with sufficient exposure, episodic hypoxia LTF of genioglossus (GG), hyoglossus (HG) and diaphragm (Dia) activities would be elicited. Experiments were performed in 24 anaesthetized spontaneously breathing rats with intact vagi. Peak and tonic GG, HG and Dia EMG activities were recorded before, during and for 1 h following exposure to eight (n = 8) or three (n = 8) episodes of isocapnic hypoxia ( = 0.1) each of 3 min duration. A third time control series was also performed with exposure to normoxia alone ( = 0.28, n = 8). Short-term potentiation of GG and HG muscle activity developed during the early period after repeated exposure to eight and three hypoxic episodes. LTF, however, occurred only after eight hypoxic episodes. This manifested as an increase in peak GG and Dia inspiratory muscle activity and tonic HG activity. LTF of respiratory breathing frequency was also induced, reflected by a reduction in inspiratory and expiratory time. These findings support our initial hypothesis that LTF in the anaesthetized, spontaneously breathing rat is dependent on the number of exposures to hypoxia and show that the responses to repetitive hypoxia are composed of both short and long-term facilitatory changes. PMID:19332489

  14. Physiological Changes Induced by Long Term Administration of Saccharin Compared with Aspartame to Male Albino Rats

    OpenAIRE

    Abdallah, Inas Z. A.

    2002-01-01

    Artificial sweeteners have been in use by food industries for a long time. Safety concerns raised about artificial sweeteners since they are widely used nowadays. The present work aims to study the possible changes in body weight, blood picture, liver functions, blood glucose and liver glycogen content as wel as histopathological changes induced in liver and urinary bladder of male albino rats after administration of two artificial sweeteners (saccharin or aspartame). Male rats were administe...

  15. Long-term in vivo polychlorinated biphenyl 126 exposure induces oxidative stress and alters proteomic profile on islets of Langerhans

    Science.gov (United States)

    Loiola, Rodrigo Azevedo; Dos Anjos, Fabyana Maria; Shimada, Ana Lúcia; Cruz, Wesley Soares; Drewes, Carine Cristiane; Rodrigues, Stephen Fernandes; Cardozo, Karina Helena Morais; Carvalho, Valdemir Melechco; Pinto, Ernani; Farsky, Sandra Helena

    2016-06-01

    It has been recently proposed that exposure to polychlorinated biphenyls (PCBs) is a risk factor to type 2 diabetes mellitus (DM2). We investigated this hypothesis using long-term in vivo PCB126 exposure to rats addressing metabolic, cellular and proteomic parameters. Male Wistar rats were exposed to PCB126 (0.1, 1 or 10 μg/kg of body weight/day; for 15 days) or vehicle by intranasal instillation. Systemic alterations were quantified by body weight, insulin and glucose tolerance, and blood biochemical profile. Pancreatic toxicity was measured by inflammatory parameters, cell viability and cycle, free radical generation, and proteomic profile on islets of Langerhans. In vivo PCB126 exposure enhanced the body weight gain, impaired insulin sensitivity, reduced adipose tissue deposit, and elevated serum triglycerides, cholesterol, and insulin levels. Inflammatory parameters in the pancreas and cell morphology, viability and cycle were not altered in islets of Langerhans. Nevertheless, in vivo PCB126 exposure increased free radical generation and modified the expression of proteins related to oxidative stress on islets of Langerhans, which are indicative of early β-cell failure. Data herein obtained show that long-term in vivo PCB126 exposure through intranasal route induced alterations on islets of Langerhans related to early end points of DM2.

  16. Case Reports Showing a Long-Term Effect of Subanesthetic Ketamine Infusion in Reducing l-DOPA-Induced Dyskinesias.

    Science.gov (United States)

    Sherman, Scott J; Estevez, Miguel; Magill, Ari B; Falk, Torsten

    2016-01-01

    Ketamine is an FDA-approved drug with a known safety profile. Low-dose subanesthetic intravenous ketamine infusion treatment has led to long-term reduction of treatment-resistant depression and of chronic pain states. We report on low-dose subanesthetic intravenous ketamine infusion treatment in Parkinson's disease (PD) patients by 5 case studies and show a long-lasting therapeutic benefit to reduce l-DOPA-induced dyskinesia (LID), improve on time, and reduce depression. Based on the literature we hypothesize that low-dose ketamine may act as a 'chemical deep brain stimulation', by desynchronizing hypersynchronous oscillatory brain activity, including in the basal ganglia and the motor cortex. The presented PD case reports indicate tolerability, safety and long-term beneficial effects of low-dose ketamine infusion that should be further investigated in a properly controlled prospective clinical trial for treatment of LID, as well as the prevalent nonmotor features pain and depression in PD patients. PMID:27293405

  17. Blood Volume Changes Induced By Low-Intensity Intradialytic Exercise in Long-Term Hemodialysis Patients.

    Science.gov (United States)

    Ookawara, Susumu; Miyazawa, Haruhisa; Ito, Kiyonori; Ueda, Yuichiro; Kaku, Yoshio; Hirai, Keiji; Hoshino, Taro; Mori, Honami; Yoshida, Izumi; Morishita, Yoshiyuki; Tabei, Kaoru

    2016-01-01

    Intradialytic exercise-induced blood volume (BV) reduction may cause intradialytic hypotension in hemodialysis (HD) patients. However, BV recovery time after intradialytic exercise remains unknown. Hemodialysis patients were recruited, and their relative BV change (%ΔBV) were measured with intradialytic exercise (n = 12). After confirming the linearity of %ΔBV for 30 min, patients exercised using a stationary cycle in the supine position. The target exercise intensity was a 10% increase in heart rate (HR), corresponding to relatively low-intensity exercise. Baseline %ΔBV (assumed baseline) were calculated for the 30 min before exercise using linear regression analysis. The mean intradialytic exercise start and end times after HD initiation were 93.0 ± 8.4 and 116.4 ± 8.3 min, respectively, a mean exercise duration of 23.5 ± 2.6 min. Percentage change in blood volume declined rapidly upon exercise initiation and gradually increased above the assumed baseline throughout HD. At the end of HD, %ΔBV in the exercise group was significantly higher than the assumed baseline (measured - assumed baseline %ΔBV: 2.17 ± 0.62%; p = 0.02). Intradialytic exercise with low intensity in the supine position attenuated ultrafiltration-induced BV reduction at the end of HD. Therefore, intradialytic exercise may prevent intradialytic hypotension during later HD, although its intensity was relatively low level. PMID:26720736

  18. Long-term allergen exposure induces adipose tissue inflammation and circulatory system injury.

    Science.gov (United States)

    Jung, Chien-Cheng; Su, Huey-Jen

    2016-05-01

    The purpose of this study was to study whether allergen exposure can induce inflammation and lower the anti-inflammation levels in serum and in adipose tissues, and further develop cardiovascular injury. Our data showed that heart rate was significantly higher in the OVA-challenged mice compared to control mice. Moreover, there were higher expressions of pro-inflammation genes in the OVA-challenged mice in adipose tissues, and the expressions of anti-inflammation genes were lower. The levels of inflammation mediators were associated in serum and adipose tissues. The level of circulatory injury lactate dehydrogenase was significantly associated with the levels of E-selectin, resistin and adiponectin in the serum. The hematoxylin and eosin and immunohistochemistry stains indicated the OVA-challenged mice had higher levels of inflammation. In summary, the current study demonstrated allergen exposure can cause cardiovascular injury, and inflammatory mediators in adipose tissues play an important role in the pathogenesis of cardiovascular injury. PMID:27004794

  19. Long-term studies of urease-induced crystallization in human urine.

    Science.gov (United States)

    Edin-Liljegren, A; Grenabo, L; Hedelin, H; Pettersson, S; Wang, Y H

    1994-07-01

    Urine samples were inoculated with viable Proteus mirabilis or purified Jack bean urease. The subsequent pH increase and crystallization were followed for 2 weeks. Particle formation was detected much earlier and at a lower pH in urines inoculated with Proteus, in which a higher end pH was also reached. The crystal configuration in bacteria and urease inoculated samples was different. Crystal aggregation was also much more pronounced in the Proteus mirabilis inoculated samples. The total precipitation was markedly increased in the Proteus mirabilis inoculated samples. The presence of live Proteus mirabilis thus has a profound influence on urease-induced crystallization in human urine. Despite the formation of rather large crystal aggregates in the Proteus-inoculated urines, no firm aggregates of a "prestone" type were observed. PMID:8201667

  20. Estimation of long-term salivary gland damage induced by radiotherapy

    International Nuclear Information System (INIS)

    A classification is proposed for estimating salivary gland damage induced by radiotherapy to the head and neck. The volume of salivary glands irradiated was evaluated, and their relative proportions of whole saliva output were calculated. Stimulated salivary flow rate was measured in 61 patients treated with radiotherapy for head and neck malignancies. A highly significant negative correlation was found between the classification of salivary gland damage and stimulated salivary flow rate. The volume of the major salivary glands irradiated seems to be the most important factor affecting the postirradiation salivary flow after a curative dose of radiotherapy. If possible, partial sparing of the salivary glands may help to keep the patient's salivary secretion at an acceptable level and promote protection against dental caries. Most patients irradiated to the head and neck, however, need an effective prophylactic programme for the rest of their lives in order to preserve their teeth. (orig.)

  1. Long Term Study of Protective Mechanisms of Human Adipose Derived Mesenchymal Stem Cells on Cisplatin Induced Kidney injury in Sprague-Dawley Rats

    OpenAIRE

    Elhusseini, Fatma M; Saad, Mohamed-Ahdy A.A; Anber, Nahla; Elghannam, Doaa; Sobh, Mohamed-Ahmed; ALSAYED, AZIZA; El-dusoky, Sara; SHEASHAA, HUSSEIN; Abdel-Ghaffar, Hassan; Sobh, Mohamed

    2016-01-01

    Background/Aims: Long-term evaluation of cisplatin induced nephrotoxicity and the probable renal protective activities of stem cells are lacking up until now. We evaluated the early and long-term role of human adipose derived mesenchymal stem cells (ADMSCs) in prevention or amelioration of cisplatin induced acute kidney injury (AKI) in Sprague-Dawley rats. For this, we determined the kidney tissue level of oxidative stress markers in conjugation with a renal histopathological scoring system o...

  2. TLR-2 activation induces regulatory T cells and long-term suppression of asthma manifestations in mice.

    Directory of Open Access Journals (Sweden)

    Martijn C Nawijn

    Full Text Available Asthma is a chronic inflammatory disease of the airways characterized by variable airway obstruction and airway hyperresponsiveness (AHR. The T regulatory (Treg cell subset is critically important for the regulation of immune responses. Adoptive transfer of Treg cells has been shown to be sufficient for the suppression of airway inflammation in experimental allergic asthma. Intervention strategies aimed at expanding the Treg cell population locally in the airways of sensitized individuals are therefore of high interest as a potential therapeutic treatment for allergic airway disease. Here, we aim to test whether long-term suppression of asthma manifestations can be achieved by locally expanding the Treg cell subset via intranasal administration of a TLR-2 agonist. To model therapeutic intervention aimed at expanding the endogenous Treg population in a sensitized host, we challenged OVA-sensitized mice by OVA inhalation with concomitant intranasal instillation of the TLR-2 agonist Pam3Cys, followed by an additional series of OVA challenges. Pam3Cys treatment induced an acute but transient aggravation of asthma manifestations, followed by a reduction or loss of AHR to methacholine, depending on the time between Pam3Cys treatment and OVA challenges. In addition, Pam3Cys-treatment induced significant reductions of eosinophils and increased numbers of Treg cells in the lung infiltrates. Our data show that, despite having adverse acute effects, TLR2 agonist treatment as a therapeutic intervention induces an expansion of the Treg cell population in the lungs and results in long-term protection against manifestation of allergic asthma upon subsequent allergen provocation. Our data indicate that local expansion of Tregs in allergic airway disease is an interesting therapeutic approach that warrants further investigation.

  3. Physiological Changes Induced by Long Term Administration of Saccharin Compared with Aspartame to Male Albino Rats

    Directory of Open Access Journals (Sweden)

    Inas Z.A. Abdallah

    2002-09-01

    Full Text Available Artificial sweeteners have been in use by food industries for a long time. Safety concerns raised about artificial sweeteners since they are widely used nowadays. The present work aims to study the possible changes in body weight, blood picture, liver functions, blood glucose and liver glycogen content as wel as histopathological changes induced in liver and urinary bladder of male albino rats after administration of two artificial sweeteners (saccharin or aspartame. Male rats were administered saccharin (50 mg/kg b.w. or aspartame (100 mg/kg b.w. daily by intragastric gavage for 14 weeks. The results revealed that both saccharin and aspartame provoked highly significant reduction in body weight gain %. Saccharin exerted highly significant reduction in haemoglobin (Hb level, haematocrit (Hct% and red blood cel s (RBCs count, while aspartame induced insignificant changes in al haematological parameters. Alanine aminotransferase (ALT and aspartate aminotransferase (AST activity levels were significantly increased with saccharin and aspartame. Alkaline phosphatase (ALP levels in serum showed slightly insignificant increase by saccharim administration, while aspartame caused a significant rise in ALP. Blood glucose level of rats given saccharin significantly dropped, while aspartame caused a significant elevation in blood glucose level. Liver glycogen content of rats given saccharin significantly increased, while aspartame caused a significant reduction in liver glycogen content. Microscopic examination of liver sections showed lymphocytic and macrophages infiltration of the portal traid in rats administered saccharin, while aspartame group showed no histopathological changes except slight hydropic degeneration of hepatocytes. Urinary bladder sections of rats administered saccharin revealed proliferation of the mucosal epithelial cel s into papil ary invaginated projections with highly vascularized connective tissue core and mononuclear inflammatory

  4. Long-term cadmium exposure induces anemia in rats through hypoinduction of erythropoietin in the kidneys

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, Hyogo [Department of Public Health, Fukushima Medical College, Fukushima (Japan); Sato, Masao [Department of Biomolecular Sciences, Institute of Biomedical Sciences, Fukushima Medical College, Fukushima (Japan); Konno, Nobuhiro [Department of Public Health, Fukushima Medical College, Fukushima (Japan); Fukushima, Masaaki [Department of Public Health, Fukushima Medical College, Fukushima (Japan)

    1996-11-01

    Cadmium (Cd), a highly toxic heavy metal, is distributed widely in the general environment of today. The characteristic clinical manifestations of chronic Cd intoxication include renal proximal tubular dysfunction, general osteomalacia with severe pains, and anemia. We have recently reported that the serum level of erythropoietin (EPO) remained low despite the severe anemia in patients with Itai-itai disease, the most severe form of chronic Cd intoxication. In order to prove that the anemia observed in chronic Cd intoxication arises from low production of EPO in the kidneys following the renal injury, we administered Cd to rats for a long period and performed the analysis of EPO mRNA inducibility in the kidneys. The rats administered Cd for 6 and 9 months showed anemia with low levels of plasma EPO as well as biochemical and histological renal tubular damage, and also hypoinduction of EPO mRNA in the kidneys. The results indicate that chronic Cd intoxication causes anemia by disturbing the EPO-production capacity of renal cells. (orig.). With 4 figs., 4 tabs.

  5. Inducing Herd Immunity against Seasonal Influenza in Long-Term Care Facilities through Employee Vaccination Coverage: A Transmission Dynamics Model

    Directory of Open Access Journals (Sweden)

    Aaron M. Wendelboe

    2015-01-01

    Full Text Available Introduction. Vaccinating healthcare workers (HCWs in long-term care facilities (LTCFs may effectively induce herd immunity and protect residents against influenza-related morbidity and mortality. We used influenza surveillance data from all LTCFs in New Mexico to validate a transmission dynamics model developed to investigate herd immunity induction. Material and Methods. We adjusted a previously published transmission dynamics model and used surveillance data from an active system among 76 LTCFs in New Mexico during 2006-2007 for model validation. We used a deterministic compartmental model with a stochastic component for transmission between residents and HCWs in each facility in order to simulate the random variation expected in such populations. Results. When outbreaks were defined as a dichotomous variable, our model predicted that herd immunity could be induced. When defined as an attack rate, the model demonstrated a curvilinear trend, but insufficiently strong to induce herd immunity. The model was sensitive to changes in the contact parameter β but was robust to changes in the visitor contact probability. Conclusions. These results further elucidate previous studies’ findings that herd immunity may not be induced by vaccinating HCWs in LTCFs; however, increased influenza vaccination coverage among HCWs reduces the probability of influenza infection among residents.

  6. Lead (Pb+2) impairs long-term memory and blocks learning-induced increases in hippocampal protein kinase C activity

    International Nuclear Information System (INIS)

    The long-term storage of information in the brain known as long-term memory (LTM) depends on a variety of intracellular signaling cascades utilizing calcium (Ca2+) and cyclic adenosine monophosphate as second messengers. In particular, Ca+2/phospholipid-dependent protein kinase C (PKC) activity has been proposed to be necessary for the transition from short-term memory to LTM. Because the neurobehavioral toxicity of lead (Pb+2) has been associated to its interference with normal Ca+2 signaling in neurons, we studied its effects on spatial learning and memory using a hippocampal-dependent discrimination task. Adult rats received microinfusions of either Na+ or Pb+2 acetate in the CA1 hippocampal subregion before each one of four training sessions. A retention test was given 7 days later to examine LTM. Results suggest that intrahippocampal Pb+2 did not affect learning of the task, but significantly impaired retention. The effects of Pb+2 selectively impaired reference memory measured in the retention test, but had no effect on the general performance because it did not affect the latency to complete the task during the test. Finally, we examined the effects of Pb+2 on the induction of hippocampal Ca+2/phospholipid-dependent PKC activity during acquisition training. The results showed that Pb+2 interfered with the learning-induced activation of Ca+2/phospholipid-dependent PKC on day 3 of acquisition. Overall, our results indicate that Pb+2 causes cognitive impairments in adult rats and that such effects might be subserved by interference with Ca+2-related signaling mechanisms required for normal LTM

  7. Long-Term (3 Years) Prognosis of Contrast-Induced Acute Kidney Injury After Coronary Angiography.

    Science.gov (United States)

    Pesarini, Gabriele; Lunardi, Mattia; Ederle, Francesco; Zivelonghi, Carlo; Scarsini, Roberto; Gambaro, Alessia; Lupo, Antonio; Vassanelli, Corrado; Ribichini, Flavio

    2016-06-01

    Contrast-induced acute kidney injury (CI-AKI) after coronary angiography or interventions is relatively frequent and portends adverse outcomes. The lack of a "universally accepted" definition, however, limits the integration and comparison of available data. We aimed to detect the CI-AKI definition that best correlates with the occurrence of clinical events at long-term in a 3-year follow-up study of patients at intermediate-to-high risk for CI-AKI. Furthermore, we sought to describe the incidence and long-term evolution of persistent renal damage (PRD) after CI-AKI and clarify the role of early (SCr) in CI-AKI prediction. Among a total of 216 patients enrolled at our center and followed for a median of 37 months, CI-AKI was diagnosed in 18.1% of cases (SCr increment ≥25% of baseline), 7.4% (SCr increment ≥0.5 mg/dl), and in 17.1% (SCr increment ≥0.3 mg/dl), according to 3 different definitions. The third definition was the only one significantly associated with the occurrence of events at 3 years (Cox regression, p = 0.04). PRD at 30 days, as detected by the same cutoff, significantly and independently identified patients at risk of worst outcomes at 3 years (p = 0.04 at multivariate Cox regression). Furthermore, a slight 5% to 10% increment of SCr compared with baseline, occurring as early as 12 hours postprocedure, was confirmed as a strong predictor of inhospital CI-AKI occurrence. In conclusion, an absolute increase in SCr ≥0.3 mg/dl seems to be most clinically informative cutoff for CI-AKI and PRD detection. PMID:27085934

  8. Targeting apoptosis to induce stable mixed hematopoietic chimerism and long-term allograft survival without myelosuppressive conditioning in mice.

    Science.gov (United States)

    Cippà, Pietro E; Gabriel, Sarah S; Chen, Jin; Bardwell, Philip D; Bushell, Andrew; Guimezanes, Annick; Kraus, Anna K; Wekerle, Thomas; Wüthrich, Rudolf P; Fehr, Thomas

    2013-08-29

    Induction of mixed hematopoietic chimerism results in donor-specific immunological tolerance by apoptosis-mediated deletion of donor-reactive lymphocytes. A broad clinical application of this approach is currently hampered by limited predictability and toxicity of the available conditioning protocols. We developed a new therapeutic approach to induce mixed chimerism and tolerance by a direct pharmacological modulation of the intrinsic apoptosis pathway in peripheral T cells. The proapoptotic small-molecule Bcl-2 inhibitor ABT-737 promoted mixed chimerism induction and reversed the antitolerogenic effect of calcineurin inhibitors by boosting the critical role of the proapoptotic Bcl-2 factor Bim. A short conditioning protocol with ABT-737 in combination with costimulation blockade and low-dose cyclosporine A resulted in a complete deletion of peripheral donor-reactive lymphocytes and was sufficient to induce mixed chimerism and robust systemic tolerance across full major histocompatibility complex barriers, without myelosuppression and by using moderate doses of bone marrow cells. Thus, immunological tolerance can be achieved by direct modulation of the intrinsic apoptosis pathway in peripheral lymphocytes-a new approach to translate immunological tolerance into clinically applicable protocols. PMID:23869083

  9. Effect of ascorbic acid on long-term cold exposure induced changes in thyroid activity in sprague dawley rats

    International Nuclear Information System (INIS)

    Objective: To determine the effect of ascorbic acid supplementation on long-term cold exposure induced changes in thyroid activity in Sprague-Dawley rats. Study Design: Experimental study. Place and Duration of Study: Physiology Department of Islamic International Medical College, Rawalpindi, National Institute of Health, Islamabad and Railway Hospital, Rawalpindi, from January to December 2009. Methodology: Ninety Sprague-Dawley rats were randomly divided into three groups of control, cold exposed and cold exposed along with ascorbic acid supplementation. After one month, their thyroid levels were analyzed by using chemiluminescent immunometric Assay on Siemens Immulite 2000 Analyzer. Results: After 4 weeks of cold exposure to experimental animals, the thyroid activity was raised significantly in the cold exposed group as compared to the control group (p-value for T3 difference = 0.004, T4 difference = 0.002 and TSH difference < 0.001). Supplementation with ascorbic acid in the third group normalized the thyroid hormone activity with p-value for difference in levels of T3 being 0.6661, T4 = 0.027 and TSH = 0.0028. Conclusion: Ascorbic acid prevented the cold induced changes in thyroid hormone levels in rodents. (author)

  10. DCP-LA neutralizes mutant amyloid beta peptide-induced impairment of long-term potentiation and spatial learning.

    Science.gov (United States)

    Nagata, Tetsu; Tomiyama, Takami; Tominaga, Takemi; Mori, Hiroshi; Yaguchi, Takahiro; Nishizaki, Tomoyuki

    2010-01-01

    Long-term potentiation (LTP) was monitored from the CA1 region of the intact rat hippocampus by delivering high frequency stimulation (HFS) to the Schaffer collateral commissural pathway. Intraventricular injection with mutant amyloid beta(1-42) peptide lacking glutamate-22 (Abeta(1-42)E22Delta), favoring oligomerization, 10 min prior to HFS, inhibited expression of LTP, with the potency more than wild-type amyloid beta(1-42) peptide. Intraperitoneal injection with the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) 70 min prior to HFS neutralized mutant Abeta(1-42)E22Delta peptide-induced LTP inhibition. In the water maze test, continuous intraventricular injection with mutant Abeta(1-42)E22Delta peptide for 14 days prolonged the acquisition latency as compared with that for control, with the potency similar to wild-type Abeta(1-42) peptide, and intraperitoneal injection with DCP-LA shortened the prolonged latency to control levels. The results of the present study indicate that DCP-LA neutralizes mutant Abeta(1-42)E22Delta peptide-induced impairment of LTP and spatial learning. PMID:19716848

  11. A plant 35S CaMV promoter induces long-term expression of luciferase in Atlantic salmon.

    Science.gov (United States)

    Seternes, Tore; Tonheim, Tom C; Myhr, Anne I; Dalmo, Roy A

    2016-01-01

    The long-term persistence and activity of a naked plasmid DNA (pGL3-35S) containing a luc gene (reporter gene) controlled by a plant 35S CaMV promoter was studied in Atlantic salmon (Salmo salar L.) after injection. Atlantic salmon (mean weight 70 grams) were injected intramuscularly with 100 μg of plasmid DNA. Blood, different tissues and organs were sampled at different time points up to day 535 after injection. Southern blot analysis suggested the presence of extra-chromosomally open circular, linear and supercoiled topoforms of pGL3-35S at day 150 after injection. At day 536 open circular and supercoiled topoforms were detected. Luciferase activity was detected at the injection site up to 536 days post-injection of pGL3-35S, where it peaked at day 150 and decreased to approximately 17% of its maximum activity by day 536. Our study demonstrated that a plasmid containing the 35S promoter was able to induce expression of a reporter gene/protein in fish in vivo and that the plasmid DNA persisted for a prolonged time after intramuscular injection. PMID:27114167

  12. Influence of minerals on lead-induced alterations in liver function in rats exposed to long-term lead exposure

    International Nuclear Information System (INIS)

    The objective of this study was to evaluate the role of minerals on lead-induced effect on the liver. Differentiation of minerals and heavy metals pose an inherent problem due to certain common properties shared by them. With this approach to the problem of heavy metal toxicity, in the present study two groups of male Wistar albino rats, one group (well-nourished) fed on mineral rich diet and other group (undernourished) fed on diet without mineral supplements were used. Both the groups of rats were subjected to long-term lead exposure. The diet of well-nourished group was supplemented with calcium (Ca); 1.2%, phosphorous (P); 0.6%, iron (Fe); 90 mg/kg, zinc (Zn); 50 mg/kg, magnesium (Mg); 0.08%, manganese (Mn); 70 mg/kg, selenium (Se); 0.2 mg/kg, copper (Cu); 5 mg/kg, molybdenum (Mo); 0.8 mg/kg, iodine (I); 0.6 mg/kg, cobalt (Co); 3.0 mg/kg. Their blood lead and parameters of liver function were monitored periodically. Results of the study showed a very high statistically significant increase (p < 0.001) in the blood lead (PbB) levels and liver function test parameters in the undernourished subjects compared to the well-nourished subjects. Nutritional management of lead poisoning is of importance since essential elements and toxic heavy metals may interact to minimize the absorption of lead.

  13. Long-term Follow-up of a Case of Gold Shunt Surgery for Refractory Silicone Oil–induced Glaucoma

    Science.gov (United States)

    Le, Ryan; Berger, Alan R.

    2016-01-01

    Purpose: To report the first case of gold shunt surgery for treatment of silicone oil–induced refractory glaucoma in a tertiary care academic center, with 5-year follow-up. Design: The study design is a case report. Participants: The participant was a patient who underwent gold shunt surgery. Methods: Institutional Research Ethics Board approval for the study was obtained. A diabetic patient was referred for refractory glaucoma with a history of proliferative diabetic retinal detachment, and surgery with silicone oil. She was uncontrolled on maximal medical therapy and following informed consent, gold shunt surgery was performed. Ocular outcomes and number of medications were reviewed over a 5-year period. Results: Following uncomplicated surgery, intraocular pressure was reduced from 41 to 14 mm Hg, and the number of medications was reduced from 4 to 1. Glaucomatous optic neuropathy remained stable. Conclusions: Gold shunt surgery in this challenging case of silicone oil refractory glaucoma provided long-term intraocular pressure control and reduced need for medication over a 5-year period. PMID:27253968

  14. Matrix metalloproteinases regulate the formation of dendritic spine head protrusions during chemically induced long-term potentiation.

    Directory of Open Access Journals (Sweden)

    Zsuzsanna Szepesi

    Full Text Available Dendritic spines are are small membranous protrusions that extend from neuronal dendrites and harbor the majority of excitatory synapses. Increasing evidence has shown that matrix metalloproteinases (MMPs, a family of extracellularly acting and Zn(2+-dependent endopeptidases, are able to rapidly modulate dendritic spine morphology. Spine head protrusions (SHPs are filopodia-like processes that extend from the dendritic spine head, representing a form of postsynaptic structural remodeling in response to altered neuronal activity. Herein, we show that chemically induced long-term potentiation (cLTP in dissociated hippocampal cultures upregulates MMP-9 activity that controls the formation of SHPs. Blocking of MMPs activity or microtubule dynamics abolishes the emergence of SHPs. In addition, autoactive recombinant MMP-9, promotes the formation of SHPs in organotypic hippocampal slices. Furthermore, spines with SHPs gained postsynaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA receptors upon cLTP and the synaptic delivery of AMPA receptors was controlled by MMPs. The present results strongly imply that MMP-9 is functionally involved in the formation of SHPs and the control of postsynaptic receptor distribution upon cLTP.

  15. Repeated Neonatal Propofol Administration Induces Sex-Dependent Long-Term Impairments on Spatial and Recognition Memory in Rats

    OpenAIRE

    Gonzales, Edson Luck T.; Yang, Sung Min; Choi, Chang Soon; Mabunga, Darine Froy N.; Kim, Hee Jin; Cheong, Jae Hoon; Ryu, Jong Hoon; Koo, Bon-Nyeo; Shin, Chan Young

    2015-01-01

    Propofol is an anesthetic agent that gained wide use because of its fast induction of anesthesia and rapid recovery post-anesthesia. However, previous studies have reported immediate neurodegeneration and long-term impairment in spatial learning and memory from repeated neonatal propofol administration in animals. Yet, none of those studies has explored the sex-specific long-term physical changes and behavioral alterations such as social (sociability and social preference), emotional (anxiety...

  16. Dynamic long-term microstructural and ultrastructural alterations in sensory nerves of rats of paclitaxel-induced neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    Wu Yuan; Li Jun; Zhou Junfei; Feng Yi

    2014-01-01

    Background Paclitaxel,as a first line anti-neoplastic compound,frequently produces long-term pain after tumors have been treated.Clinical manifestations are varied and non-specific.Pathology of the nervous system during the development of the neuropathic pain is unclear.Thus,eady diagnosis and treatment is often unsatisfying for patients.This study aimed to promote considerate understanding of the structural alteration of sensory nerves.Methods All rats were simply randomized into 3 groups:paclitaxel group,vehicle group and saline group.An established rat model of paclitaxel-induced peripheral neuropathy (2 mg/kg) was chosen for our research,behavior tests were operated during the procedure of 56 days.All rats were sampled on days 0,3,7,28 and 56.The hind paw plantar skin,sciatic nerves,dorsal root ganglion and attached fibers,and lumbar spinal cord were processed for light and electron microscopy.The differences among 3 groups were analyzed with one-way analysis of vadance (ANOVA).Results We affirmed that paclitaxel-induced mechano-aliodynia and mechano-hyperalgesia occured after a 3-7-day delay,and this pain peaked at day 28 and persisted to day 56.Paclitaxel and vehicle treatment both evoked thermalhyperalgesia.Paclitaxel-induced axonal and myelin sheath degeneration was evident.At days 3 and 7,significant increases in atypical mitochondria in both myelinated axons and C-fibers of paclitaxel-treated nerves indicated that injured mitochondria correlated to specific paclitaxel-induced neuropathic pain,and the abnormity sustained till day 56.Microtubule was unaffected in myelinated axons or C-fibers in paclitaxel-or vehicle-treated rats.Significant increase of G ratio was evident with paclitaxel injection at days 7 and 28.Conclusion Our research suggests a causal role for axonal degeneration,abnormalities in axonal mitochondria,and structural modification of axonal microtubules in paclitaxel-induced neuropathic pain,and the abnormal mitochondria could be connected

  17. Experiments of dike-induced deformation: Insights on the long-term evolution of divergent plate boundaries

    Science.gov (United States)

    Trippanera, D.; Ruch, J.; Acocella, V.; Rivalta, E.

    2015-10-01

    The shallow transport of magma occurs through dikes causing surface deformation. Our understanding of the effects of diking at the surface is limited, especially on the long term, for repeated intrusive episodes. We use analogue models to study the upper crustal deformation induced by dikes. We insert metal plates within cohesive sand with three setups: in setup A, the intrusion rises upward with constant thickness and in setups B and C, the intrusion thickens at a fixed depth, with final rectangular (setup B) or triangular (setup C) shape in section. Setup A creates a doming delimited by reverse faults, with secondary apical graben, without close correspondence in nature. In setups B and C, a depression flanked by two uplifted areas is bordered by inward dipping normal faults propagating downward and, for deeper intrusions in setup B, also by inner faults, reverse at the surface; this deformation is similar to what is observed in nature, suggesting a consistent physical behavior. Dikes in nature initially propagate developing a mode I fracture at the tip, subsequently thickened by magma intrusion, without any host rock translation in the propagation direction (as in setup A). The deformation pattern in setups B and C depends on the intrusion depth and thickness, consistently to what is observed along divergent plate boundaries. The early deformation in setups B and C is similar to that from a single rifting episode (i.e., Lakagigar, Iceland, and Dabbahu, Afar), whereas the late stages resemble the structure of mature rifts (i.e., Krafla, Iceland), confirming diking as a major process in shaping divergent plate boundaries.

  18. Long-Term Effects of (-)-Epigallocatechin Gallate (EGCG) on Pristane-Induced Arthritis (PIA) in Female Dark Agouti Rats.

    Science.gov (United States)

    Leichsenring, Anna; Bäcker, Ingo; Furtmüller, Paul G; Obinger, Christian; Lange, Franziska; Flemmig, Jörg

    2016-01-01

    Rheumatoid arthritis (RA)-a widespread chronic inflammatory disease in industrialized countries-is characterized by a persistent and progressive joint destruction. The chronic pro-inflammatory state results from a mutual activation of the innate and the adaptive immune system, while the exact pathogenesis mechanism is still under discussion. New data suggest a role of the innate immune system and especially polymorphonuclear granulocytes (PMNs, neutrophils) not only during onset and the destructive phase of RA but also at the chronification of the disease. Thereby the enzymatic activity of myeloperoxidase (MPO), a peroxidase strongly abundant in neutrophils, may be important: While its peroxidase activity is known to contribute to cartilage destruction at later stages of RA the almost MPO-specific oxidant hypochlorous acid (HOCl) is also discussed for certain anti-inflammatory effects. In this study we used pristane-induced arthritis (PIA) in Dark Agouti rats as a model for the chronic course of RA in man. We were able to shown that a specific detection of the HOCl-producing MPO activity provides a sensitive new marker to evaluate the actual systemic inflammatory status which is only partially detectable by the evaluation of clinical symptoms (joint swelling and redness measurements). Moreover, we evaluated the long-term pharmacological effect of the well-known anti-inflammatory flavonoid epigallocatechin gallate (EGCG). Thereby only upon early and continuous oral application of this polyphenol the arthritic symptoms were considerably diminished both in the acute and in the chronic phase of the disease. The obtained results were comparable to the treatment control (application of methotrexate, MTX). As revealed by stopped-flow kinetic measurements, EGCG may regenerate the HOCl-production of MPO which is known to be impaired at chronic inflammatory diseases like RA. It can be speculated that this MPO activity-promoting effect of EGCG may contribute to the

  19. Experiments of dike-induced deformation: Insights on the long-term evolution of divergent plate boundaries

    KAUST Repository

    Trippanera, D.

    2015-10-22

    The shallow transport of magma occurs through dikes causing surface deformation. Our understanding of the effects of diking at the surface is limited, especially on the long term, for repeated intrusive episodes. We use analogue models to study the upper crustal deformation induced by dikes. We insert metal plates within cohesive sand with three setups: in setup A, the intrusion rises upward with constant thickness and in setups B and C, the intrusion thickens at a fixed depth, with final rectangular (setup B) or triangular (setup C) shape in section. Setup A creates a doming delimited by reverse faults, with secondary apical graben, without close correspondence in nature. In setups B and C, a depression flanked by two uplifted areas is bordered by inward dipping normal faults propagating downward and, for deeper intrusions in setup B, also by inner faults, reverse at the surface; this deformation is similar to what is observed in nature, suggesting a consistent physical behavior. Dikes in nature initially propagate developing a mode I fracture at the tip, subsequently thickened by magma intrusion, without any host rock translation in the propagation direction (as in setup A). The deformation pattern in setups B and C depends on the intrusion depth and thickness, consistently to what is observed along divergent plate boundaries. The early deformation in setups B and C is similar to that from a single rifting episode (i.e., Lakagigar, Iceland, and Dabbahu, Afar), whereas the late stages resemble the structure of mature rifts (i.e., Krafla, Iceland), confirming diking as a major process in shaping divergent plate boundaries.

  20. Short-term and long-term clinostat and vibration-induced biochemical changes in dwarf Marigold stems

    Science.gov (United States)

    Siegel, S. M.; Siegel, B. Z.

    Stems of 21-day dwarf Marigold plants cultivated on the clinostat were compared with plants cultivated on vertical axis rotators (``vibrational controls'') and stationary controls for long-term changes in cell wall composition. Stems of 21-day plants grown under stationary conditions and subsequently exposed to the clinostat for 24 hours were also analyzed. Among the long-term markers, calcium, lignin, and protein-bound hemicellulose (possibly cell wall glycoprotein) clearly differentiated the effects of vibration from those of the clinostat. Short-term differential responses included rate of ethylene production, nastic movement and peroxidase activity of the cell wall, but not of the protoplast.

  1. Evidence from a rare case-study for Hebbian-like changes in structural connectivity induced by long-term deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Tim J Van Hartevelt

    2015-06-01

    Full Text Available It is unclear whether Hebbian-like learning occurs at the level of long-range white matter connections in humans, i.e. where measurable changes in structural connectivity are correlated with changes in functional connectivity. However, the behavioral changes observed after deep brain stimulation (DBS suggest the existence of such Hebbian-like mechanisms occurring at the structural level with functional consequences. In this rare case study, we obtained the full network of white matter connections of one patient with Parkinson's disease before and after long-term DBS and combined it with a computational model of ongoing activity to investigate the effects of DBS-induced long-term structural changes. The results show that the long-term effects of DBS on resting-state functional connectivity is best obtained in the computational model by changing the structural weights from the subthalamic nucleus to the putamen and the thalamus in a Hebbian-like manner. Moreover, long-term DBS also significantly changed the structural connectivity towards normality in terms of model-based measures of segregation and integration of information processing, two key concepts of brain organization. This novel approach using computational models to model the effects of Hebbian-like changes in structural connectivity allowed us to causally identify the possible underlying neural mechanisms of long-term DBS using rare case study data. In time, this could help predict the efficacy of individual DBS targeting and identify novel DBS targets.

  2. Long-term niacin treatment induces insulin resistance and adrenergic responsiveness in adipocytes by adaptive downregulation of phosphodiesterase 3B

    NARCIS (Netherlands)

    Heemskerk, M.M.; Berg, S.A. van den; Pronk, A.C.M.; Klinken, J.B. van; Boon, M.R.; Havekes, L.M.; Rensen, P.C.N.; Willems van Dijk, K.; Harmelen, V. van

    2014-01-01

    The lipid-lowering effect of niacin has been attributed to the inhibition of cAMP production in adipocytes, thereby inhibiting intracellular lipolysis and release of nonesterified fatty acids (NEFA) to the circulation. However, long-term niacin treatment leads to a normalization of plasma NEFA level

  3. Shear-induced Fracture Slip and Permeability Change. Implications for Long-term Performance of a Deep Geological Repository

    International Nuclear Information System (INIS)

    second part of the study stress paths obtained from the thermo-mechanical analysis were used as boundary conditions in DFN-DEM analysis of six DFN models at the repository level. Increases of permeability up to a factor of four were observed during thermal loading history and shear dilation of fractures was not recovered after cooling of the repository. An understanding of the stress path and potential areas of slip induced shear dilation and related permeability changes during the lifetime of a repository for spent nuclear fuel is of utmost importance for analysing long-term safety. The result of this study will assist in identifying critical areas around a repository where fracture shear slip is likely to develop. The present study is restricted to rock mass conditions found at repository level in SKB's Forsmark site

  4. Long-term collections

    CERN Multimedia

    Collectes à long terme

    2007-01-01

    The Committee of the Long Term Collections (CLT) asks for your attention for the following message from a young Peruvian scientist, following the earthquake which devastated part of her country a month ago.

  5. Ionizing radiation-induced long-term expression of senescence markers in mice is independent of p53 and immune status

    OpenAIRE

    Le, Oanh; Rodier, Francis; Fontaine, Francois; Coppe, Jean-Philippe; Campisi, Judith; DeGregori, James; Laverdiére, Caroline; Kokta, Victor; Haddad, Elie; Beauséjour, Christian M

    2010-01-01

    Exposure to IR has been shown to induce the formation of senescence markers, a phenotype that coincides with life-long delayed repair and regeneration of irradiated tissues. We hypothesised that IR-induced senescence markers could persist long-term in vivo, possibly contributing to the permanent reduction in tissue functionality. Here we show that mouse tissues exposed to a sublethal dose of IR display persistent (up to 45 weeks, the maximum time analysed) DNA damage foci and increased p16INK...

  6. Temperature induced decoupling of enzymatic hydrolysis and carbon remineralization in long-term incubations of Arctic and temperate sediments

    OpenAIRE

    Robador, Alberto; Brüchert, Volker; Steen, Andrew; Arnosti, Carol

    2010-01-01

    Udgivelsesdato: 2010 Extracellular enzymatic hydrolysis of high-molecular weight organic matter is the initial step in sedimentary organic carbon degradation and is often regarded as the rate-limiting step. Temperature effects on enzyme activities may therefore exert an indirect control on carbon mineralization. We explored the temperature sensitivity of enzymatic hydrolysis and its connection to subsequent steps in anoxic organic carbon degradation in long-term incubations of sediments fr...

  7. Using corporate governance to enhance 'long-term situation awareness' and assist in the avoidance of organisation-induced disasters.

    Science.gov (United States)

    Siemieniuch, C E; Sinclair, M A

    2008-03-01

    This paper considers the issue of how corporate governance can and should deal with the long-term understanding of systems health-what we may call 'long-term situation awareness' (i.e. which evolves and is coherent over time) for organisational systems (and their component sub systems) in the engineering domain. Many characteristics affect long-term situation awareness-the rate of change to processes, pressures for greater efficiency from existing resources, changes in personnel, cultural changes and changes to the operational environment of the organisational systems. Many disasters (e.g. Chernobyl, Flixborough, Piper Alpha) have a causal path that indicates a loss of group situation awareness, over a long period of time. The problem of the gradual, slow drift over many years towards unsafe conduct of company operations is discussed and examples of possible consequences provided. A 'parable' from the world of manufacturing is used to exemplify the problem. The paper goes on to discuss some ways by which this problem could be addressed and longer-term system situational awareness increased; essentially by good corporate governance, knowledge management and ownership of processes. Links are made to the literature on these topics, and a route map to help organisations to gain the benefits is offered. PMID:17624296

  8. Long-term blood pressure changes induced by the 2009 L'Aquila earthquake: assessment by 24 h ambulatory monitoring.

    Science.gov (United States)

    Giorgini, Paolo; Striuli, Rinaldo; Petrarca, Marco; Petrazzi, Luisa; Pasqualetti, Paolo; Properzi, Giuliana; Desideri, Giovambattista; Omboni, Stefano; Parati, Gianfranco; Ferri, Claudio

    2013-09-01

    An increased rate of cardiovascular and cerebrovascular events has been described during and immediately after earthquakes. In this regard, few data are available on long-term blood pressure control in hypertensive outpatients after an earthquake. We evaluated the long-term effects of the April 2009 L'Aquila earthquake on blood pressure levels, as detected by 24 h ambulatory blood pressure monitoring. Before/after (mean±s.d. 6.9±4.5/14.2±5.1 months, respectively) the earthquake, the available 24 h ambulatory blood pressure monitoring data for the same patients were extracted from our database. Quake-related daily life discomforts were evaluated through interviews. We enrolled 47 patients (25 female, age 52±14 years), divided into three groups according to antihypertensive therapy changes after versus before the earthquake: unchanged therapy (n=24), increased therapy (n=17) and reduced therapy (n=6). Compared with before the quake, in the unchanged therapy group marked increases in 24 h (P=0.004), daytime (P=0.01) and nighttime (P=0.02) systolic blood pressure were observed after the quake. Corresponding changes in 24 h (P=0.005), daytime (P=0.01) and nighttime (P=0.009) diastolic blood pressure were observed. Daily life discomforts were reported more frequently in the unchanged therapy and increased therapy groups than the reduced therapy group (P=0.025 and P=0.018, respectively). In conclusion, this study shows that patients with unchanged therapy display marked blood pressure increments up to more than 1 year after an earthquake, as well as long-term quake-related discomfort. Our data suggest that particular attention to blood pressure levels and adequate therapy modifications should be considered after an earthquake, not only early after the event but also months later. PMID:23595046

  9. Long-term in vivo polychlorinated biphenyl 126 exposure induces oxidative stress and alters proteomic profile on islets of Langerhans

    OpenAIRE

    Loiola, Rodrigo Azevedo; dos Anjos, Fabyana Maria; Shimada, Ana Lúcia; Cruz, Wesley Soares; Drewes, Carine Cristiane; Rodrigues, Stephen Fernandes; Cardozo, Karina Helena Morais; Carvalho, Valdemir Melechco; Pinto, Ernani; Farsky, Sandra Helena

    2016-01-01

    It has been recently proposed that exposure to polychlorinated biphenyls (PCBs) is a risk factor to type 2 diabetes mellitus (DM2). We investigated this hypothesis using long-term in vivo PCB126 exposure to rats addressing metabolic, cellular and proteomic parameters. Male Wistar rats were exposed to PCB126 (0.1, 1 or 10 μg/kg of body weight/day; for 15 days) or vehicle by intranasal instillation. Systemic alterations were quantified by body weight, insulin and glucose tolerance, and blood bi...

  10. Evaluation of Bronchiolar and Alveolar Cell Injuries Induced by Short- and Long-term Exposure to Sidestream Smoke

    OpenAIRE

    Kwon, Kun-Young; Jung, Hye-Ra; Hwang, Ilseon; Choi, Won-Il

    2012-01-01

    Background We investigated effects of short- and long-term exposure to sidestream smoke on the bronchiolar and alveolar cells in Sprague-Dawley rats. Methods Rats were divided into five experimental groups: groups 1, 2, and 3 (1-month exposure to 3, 5, and 7 cigarettes a day, respectively), groups 4 and 5 (3- and 6 month exposure to five cigarettes a day, respectively). We examined the morphologic changes, the expressions of tumor necrosis factor α (TNF-α), tumor growth factor β1 (TGF-β1), in...

  11. Glycine induces a novel form of long-term potentiation in the superficial layers of the superior colliculus

    OpenAIRE

    Platt, Bettina; Bate, Joanne R; von Linstow Roloff, Eva; Withington, Deborah J

    1998-01-01

    The mammalian superior colliculus (SC) is a midbrain nucleus containing space maps of different sensory modalities which show various forms of age- and activity-dependent plasticity in vivo and in vitro. In the present study, we aimed to characterize the role of glycine (Gly) receptors in the SC, and we observed that application of glycine (Gly; 500 μM and 3 mM) for 7 min to SC slices of adult guinea-pigs caused a novel form of long-term potentiation (termed LTPgly) of evoked excitatory posts...

  12. Effect of Korean red ginseng extract on liver damage induced by short-term and long-term ethanol treatment in rats

    OpenAIRE

    Seo, Su-Jeong; Cho, Jae Youl; Jeong, Yeon Ho; Choi, Yong-Soon

    2013-01-01

    Korean red ginseng (KRG) is prepared by the process of steaming the roots of Panax ginseng. In this study, the feeding effects of KRG-water extract (KRGE) on ethanol-induced liver damage were elucidated by measuring serum biomarkers in rats. Serum γ-glutamyltranspeptidase (γ-GT) activity and the concentration of malondialdehyde (MDA) were significantly increased by short-term and long-term ethanol treatment in rats, whereas the activities of serum glutamate pyruvate transaminase (GPT) and glu...

  13. Association between arthritis score at the onset of the disease and long-term locomotor outcome in adjuvant-induced arthritis in rats

    OpenAIRE

    Mossiat, Claude; Laroche, Davy; Prati, Clément; Pozzo, Thierry; Demougeot, Céline; Marie, Christine

    2015-01-01

    Introduction To investigate the connection between the intensity of initial symptoms of inflammation and locomotor outcome in rheumatoid arthritis, we examined the relationship between long-term locomotor abnormalities and signs of inflammation at the onset of the disease in adjuvant-induced arthritis (AIA) in rats. Methods The arthritis score and hind-paw diameter were followed from immunization to day 195 (~7 months). At this time, locomotion was recorded during forced treadmill walking usi...

  14. Long-Term Collections

    CERN Multimedia

    Comité des collectes à long terme

    2011-01-01

    It is the time of the year when our fireman colleagues go around the laboratory for their traditional calendars sale. A part of the money of the sales will be donated in favour of the long-term collections. We hope that you will welcome them warmly.

  15. Long term morphological modelling

    DEFF Research Database (Denmark)

    Kristensen, Sten Esbjørn; Deigaard, Rolf; Taaning, Martin;

    2010-01-01

    A morphological modelling concept for long term nearshore morphology is proposed and examples of its application are presented and discussed. The model concept combines parameterised representations of the cross-shore morphology, with a 2DH area model for waves, currents and sediment transport in...

  16. Long-term Smoking Mediated Down-regulation of Smad3 Induces Resistance to Carboplatin in Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Debangshu Samanta

    2012-07-01

    Full Text Available While numerous cell signaling pathways are known to play decisive roles in chemotherapeutic response, relatively little is known about the impact of the Smad-dependent transforming growth factor β pathway on the therapeutic outcome. Previous reports suggested that patients with lung cancer who continue to smoke while receiving chemotherapy have a poorer outcome than their nonsmoking counterparts do. In our previous study, we showed that long-term cigarette smoke condensate (CSC-mediated down-regulation of Smad3 induces tumorigenesis. The objective of this study was to determine the mechanism of function of Smad3 in chemoresistance induced by CSC in human lung cell lines, namely, A549 and HPL1A. Long-term CSC treatment increases the half-maximal inhibitory concentration (IC50 of carboplatin and makes cells resistant to carboplatin. The increase in IC50 of long-term CSC-treated cells is due to the reduced induction in apoptosis by carboplatin. The increase in IC50 and decrease in apoptosis in long-term CSC-treated cells is correlated with the expression of Bcl2. We have determined that Bcl2 is both necessary and sufficient to make the cells resistant to carboplatin. We have also shown that Smad3 acts upstream to regulate the expression of Bcl2 specifically and, thus, sensitivity of the cells to carboplatin. This is supported by the inverse correlation between the expressions of Smad3 and Bcl2 in human lung tumors. Collectively, these data suggest that loss of Smad3 expression in CSC-treated cells induces resistance to carboplatin by upregulating the expression of Bcl2. This study explains, at least in part, the higher chemoresistance rate observed in smokers.

  17. Antibody-induced neutrophil depletion prior to the onset of pneumococcal meningitis influences long-term neurological complications in mice.

    Science.gov (United States)

    Too, Lay Khoon; Mitchell, Andrew J; McGregor, Iain S; Hunt, Nicholas H

    2016-08-01

    During pneumococcal meningitis, clearance of bacteria by recruited neutrophils is crucial for host protection. However, these innate immune mechanisms are often insufficient and treatment with antibiotics is necessary to prevent death. Despite this antibiotic treatment, approximately half of all survivors suffer lifelong neurological problems. There is growing evidence indicating the harmful effects of neutrophils on CNS integrity. Therefore, the present study investigated the roles of neutrophils in the acute inflammatory response and the resulting long-term neuropsychological effects in murine pneumococcal meningitis. Long-term behavioural and cognitive functions in mice were measured using an automated IntelliCage system. Neutrophil depletion with antibody 1A8 as adjunctive therapy was shown to remarkably impair survival in meningitic C57BL/6J mice despite antibiotic (ceftriaxone) treatment. This was accompanied by increased bacterial load in the cerebrospinal fluid (CSF) and an increase in IL-1β, but decrease in TNF, within the CSF at 20h after bacterial inoculation. In the longer term, the surviving neutrophil-depleted post-meningitic (PM) mice displayed reduced diurnal hypolocomotion compared to PM mice treated with an isotype antibody. However, they showed nocturnal hyperactivity, and greater learning impairment in a patrolling task that is believed to depend upon an intact hippocampus. The data thus demonstrate two important mechanisms: 1. Neutrophil extravasation into the CNS during pneumococcal meningitis influences the pro-inflammatory response and is central to control of the bacterial load, an increase in which may lead to death. 2. Neutrophil-mediated changes in the acute inflammatory response modulate the neuropsychological sequelae in mice that survive pneumococcal meningitis. PMID:26965652

  18. Tumor vaccine composed of C-class CpG oligodeoxynucleotides and irradiated tumor cells induces long-term antitumor immunity

    Directory of Open Access Journals (Sweden)

    Cerkovnik Petra

    2010-09-01

    Full Text Available Abstract Background An ideal tumor vaccine should activate both effector and memory immune response against tumor-specific antigens. Beside the CD8+ T cells that play a central role in the generation of a protective immune response and of long-term memory, dendritic cells (DCs are important for the induction, coordination and regulation of the adaptive immune response. The DCs can conduct all of the elements of the immune orchestra and are therefore a fundamental target and tool for vaccination. The present study was aimed at assessing the ability of tumor vaccine composed of C-class CpG ODNs and irradiated melanoma tumor cells B16F1 followed by two additional injections of CpG ODNs to induce the generation of a functional long-term memory response in experimental tumor model in mice (i.p. B16F1. Results It has been shown that the functional memory response in vaccinated mice persists for at least 60 days after the last vaccination. Repeated vaccination also improves the survival of experimental animals compared to single vaccination, whereas the proportion of animals totally protected from the development of aggressive i.p. B16F1 tumors after vaccination repeated three times varies between 88.9%-100.0%. Additionally, the long-term immune memory and tumor protection is maintained over a prolonged period of time of at least 8 months. Finally, it has been demonstrated that following the vaccination the tumor-specific memory cells predominantly reside in bone marrow and peritoneal tissue and are in a more active state than their splenic counterparts. Conclusions In this study we demonstrated that tumor vaccine composed of C-class CpG ODNs and irradiated tumor cells followed by two additional injections of CpG ODNs induces a long-term immunity against aggressive B16F1 tumors.

  19. Long-term exposure to a magnetic field (5 mT at 60 Hz) increases X-ray-induced mutations

    International Nuclear Information System (INIS)

    Exposure to extremely low frequency magnetic field (ELFMF) at 400 mT has been shown to induce mutations (Mutat. Res., 349: 109-114, 1996; Int. J. Radiat. Biol., 71: 75-79, 1997; and Biochem. Biophys. Res. Commun., 243: 579-584, 1998). However, whether ELFMF at low flux densities (under 1 mT) induces mutations is debatable. We investigated the effect of long-term exposure to 5 mT ELFMF at 60 Hz on mutant frequency. Chinese hamster ovary K1 (CHO-K1) cells were exposed or sham-exposed to 5 mT ELFMF for up to 6 weeks with or without X-irradiation (3 Gy), and the mutant frequency of the hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene was analyzed. Long-term exposure to 5 mT ELFMF did not increase mutations, suggesting a threshold for mutation induction greater than 115 mA/m2 or a magnetic density of 5 mT. However, enhancement of the X-ray-induced mutation rate was observed after treatment with X-irradiation followed by long-term exposure to 5 mT ELFMF. At little as a 1-week exposure to ELFMF after X-irradiation enhanced the mutation rate. We also found that 400 mT exposure enhanced the mutation rate induced by X-irradiation (Mutat. Res., 349: 109-114, 1996). These results suggest that exposure to more than 5 mT ELFMF may promote X-ray-induced mutations. (author)

  20. Long-term functional duration of immune responses to HCV NS3/4A induced by DNA vaccination.

    Science.gov (United States)

    Ahlén, G; Holmström, F; Gibbs, A; Alheim, M; Frelin, L

    2014-08-01

    We have investigated the ability of hepatitis C virus non-structural (NS) 3/4A-DNA-based vaccines to activate long-term cell-mediated immune responses in mice. Wild-type and synthetic codon optimized (co) NS3/4A DNA vaccines have previously been shown to be immunogenic in mice, rabbits and humans, although we have very poor knowledge about the longevity of the immune responses primed. We therefore analyzed the functionality of primed NS3/4A-specific immune responses in BALB/c (H-2(d)) and/or C57BL/6J (H-2(b)) mice 1, 2, 3, 4, 6, 12 and 16 months after the last immunization. Mice were immunized one, two, three or four times using gene gun delivery to the skin or by intramuscular administration. Immunological responses after immunization were monitored by protection against in vivo challenge of NS3/4A-expressing syngeneic tumor cells. In addition, functionality of the NS3/4A-specific T cells was analyzed by a standard cytotoxicity assay. First, we identified a new unique murine H-2(d)-restricted NS3/4A cytotoxic T lymphocyte (CTL) epitope, which enabled us to study the epitope-specific immune responses. Our results show that the coNS3/4A vaccine was highly immunogenic by determination of interferon-γ/tumor necrosis factor-α production and lytic cytotoxic T cells, which could efficiently inhibit in vivo tumor growth. Importantly, we showed that one to four monthly immunizations protected mice from tumor development when challenged up to 16 months after the last immunization. When determining the functionality of NS3/4A-specific T cells in vitro, we showed detectable lytic activity up to 12 months after the last immunization. Thus, NS3/4A-based DNA vaccines activate potent cellular immune responses that are present and function in both BALB/c and C57BL/6J mice up to 12-16 months after the last immunization. The induction of long-term immunity after NS3/4A DNA immunization has not been shown previously and supports the use of NS3/4A in hepatitis C virus vaccine

  1. Depression is associated with some patient-perceived cosmetic changes, but not with radiotherapy-induced late toxicity, in long-term breast cancer survivors. : Depression-associated factors in long-term breast cancer survivors

    OpenAIRE

    Brunault, Paul; Suzanne, Isabelle; Trzepidur-Edom, Magdalena; Garaud, Pascal; Calais, Gilles; Toledano, Alain; Camus, Vincent

    2013-01-01

    OBJECTIVE: Although depression is prevalent in long-term breast cancer survivors (LTBCS; ≥5 years since diagnosis), it is underdiagnosed and undertreated. A better understanding of factors associated with depression could improve depression screening, treatment, and prevention in this population. Our study aimed to assess the link between patient and doctor ratings of breast cosmetic outcomes, late radiotherapy toxicity, and depression in LTBCS. METHODS: In all, 214 patients recruited from th...

  2. CD19 CAR-targeted T cells induce long-term remission and B Cell Aplasia in an immunocompetent mouse model of B cell acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Marco L Davila

    Full Text Available Although many adults with B cell acute lymphoblastic leukemia (B-ALL are induced into remission, most will relapse, underscoring the dire need for novel therapies for this disease. We developed murine CD19-specific chimeric antigen receptors (CARs and an immunocompetent mouse model of B-ALL that recapitulates the disease at genetic, cellular, and pathologic levels. Mouse T cells transduced with an all-murine CD3ζ/CD28-based CAR that is equivalent to the one being used in our clinical trials, eradicate B-ALL in mice and mediate long-term B cell aplasias. In this model, we find that increasing conditioning chemotherapy increases tumor eradication, B cell aplasia, and CAR-modified T cell persistence. Quantification of recipient B lineage cells allowed us to estimate an in vivo effector to endogenous target ratio for B cell aplasia maintenance. In mice exhibiting a dramatic B cell reduction we identified a small population of progenitor B cells in the bone marrow that may serve as a reservoir for long-term CAR-modified T cell stimulation. Lastly, we determine that infusion of CD8+ CAR-modified T cells alone is sufficient to maintain long-term B cell eradication. The mouse model we report here should prove valuable for investigating CAR-based and other therapies for adult B-ALL.

  3. Long-Term Training with a Brain-Machine Interface-Based Gait Protocol Induces Partial Neurological Recovery in Paraplegic Patients.

    Science.gov (United States)

    Donati, Ana R C; Shokur, Solaiman; Morya, Edgard; Campos, Debora S F; Moioli, Renan C; Gitti, Claudia M; Augusto, Patricia B; Tripodi, Sandra; Pires, Cristhiane G; Pereira, Gislaine A; Brasil, Fabricio L; Gallo, Simone; Lin, Anthony A; Takigami, Angelo K; Aratanha, Maria A; Joshi, Sanjay; Bleuler, Hannes; Cheng, Gordon; Rudolph, Alan; Nicolelis, Miguel A L

    2016-01-01

    Brain-machine interfaces (BMIs) provide a new assistive strategy aimed at restoring mobility in severely paralyzed patients. Yet, no study in animals or in human subjects has indicated that long-term BMI training could induce any type of clinical recovery. Eight chronic (3-13 years) spinal cord injury (SCI) paraplegics were subjected to long-term training (12 months) with a multi-stage BMI-based gait neurorehabilitation paradigm aimed at restoring locomotion. This paradigm combined intense immersive virtual reality training, enriched visual-tactile feedback, and walking with two EEG-controlled robotic actuators, including a custom-designed lower limb exoskeleton capable of delivering tactile feedback to subjects. Following 12 months of training with this paradigm, all eight patients experienced neurological improvements in somatic sensation (pain localization, fine/crude touch, and proprioceptive sensing) in multiple dermatomes. Patients also regained voluntary motor control in key muscles below the SCI level, as measured by EMGs, resulting in marked improvement in their walking index. As a result, 50% of these patients were upgraded to an incomplete paraplegia classification. Neurological recovery was paralleled by the reemergence of lower limb motor imagery at cortical level. We hypothesize that this unprecedented neurological recovery results from both cortical and spinal cord plasticity triggered by long-term BMI usage. PMID:27513629

  4. Adrenocortical and Adipose Responses to High-Altitude-Induced, Long-Term Hypoxia in the Ovine Fetus

    Directory of Open Access Journals (Sweden)

    Dean A. Myers

    2012-01-01

    Full Text Available By late gestation, the maturing hypothalamo-pituitary-adrenal (HPA axis aids the fetus in responding to stress. Hypoxia represents a significant threat to the fetus accompanying situations such as preeclampsia, smoking, high altitude, and preterm labor. We developed a model of high-altitude (3,820 m, long-term hypoxia (LTH in pregnant sheep. We describe the impact of LTH on the fetal HPA axis at the level of the hypothalamic paraventricular nucleus (PVN, anterior pituitary corticotrope, and adrenal cortex. At the PVN and anterior pituitary, the responses to LTH are consistent with hypoxia being a potent activator of the HPA axis and potentially maladaptive, while the adrenocortical response to LTH appears to be primarily adaptive. We discuss mechanisms involved in the delicate balance between these seemingly opposing responses that preserve the normal ontogenic rise in fetal plasma cortisol essential for organ maturation and in this species, birth. Further, we examine the response to, and ramifications of, an acute secondary stressor in the LTH fetus. We provide an integrative model on the potential role of adipose in modulating these responses to LTH. Integration of these adaptive responses to LTH plays a key role in promoting normal fetal growth and development under conditions of a chronic stress.

  5. Methamphetamine-induced enhancement of hippocampal long-term potentiation is modulated by NMDA and GABA receptors in the shell-accumbens.

    Science.gov (United States)

    Heysieattalab, Soomaayeh; Naghdi, Nasser; Hosseinmardi, Narges; Zarrindast, Mohammad-Reza; Haghparast, Abbas; Khoshbouei, Habibeh

    2016-08-01

    Addictive drugs modulate synaptic transmission in the meso-corticolimbic system by hijacking normal adaptive forms of experience-dependent synaptic plasticity. Psychostimulants such as METH have been shown to affect hippocampal synaptic plasticity, albeit with a less understood synaptic mechanism. METH is one of the most addictive drugs that elicit long-term alterations in the synaptic plasticity in brain areas involved in reinforcement learning and reward processing. Dopamine transporter (DAT) is one of the main targets of METH. As a substrate for DAT, METH decreases dopamine uptake and increases dopamine efflux via the transporter in the target brain regions such as nucleus accumbens (NAc) and hippocampus. Due to cross talk between NAc and hippocampus, stimulation of NAc has been shown to alter hippocampal plasticity. In this study, we tested the hypothesis that manipulation of glutamatergic and GABA-ergic systems in the shell-NAc modulates METH-induced enhancement of long term potentiation (LTP) in the hippocampus. Rats treated with METH (four injections of 5 mg/kg) exhibited enhanced LTP as compared to saline-treated animals. Intra-NAc infusion of muscimol (GABA receptor agonist) decreased METH-induced enhancement of dentate gyrus (DG)-LTP, while infusion of AP5 (NMDA receptor antagonist) prevented METH-induced enhancement of LTP. These data support the interpretation that reducing NAc activity can ameliorate METH-induced hippocampal LTP through a hippocampus-NAc-VTA circuit loop. Synapse 70:325-335, 2016. © 2016 Wiley Periodicals, Inc. PMID:27029021

  6. High level of Bcl-2 counteracts apoptosis mediated by a live rabies virus vaccine strain and induces long-term infection

    International Nuclear Information System (INIS)

    We report here that rabies virus strains, currently used to immunize wildlife against rabies, induce not only caspase-dependent apoptosis in the human lymphoblastoid Jurkat T cell line (Jurkat-vect), but also a caspase-independent pathway involving the apoptosis-inducing factor (AIF). In contrast, a strain of neurotropic RV that does not induce apoptosis did not activate caspases or induce AIF translocation. Bcl-2 overproduction in Jurkat T cells (Jurkat-Bcl-2) abolished both pathways. ERA infection and production were similar in Jurkat-vect and Jurkat-Bcl-2 cells, indicating Bcl-2 has no direct antiviral effects. Bcl-2 production is naturally upregulated by day 3 in ERA-infected Jurkat-vect cultures. The increase in Bcl-2 levels seems to be controlled by the virus infection itself and results in the establishment of long-term, persistently infected cultures that continue to produce virus. Thus, in infections with live RV vaccine strains, infected cells may be productive reservoirs of virus in the long term. This may account for the high efficacy of live rabies vaccines

  7. Neo-synthesis of estrogenic or androgenic neurosteroids determine whether long-term potentiation or depression is induced in hippocampus of male rat

    Directory of Open Access Journals (Sweden)

    Michela eDi Mauro

    2015-10-01

    Full Text Available Estrogenic and androgenic steroids synthesized in the brain may rapidly modulate synaptic plasticity interacting with specific membrane receptors. We explored by electrophysiological recordings in hippocampal slices of male rat the influence of 17b-estradiol (E2 and 5a-dihydrotestosterone (DHT neo-synthesis on the synaptic changes induced in the CA1 region. Induction of long-term depression (LTD and depotentiation (DP by low frequency stimulation (LFS, 15 min-1 Hz and of long-term potentiation (LTP by high (HFS, 1 s-100 Hz, medium (MFS, 1 s-50 Hz, or weak (WFS, 1 s-25 Hz frequency stimulation was assayed under inhibitors of enzymes converting testosterone (T into DHT (5a-reductase and T into E2 (P450-aromatase. We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved. Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2. For intermediate stimulation protocols DHT, but not E2 synthesis, was involved in the production of a small LTP induced by WFS, while the E2 synthesis was required for the MFS-dependent LTP. Under the combined block of DHT and E2 synthesis all stimulation frequencies induced partial LTP. Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects.

  8. Long-term electromagnetic pulse exposure induces Abeta deposition and cognitive dysfunction through oxidative stress and overexpression of APP and BACE1.

    Science.gov (United States)

    Jiang, Da-Peng; Li, Jin-Hui; Zhang, Jie; Xu, Sheng-Long; Kuang, Fang; Lang, Hai-Yang; Wang, Ya-Feng; An, Guang-Zhou; Li, Jing; Guo, Guo-Zhen

    2016-07-01

    A progressively expanded literature has been devoted in the past years to the noxious or beneficial effects of electromagnetic field (EMF) to Alzheimer׳s disease (AD). This study concerns the relationship between electromagnetic pulse (EMP) exposure and the occurrence of AD in rats and the underlying mechanisms, focusing on the role of oxidative stress (OS). 55 healthy male Sprague Dawley (SD) rats were used and received continuous exposure for 8 months. Morris water maze (MWM) test was conducted to test the ability of cognitive and memory. The level of OS was detected by superoxide dismutase (SOD) activity and glutathione (GSH) content. We found that long-term EMP exposure induced cognitive damage in rats. The content of β-amyloid (Aβ) protein in hippocampus was increased after long-term EMP exposure. OS of hippocampal neuron was detected. Western blotting and immunohistochemistry (IHC) assay showed that the content of Aβ protein and its oligomers in EMP-exposed rats were higher than that of sham-exposed rats. The content of Beta Site App Cleaving Enzyme (BACE1) and microtubule-associated protein 1 light chain 3-II (LC3-II) in EMP-exposed rats hippocampus were also higher than that of sham-exposed rats. SOD activity and GSH content in EMP-exposed rats were lower than sham-exposed rats (p<0.05). Several mechanisms were proposed based on EMP exposure-induced OS, including increased amyloid precursor protein (APP) aberrant cleavage. Although further study is needed, the present results suggest that long-term EMP exposure is harmful to cognitive ability in rats and could induce AD-like pathological manifestation. PMID:26972535

  9. Sleep-Deprivation Induces Changes in GABAB and mGlu Receptor Expression and Has Consequences for Synaptic Long-Term Depression

    OpenAIRE

    Tadavarty, Ramakrishna; Padmesh S Rajput; Wong, Jennifer M.; Kumar, Ujendra; Sastry, Bhagavatula R.

    2011-01-01

    Long term depression (LTD) in the CA1 region of the hippocampus, induced with a 20-Hz, 30 s tetanus to Schaffer collaterals, is enhanced in sleep-deprived (SD) rats. In the present study, we investigated the role of metabotropic glutamate receptors (mGluRs), γ-Aminobutyric acid (GABA) B receptors (GABAB-Rs) and N-methyl-D-aspartic acid receptors (NMDARs) in the LTD of the population excitatory postsynaptic potential (pEPSP). The requirement of Ca2+ from L- and T- type voltage-gated calcium ch...

  10. Inhibition of the group I mGluRs reduces acute brain damage and improves long-term histological outcomes after photothrombosis-induced ischaemia

    OpenAIRE

    Hailong Li; Nannan Zhang; Grace Sun; Shinghua Ding

    2013-01-01

    Group I mGluRs (metabotropic glutamate receptors), including mGluR1 and mGluR5, are GPCRs (G-protein coupled receptors) and play important roles in physiology and pathology. Studies on their role in cerebral ischaemia have provided controversial results. In this study, we used a PT (photothrombosis)-induced ischaemia model to investigate whether antagonists to the group I mGluRs may offer acute and long-term protective effects in adult mice. Our results demonstrated that administration with m...

  11. Long-Term Effects of Bone Marrow-Derived Mesenchymal Stem Cells in Dextran Sulfate Sodium-Induced Murine Chronic Colitis

    OpenAIRE

    Lee, Hyun Jung; Oh, Sun-Hee; Jang, Hui Won; Kwon, Ji-Hee; Lee, Kyoung Jin; Kim, Chung Hee; Park, Soo Jung; Hong, Sung Pil; Cheon, Jae Hee; Kim, Tae Il; Kim, Won Ho

    2016-01-01

    Background/Aims Bone marrow-derived mesenchymal stem cells (BM-MSCs) have shown beneficial effects in experimental colitis models, but the underlying mechanisms are not fully understood. We investigated the long-term effects of BM-MSCs, particularly in mice with chronic colitis. Methods Chronic colitis was induced by administering 3% dextran sulfate sodium (DSS) in a series of three cycles. BM-MSCs were injected intravenously into DSS-treated mice three times during the first cycle. On day 33...

  12. Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation

    DEFF Research Database (Denmark)

    Tremaroli, Valentina; Karlsson, Fredrik; Werling, Malin;

    2015-01-01

    Bariatric surgery is currently the most effective procedure for the treatment of obesity. Given the role of the gut microbiota in regulating host metabolism and adiposity, we investigated the long-term effects of bariatric surgery on the microbiome of patients randomized to Roux-en-Y gastric bypass...... or vertical banded gastroplasty and matched for weight and fat mass loss. The two surgical procedures induced similar and durable changes on the gut microbiome that were not dependent on body mass index and resulted in altered levels of fecal and circulating metabolites compared with obese controls...

  13. Long-term corticosterone exposure decreases insulin sensitivity and induces depressive-like behaviour in the C57BL/6NCrl mouse.

    Directory of Open Access Journals (Sweden)

    Eva L van Donkelaar

    Full Text Available Chronic stress or long-term administration of glucocorticoids disrupts the hypothalamus-pituitary-adrenal system leading to continuous high levels of glucocorticoids and insulin resistance (IR. This pre-diabetic state can eventually develop into type 2 diabetes mellitus and has been associated with a higher risk to develop depressive disorders. The mechanisms underlying the link between chronic stress, IR and depression remains unclear. The present study aimed to establish a stress-depression model in mice to further study the effects of stress-induced changes upon insulin sensitivity and behavioural consequences. A pilot study was conducted to establish the optimal administration route and a pragmatic measurement of IR. Subsequently, 6-month-old C57BL/6NCrl mice were exposed to long-term oral corticosterone treatment via the drinking water. To evaluate insulin sensitivity changes, blood glucose and plasma insulin levels were measured at different time-points throughout treatment and mice were behaviourally assessed in the elevated zero maze (EZM, forced swimming test (FST and open field test to reveal behavioural changes. Long-term corticosterone treatment increased body weight and decreased insulin sensitivity. The latter was revealed by a higher IR index and increased insulin in the plasma, whereas blood glucose levels remained unchanged. Corticosterone treatment induced longer immobility times in the FST, reflecting depressive-like behaviour. No effects were observed upon anxiety as measured in the EZM. The effect of the higher body weight of the CORT treated animals at time of testing did not influence behaviour in the EZM or FST, as no differences were found in general locomotor activity. Long-term corticosterone treatment via the drinking water reduces insulin sensitivity and induces depressive-like behaviour in the C57BL/6 mouse. This mouse model could thus be used to further explore the underlying mechanisms of chronic stress-induced T2

  14. Wood anatomy and carbon-isotope discrimination support long-term hydraulic deterioration as a major cause of drought-induced dieback.

    Science.gov (United States)

    Pellizzari, Elena; Camarero, J Julio; Gazol, Antonio; Sangüesa-Barreda, Gabriel; Carrer, Marco

    2016-06-01

    Hydraulic impairment due to xylem embolism and carbon starvation are the two proposed mechanisms explaining drought-induced forest dieback and tree death. Here, we evaluate the relative role played by these two mechanisms in the long-term by quantifying wood-anatomical traits (tracheid size and area of parenchyma rays) and estimating the intrinsic water-use efficiency (iWUE) from carbon isotopic discrimination. We selected silver fir and Scots pine stands in NE Spain with ongoing dieback processes and compared trees showing contrasting vigour (declining vs nondeclining trees). In both species earlywood tracheids in declining trees showed smaller lumen area with thicker cell wall, inducing a lower theoretical hydraulic conductivity. Parenchyma ray area was similar between the two vigour classes. Wet spring and summer conditions promoted the formation of larger lumen areas, particularly in the case of nondeclining trees. Declining silver firs presented a lower iWUE than conspecific nondeclining trees, but the reverse pattern was observed in Scots pine. The described patterns in wood anatomical traits and iWUE are coherent with a long-lasting deterioration of the hydraulic system in declining trees prior to their dieback. Retrospective quantifications of lumen area permit to forecast dieback in declining trees 2-5 decades before growth decline started. Wood anatomical traits provide a robust tool to reconstruct the long-term capacity of trees to withstand drought-induced dieback. PMID:26790660

  15. Plant diversity induces a shift of DOC concentration over time - results from long term and large scale experiment

    Science.gov (United States)

    Lange, Markus; Gleixner, Gerd

    2016-04-01

    Plant diversity has been demonstrated as a crucial factor for soil organic carbon (SOC) storage. The horizontal SOC formation in turn is strongly impacted by the relative small but consistent flow of dissolved organic carbon (DOC) in soils. In this process, pore water leaches plant material and already stored SOC while simultaneously these leachates are transported downwards. However, there is a big uncertainty about the drivers of DOC flux; in particular about the importance of biological processes. We investigated the impact of plant diversity and other biotic drivers on DOC concentrations and total DOC fluxes (concentration × sampled water amount). In addition, we considered abiotic factors such as weather and soil conditions to assess the relative importance of biotic and abiotic drivers and how their importance changes over time. We used a comprehensive data set, gathered in the frame of the long-term biodiversity experiment "The Jena Experiment". Permanent monitoring started directly after establishment of the field site in 2002 and is still running. This enabled us to trace the impact of plant communities with their increasing establishment over the time on DOC concentration. We found the amount of sampled pore water best explained by rainfall, while it was not related to plant associated variables. Directly after establishing the experimental site, DOC concentrations were highest and then decreasing with time. In the first period of the experiment plant diversity had no or even a slightly negative impact on DOC concentrations. The direction of the plant diversity effect on DOC concentrations changed over time; namely in later phases we observed highest DOC concentrations on plots with high plant diversity. Moreover, DOC concentrations were negatively affected by increased amounts of sampled pore water indicating a dilution effect. Even though this impact was highly significant; its effect size was even less pronounced at later time points. In summary

  16. Collectes à long terme

    CERN Document Server

    Collectes à long terme

    2014-01-01

    En cette fin d’année 2014 qui approche à grands pas, le Comité des Collectes à Long Terme remercie chaleureusement ses fidèles donatrices et donateurs réguliers pour leurs contributions à nos actions en faveur des plus démunis de notre planète. C’est très important, pour notre Comité, de pouvoir compter sur l’appui assidu que vous nous apportez. Depuis plus de 40 ans maintenant, le modèle des CLT est basé principalement sur des actions à long terme (soit une aide pendant 4-5 ans par projet, mais plus parfois selon les circonstances), et sa planification demande une grande régularité de ses soutiens financiers. Grand MERCI à vous ! D’autres dons nous parviennent au cours de l’année, et ils sont aussi les bienvenus. En particulier, nous tenons à remercier...

  17. Effects of long term feeding of raw soya bean flour on virus- induced pancreatic carcinogenesis in guinea fowl

    NARCIS (Netherlands)

    Kirev, T.; Woutersen, R.A.; Kiril, A.

    1999-01-01

    The effects of a diet enriched with 25% raw soya bean flour (RSF) on the pancreas and on the avian retrovirus Pts 56-induced pancreatic carcinogenesis in guinea fowl were studied. It has been shown that prolonged RSF feeding of new-hatched virus-infected and uninfected guinea fowl-poults induced enl

  18. [Radiation-induced damage of mitochondrial genome and its role in long-term effects of irradiation].

    Science.gov (United States)

    Berogovskaia, N N; Savich, A V

    1994-01-01

    The role of mt-genome mutations in radiation-induced carcinogenesis has been hypothesized. The data on radiation chemistry of nucleic acids has been used to evaluate mutagenic effect of carcinogenic doses of ionizing radiation. The assumptions about the ways of biological augmentation of primary radiation-induced lesions in mt-genome has been given. PMID:8069366

  19. The effects of long-term administration of tadalafil on STZ-induced diabetic rats with erectile dysfunction via a local antioxidative mechanism

    Institute of Scientific and Technical Information of China (English)

    Yun Chen; Xiao-Xin Li; Hao-Cheng Lin; Xue-Feng Qiu; Jing Gao; Yu-Tian Dai; Run Wang

    2012-01-01

    Type 5 phosphodiesterase inhibitors (PDE51s) are well known being effective viathe nitric oxide and cyclic guanosine monophosphate (NO-cGMP) pathway and are widely used in the treatment of diabetic erectile dysfunction (ED).However,it is unclear whether other pathways may be involved in the treatment of diabetic ED with PDE51s.The purpose of this study was to clarify the role of antioxidants in diabetic ED treatment through the long-term administration of PDE51s.Three groups of Sprague-Dawley rats were utilized:Group N,the normal control; Group D,streptozotocin (STZ)-induced diabetic rats as a control; and Group D+T,STZ-induced diabetic rats who received oral administration of tadalafil for 8 weeks.Erectile function was assessed by intracavernous pressure (ICP) and mean arterial pressure (MAP) during electrical stimulation of the cavernous nerve before euthanasia.The levels of malondialdehyde (MDA),superoxide dismutase (SOD) and mitochondrial membrane potential (MMP) of cavernous tissue were assessed by biochemical analysis.The morphology of mitochondria was observed by electron microscopy.The ICP/MAP ratio was higher in Group D+T than in Group D (P<0.05).The levels of MDA decreased and the activities of SOD increased in Group D+T in comparison with Group D (P<0.05).The mitochondrial membrane potential level of cavernous tissue in diabetic rats was partially recovered by tadalafil treatment for 8 weeks.The morphology changes of mitochondria were also remarkably ameliorated in Group D+T.Collectively,the long-term administration of tadalafil in diabetic rats partially reduced oxidative stress lesions of the penis viaa local antioxidative stress pathway.Long-term dosages of tadalafil given once daily beginning soon after the onset of diabetes may aid in preventing rats from developing diabetic ED.

  20. Long-term fluoxetine treatment induces input-specific LTP and LTD impairment and structural plasticity in the CA1 hippocampal subfield.

    Directory of Open Access Journals (Sweden)

    Francisco J Rubio

    2013-05-01

    Full Text Available Antidepressant drugs are usually administered for long time for the treatment of major depressive disorder. However, they are also prescribed in several additional psychiatric conditions as well as during long term maintenance treatments. Antidepressants induce adaptive changes in several forebrain structures which include modifications at glutamatergic synapses. We recently found that repetitive administration of the selective serotonin reuptake inhibitor fluoxetine to naϊve adult male rats induced an increase of mature, mushroom-type dendritic spines in several forebrain regions. This was associated with an increase of GluA2-containing α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPA-Rs in telencephalic postsynaptic densities. To unravel the functional significance of such a synaptic re-arrangement, we focused on glutamate neurotransmission in the hippocampus. We evaluated the effect of four weeks of treatment with 0.7 mg/kg of fluoxetine on long-term potentiation (LTP and long-term depression (LTD in the Schaffer collateral-CA1 synapses and the perforant path-CA1 synapses. Recordings in hippocampal slices revealed profound deficits in LTP and LTD at Schaffer collateral-CA1 synapses associated to increased spine density and enhanced presence of mushroom-type spines, as revealed by Golgi staining. However, the same treatment had neither an effect on spine morphology, nor on LTP and LTD at perforant path-CA1 synapses. Cobalt staining experiments revealed decreased AMPA-R Ca2+ permeability in the stratum radiatum together with increased GluA2-containing, Ca2+-impermeable AMPA-Rs. Therefore, 4 weeks of fluoxetine treatment promoted structural and functional adaptations in CA1 neurons in a pathway-specific manner that were selectively associated with impairment of activity-dependent plasticity at Schaffer collateral-CA1 synapses.

  1. Combined Anti-CD154/CTLA4Ig Costimulation Blockade-Based Therapy Induces Donor-Specific Tolerance to Vascularized Osteomyocutaneous Allografts.

    Science.gov (United States)

    Lin, C H; Wang, Y L; Anggelia, M R; Chuang, W Y; Cheng, H Y; Mao, Q; Zelken, J A; Lin, C H; Zheng, X X; Lee, W P A; Brandacher, G

    2016-07-01

    Tolerance induction by means of costimulation blockade has been successfully applied in solid organ transplantation; however, its efficacy in vascularized composite allotransplantation, containing a vascularized bone marrow component and thus a constant source of donor-derived stem cells, remains poorly explored. In this study, osteomyocutaneous allografts (alloOMCs) from Balb/c (H2(d) ) mice were transplanted into C57BL/6 (H2(b) ) recipients. Immunosuppression consisted of 1 mg anti-CD154 on day 0, 0.5 mg CTLA4Ig on day 2 and rapamycin (RPM; 3 mg/kg per day from days 0-7, then every other day for 3 weeks). Long-term allograft survival, donor-specific tolerance and donor-recipient cell trafficking were evaluated. Treatment with costimulation blockade plus RPM resulted in long-term graft survival (>120 days) of alloOMC in 12 of 15 recipients compared with untreated controls (median survival time [MST] ≈10.2 ± 0.8 days), RPM alone (MST ≈33 ± 5.5 days) and costimulation blockade alone (MST ≈45.8 ± 7.1 days). Donor-specific hyporesponsiveness in recipients with viable grafts was demonstrated in vitro. Evidence of donor-specific tolerance was further assessed in vivo by secondary donor-specific skin graft survival and third-party graft rejection. A significant increase of Foxp3(+) regulatory T cells was evident in tolerant animals. Donor cells populated peripheral blood, thymus, and both donor and recipient bone marrow. Consequently, combined anti-CD154/CTLA4Ig costimulation blockade-based therapy induces donor-specific tolerance in a stringent murine alloOMC transplant model. PMID:26914847

  2. ''Hair-on-end'' skull induced by long-term G-CSF treatment in severe congenital neutropenia

    Energy Technology Data Exchange (ETDEWEB)

    Albert, Michael H. [Dr. von Haunersches Kinderspital, Department of Haematology/Oncology, Munich (Germany); Notheis, Gundula; Wintergerst, Uwe [Dr. von Haunersches Kinderspital, Department of Infection/Immunity, Munich (Germany); Born, Christine [Klinikum Innenstadt, General Radiology, Munich (Germany); Schneider, Karl [Dr. von Haunersches Kinderspital, Department of Pediatric Radiology, Munich (Germany)

    2007-02-15

    ''Hair-on-end'' skull changes are typically seen in individuals suffering from thalassaemia. They are induced by widening of the diploic space due to marrow expansion that is a consequence of ineffective and excessive erythropoiesis. We present a child with severe congenital neutropenia who exhibited the typical hair-on-end sign on plain skull radiographs and MRI. In this patient the skull changes were very likely induced by the expansion of white blood cell precursors induced by long-term daily injections of recombinant human granulocyte colony stimulating factor (G-CSF) to treat his confounding disease. This case report is the first description of hair-on-end changes associated with the use of G-CSF. (orig.)

  3. Continuous subcutaneous waking day apomorphine in the long term treatment of levodopa induced interdose dyskinesias in Parkinson's disease

    OpenAIRE

    Colzi, A; Turner, K.; Lees, A.

    1998-01-01

    OBJECTIVES—To determine whether continous waking day dopaminergic stimulation with the dopamine agonist apomorphine can reduce levodopa induced dyskinesias in Parkinson's disease
METHODS—19 patients with severe unpredictable refractory motor fluctuations and functionally disabling levodopa induced dyskinesias were treated with continuous subcutaneoius apomorphine monotherapy for a minimum duration of 2.7 years
RESULTS—A mean 65% reduction in dyskinetic severity and a mean 85...

  4. Application of {sup 1}H-NMR-based metabolomics for detecting injury induced by long-term microwave exposure in Wistar rats' urine

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Li-Feng; Peng, Rui-Yun; Wang, Shui-Ming; Gao, Ya-Bing; Dong, Ji; Zhao, Li; Li, Xiang; Zuo, Hong-Yan; Wang, Chang-Zhen [Beijing Institute of Radiation Medicine, Laboratory of Pathology, Beijing (China); Hu, Xiang-Jun [Beijing Institute of Radiation Medicine, Beijing (China); Gao, Rong-Lian [Beijing Institute of Radiation Medicine, Laser Medicine, Beijing (China); Su, Zhen-Tao [Beijing Institute of Radiation Medicine, Radiation Protection, Beijing (China); Feng, Xin-Xing [Chinese Academy of Medical Sciences, Endocrine and Cardiovascular Center, Fuwai Hospital and Cardiovascular Institute, Beijing (China)

    2012-07-15

    There has been growing public concern regarding exposure to microwave fields as a potential human health hazard. This study aimed to identify sensitive biochemical indexes for the detection of injury induced by microwave exposure. Male Wistar rats were exposed to microwaves for 6 min per day, 5 days per week over a period of 1 month at an average power density of 5 mW/cm{sup 2} (specific absorption rate of 2.1 W/kg). Urine specimens were collected over 24 h in metabolic cages at 7 days, 21 days, 2 months, and 6 months after exposure. {sup 1}H NMR spectroscopy data were analyzed using multivariate statistical techniques. Urine metabolic profiles of rats after long-term microwave exposure were significantly differentiated from those of sham-treated controls using principal component analysis or partial least squares discriminant analysis. Significant differences in low molecular weight metabolites (acetate, succinate, citrate, ketoglutarate, glucose, taurine, phenylalanine, tyrosine, and hippurate) were identified in the 5 mW/cm{sup 2} microwave exposure group compared with the sham-treated controls at 7 days, 21 days, and 2 months. Metabolites returned to normal levels by 6 months after exposure. These data indicated that these metabolites were related to the perturbations of energy metabolism particularly in the tricarboxylic acid cycle, and the metabolism of amino acids, monoamines, and choline in urine represent potential indexes for the detection of injury induced by long-term microwave exposure. (orig.)

  5. Long term morphological modelling

    DEFF Research Database (Denmark)

    Kristensen, Sten Esbjørn; Deigaard, Rolf; Taaning, Martin; Fredsøe, Jørgen; Drønen, Nils; Hjelmager Jensen, Jacob

    2010-01-01

    concept often used in one-line modelling of cross-shore shifting of an otherwise constant shape cross-shore profile is applied for the case of a groyne and a detached breakwater. In the case of alongshore bar/nourishment migration an alternative parameterization is adopted. All examples are presented......A morphological modelling concept for long term nearshore morphology is proposed and examples of its application are presented and discussed. The model concept combines parameterised representations of the cross-shore morphology, with a 2DH area model for waves, currents and sediment transport in...... the surf zone. Two parameterization schemes are tested for two different morphological phenomena: 1) Shoreline changes due to the presence of coastal structures and 2) alongshore migration of a nearshore nourishment and a bar by-passing a harbour. In the case of the shoreline evolution calculations, a...

  6. Detecting long-term low-irradiance stress and water stress of trees with laser-induced fluorescence measurements

    International Nuclear Information System (INIS)

    The objective of this study was to find simple and objective methods of diagnosing the ailments of trees in indoor spaces, such as atriums. In this study, two simple diagnostics were compared. One was the analysis of the laser-induced fluorescence spectra of leaves and the other was the analysis of the laser-induced chlorophyll-fluorescence induction kinetics (Kautsky effect). In the latter analysis, second time derivatives of the induction-kinetics curves were used. Cinnamomum camphora and Quercus myrsinifolia grown under different light conditions and Cinnamomum camphora under water stress were used in the experiments. The effects of low irradiance were detected in both the induction kinetics and the spectra; however, the effects of water stress were detected in the induction kinetics only. These results indicate the possibility of utilizing laser-induced-fluorescence induction-kinetics for diagnosing the ailments of trees. (author)

  7. Blockaded six- and eight-wave mixing processes tailored by electromagnetically induced transparency scissors

    Science.gov (United States)

    Zheng, H. B.; Yao, X.; Zhang, Z. Y.; Che, J. L.; Zhang, Y. Q.; Zhang, Y. P.; Xiao, M.

    2014-04-01

    We report the first experimental observations of the blockaded six- and eight-wave mixing processes in a collective multi-level Rydberg atomic ensemble tailored by multi-channel scissors and created by three coexisting electromagnetically induced transparency (EIT) windows. The interplay between the dressed-state effect and the Rydberg blockade caused by strong van der Waals interactions is investigated when several parameters in the excitation lasers are changed. Blockaded multi-wave mixing (MWM) signals are obtained when the coupling frequency detuning is changed, which is improved to give multiple channels when the probe detuning is scanned. Such MWM signals tailored by EIT scissors produce a much narrower linewidth and therefore are suitable for application in long-distance quantum communication. The advantages of having multi-channel blockaded MWM signals also makes potential applications in demonstrating multi-channel entanglement possible and improves the performance of quantum computation with Rydberg atoms.

  8. Blockaded six- and eight-wave mixing processes tailored by electromagnetically induced transparency scissors

    International Nuclear Information System (INIS)

    We report the first experimental observations of the blockaded six- and eight-wave mixing processes in a collective multi-level Rydberg atomic ensemble tailored by multi-channel scissors and created by three coexisting electromagnetically induced transparency (EIT) windows. The interplay between the dressed-state effect and the Rydberg blockade caused by strong van der Waals interactions is investigated when several parameters in the excitation lasers are changed. Blockaded multi-wave mixing (MWM) signals are obtained when the coupling frequency detuning is changed, which is improved to give multiple channels when the probe detuning is scanned. Such MWM signals tailored by EIT scissors produce a much narrower linewidth and therefore are suitable for application in long-distance quantum communication. The advantages of having multi-channel blockaded MWM signals also makes potential applications in demonstrating multi-channel entanglement possible and improves the performance of quantum computation with Rydberg atoms. (paper)

  9. JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage.

    Science.gov (United States)

    Becattini, Barbara; Zani, Fabio; Breasson, Ludovic; Sardi, Claudia; D'Agostino, Vito Giuseppe; Choo, Min-Kyung; Provenzani, Alessandro; Park, Jin Mo; Solinas, Giovanni

    2016-09-01

    Obesity and insulin resistance are associated with oxidative stress, which may be implicated in the progression of obesity-related diseases. The kinase JNK1 has emerged as a promising drug target for the treatment of obesity and type 2 diabetes. JNK1 is also a key mediator of the oxidative stress response, which can promote cell death or survival, depending on the magnitude and context of its activation. In this article, we describe a study in which the long-term effects of JNK1 inactivation on glucose homeostasis and oxidative stress in obese mice were investigated for the first time. Mice lacking JNK1 (JNK1(-/-)) were fed an obesogenic high-fat diet (HFD) for a long period. JNK1(-/-) mice fed an HFD for the long term had reduced expression of antioxidant genes in their skin, more skin oxidative damage, and increased epidermal thickness and inflammation compared with the effects in control wild-type mice. However, we also observed that the protection from obesity, adipose tissue inflammation, steatosis, and insulin resistance, conferred by JNK1 ablation, was sustained over a long period and was paralleled by decreased oxidative damage in fat and liver. We conclude that compounds targeting JNK1 activity in brain and adipose tissue, which do not accumulate in the skin, may be safer and most effective.-Becattini, B., Zani, F., Breasson, L., Sardi, C., D'Agostino, V. G., Choo, M.-K., Provenzani, A., Park, J. M., Solinas, G. JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage. PMID:27230858

  10. Long-term exposure of A549 cells to titanium dioxide nanoparticles induces DNA damage and sensitizes cells towards genotoxic agents.

    Science.gov (United States)

    Armand, Lucie; Tarantini, Adeline; Beal, David; Biola-Clier, Mathilde; Bobyk, Laure; Sorieul, Sephanie; Pernet-Gallay, Karin; Marie-Desvergne, Caroline; Lynch, Iseult; Herlin-Boime, Nathalie; Carriere, Marie

    2016-09-01

    Titanium dioxide nanoparticles (TiO2-NPs) are one of the most produced NPs in the world. Their toxicity has been studied for a decade using acute exposure scenarios, i.e. high exposure concentrations and short exposure times. In the present study, we evaluated their genotoxic impact using long-term and low concentration exposure conditions. A549 alveolar epithelial cells were continuously exposed to 1-50 μg/mL TiO2-NPs, 86% anatase/14% rutile, 24 ± 6 nm average primary diameter, for up to two months. Their cytotoxicity, oxidative potential and intracellular accumulation were evaluated using MTT assay and reactive oxygen species measurement, transmission electron microscopy observation, micro-particle-induced X-ray emission and inductively-coupled plasma mass spectroscopy. Genotoxic impact was assessed using alkaline and Fpg-modified comet assay, immunostaining of 53BP1 foci and the cytokinesis-blocked micronucleus assay. Finally, we evaluated the impact of a subsequent exposure of these cells to the alkylating agent methyl methanesulfonate. We demonstrate that long-term exposure to TiO2-NPs does not affect cell viability but causes DNA damage, particularly oxidative damage to DNA and increased 53BP1 foci counts, correlated with increased intracellular accumulation of NPs. In addition, exposure over 2 months causes cellular responses suggestive of adaptation, characterized by decreased proliferation rate and stabilization of TiO2-NP intracellular accumulation, as well as sensitization to MMS. Taken together, these data underline the genotoxic impact and sensitization effect of long-term exposure of lung alveolar epithelial cells to low levels of TiO2-NPs. PMID:26785166

  11. Enhanced long term potentiation and decreased AMPA receptor desensitization in the acute period following a single kainate induced early life seizure.

    Science.gov (United States)

    O'Leary, Heather; Bernard, Paul B; Castano, Anna M; Benke, Tim A

    2016-03-01

    Neonatal seizures are associated with long term disabilities including epilepsy and cognitive deficits. Using a neonatal seizure rat model that does not develop epilepsy, but develops a phenotype consistent with other models of intellectual disability (ID) and autism spectrum disorders (ASD), we sought to isolate the acute effects of a single episode of early life seizure on hippocampal CA1 synaptic development and plasticity. We have previously shown chronic changes in glutamatergic synapses, loss of long term potentiation (LTP) and enhanced long term depression (LTD), in the adult male rat ~50days following kainic acid (KA) induced early life seizure (KA-ELS) in post-natal (P) 7day old male Sprague-Dawley rats. In the present work, we examined the electrophysiological properties and expression levels of glutamate receptors in the acute period, 2 and 7days, post KA-ELS. Our results show for the first time enhanced LTP 7days after KA-ELS, but no change 2days post KA-ELS. Additionally, we report that ionotropic α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid type glutamate receptor (AMPAR) desensitization is decreased in the same time frame, with no changes in AMPAR expression, phosphorylation, or membrane insertion. Inappropriate enhancement of the synaptic connections in the acute period after the seizure could alter the normal patterning of synaptic development in the hippocampus during this critical period and contribute to learning deficits. Thus, this study demonstrates a novel mechanism by which KA-ELS alters early network properties that potentially lead to adverse outcomes. PMID:26706598

  12. Parental knowledge reduces long term anxiety induced by false-positive test results after newborn screening for cystic fibrosis

    NARCIS (Netherlands)

    Vernooij-van Langen, A.M.M.; Pal, S.M. van der; Reijntjens, A.J.T.; Loeber, J.G.; Dompeling, E.; Dankert-Roelse, J.E.

    2014-01-01

    Background: False-positive screening results in newborn screening for cystic fibrosis may lead to parental stress, family relationship problems and a changed perception of the child's health. Aim of the study: To evaluate whether parental anxiety induced by a false positive screening result disappea

  13. Parishin C's prevention of Aβ 1-42-induced inhibition of long-term potentiation is related to NMDA receptors.

    Science.gov (United States)

    Liu, Zhihui; Wang, Weiping; Feng, Nan; Wang, Ling; Shi, Jiangong; Wang, Xiaoliang

    2016-05-01

    The rhizome of Gastrodia elata (GE), a herb medicine, has been used for treatment of neuronal disorders in Eastern Asia for hundreds of years. Parishin C is a major ingredient of GE. In this study, the i.c.v. injection of soluble Aβ 1-42 oligomers model of LTP injury was used. We investigated the effects of parishin C on the improvement of LTP in soluble Aβ 1-42 oligomer-injected rats and the underlying electrophysiological mechanisms. Parishin C (i.p. or i.c.v.) significantly ameliorated LTP impairment induced by i.c.v. injection of soluble Aβ 1-42 oligomers. In cultured hippocampal neurons, soluble Aβ 1-42 oligomers significantly inhibited NMDAR currents while not affecting AMPAR currents and voltage-dependent currents. Pretreatment with parishin C protected NMDA receptor currents from the damage induced by Aβ. In summary, parishin C improved LTP deficits induced by soluble Aβ 1-42 oligomers. The protection by parishin C against Aβ-induced LTP damage might be related to NMDA receptors. PMID:27175329

  14. Parishin C's prevention of Aβ1–42-induced inhibition of long-term potentiation is related to NMDA receptors

    Science.gov (United States)

    Liu, Zhihui; Wang, Weiping; Feng, Nan; Wang, Ling; Shi, Jiangong; Wang, Xiaoliang

    2016-01-01

    The rhizome of Gastrodia elata (GE), a herb medicine, has been used for treatment of neuronal disorders in Eastern Asia for hundreds of years. Parishin C is a major ingredient of GE. In this study, the i.c.v. injection of soluble Aβ1–42 oligomers model of LTP injury was used. We investigated the effects of parishin C on the improvement of LTP in soluble Aβ1–42 oligomer–injected rats and the underlying electrophysiological mechanisms. Parishin C (i.p. or i.c.v.) significantly ameliorated LTP impairment induced by i.c.v. injection of soluble Aβ1–42 oligomers. In cultured hippocampal neurons, soluble Aβ1–42 oligomers significantly inhibited NMDAR currents while not affecting AMPAR currents and voltage-dependent currents. Pretreatment with parishin C protected NMDA receptor currents from the damage induced by Aβ. In summary, parishin C improved LTP deficits induced by soluble Aβ1–42 oligomers. The protection by parishin C against Aβ-induced LTP damage might be related to NMDA receptors. PMID:27175329

  15. Nitric oxide synthase inhibitor improves de novo and long-term L-DOPA-induced dyskinesia in hemiparkinsonian rats

    Directory of Open Access Journals (Sweden)

    Fernando Eduardo Padovan-Neto

    2011-06-01

    Full Text Available Inhibitors of neuronal and endothelial nitric oxide synthase decrease l-3,4-dihidroxifenilalanine (L-DOPA-induced dyskinesias in rodents. The mechanism of nitric oxide inhibitor action is unknown. The aims of the present study were to investigate the decrease of L-DOPA-induced abnormal involuntary movements in 6-hydroxydopamine (6-OHDA-lesioned rats by nitric oxide inhibitors following either acute or chronic treatment. The primary findings of this study were that NG-nitro-L-Arginine, an inhibitor of endothelial and neuronal nitric oxide synthase, attenuated abnormal involuntary movements induced by chronic and acute L-DOPA. In contrast, rotational behavior was attenuated only after chronic L-DOPA. L-DOPA improved stepping test performance, and its chronic administration did not alter open field behavior. Our results indicated a correlation between apomorphine-induced rotation and the decrease in the number of adjusting steps performed with the contralateral forepaw in the 6-OHDA-lesioned rats.The 6-OHDA lesion and the L-DOPA treatment induced a bilateral increase (1.5 times in the nNOS protein and nNOS mRNA in the striatum and in the frontal cortex. There was a parallel increase, bilaterally, of the FosB/ΔFosB, primarily in the ipsilateral striatum. The exception was in the contralateral striatum and the ipsilateral frontal cortex, where chronic L-DOPA treatment induced an increase of approximately 10 times the nNOS mRNA. Our results provided further evidence of an anti-dyskinetic effect of NOS inhibitor. The effect appeared under L-DOPA acute and chronic treatment. The L-DOPA treatment also revealed an over-expression of the neuronal NOS in the frontal cortex and striatum. Our results corroborated findings that L-DOPA-induced rotation differs between acute and chronic treatment. The effect of the NOS inhibitor conceivably relied on the L-DOPA structural modifications in the parkinsonian brain. Taken together, these data provided a rationale

  16. Long-term therapy of interferon-alpha induced pulmonary arterial hypertension with different PDE-5 inhibitors: a case report

    Directory of Open Access Journals (Sweden)

    Baumann Gert

    2005-09-01

    Full Text Available Abstract background Interferon alpha2 is widely used in hepatitis and high-risk melanoma. Interferon-induced pulmonary arterial hypertension as a side effect is rare. Case presentation We describe a melanoma patient who developed severe pulmonary arterial hypertension 30 months after initiation of adjuvant interferon alpha2b therapy. Discontinuation of interferon did not improve pulmonary arterial hypertension. This patient could be treated successfully with phosphodiesterase-5 inhibitor therapy. Conclusion This is only the 5th case of interferon-induced pulmonary arterial hypertension and the first documented case where pulmonary arterial hypertension was not reversible after termination of interferon alpha2 therapy. If interferon alpha2 treated patients develop respiratory symptoms, pulmonary arterial hypertension should be considered in the differential diagnosis. For these patients phosphodiesterase-5 inhibitors, e.g. sildenafil or vardenafil, could be an effective therapeutic approach.

  17. Long-term ω-3 fatty acid supplementation induces anti-stress effects and improves learning in rats

    OpenAIRE

    Pérez, Miguel Á; Terreros, Gonzalo; Dagnino-Subiabre, Alexies

    2013-01-01

    Chronic stress leads to secretion of the adrenal steroid hormone corticosterone, inducing hippocampal atrophy and dendritic hypertrophy in the rat amygdala. Both alterations have been correlated with memory impairment and increased anxiety. Supplementation with ω-3 fatty acids improves memory and learning in rats. The aim of this study was to evaluate the effects of ω-3 supplementation on learning and major biological and behavioral stress markers. Male Sprague–Dawley rats were randomly assig...

  18. Test-retest reliability of 10 Hz conditioning electrical stimulation inducing long-term potentiation (LTP)-like pain amplification in humans

    DEFF Research Database (Denmark)

    Xia, Weiwei; Mørch, Carsten Dahl; Andersen, Ole Kæseler

    2016-01-01

    BACKGROUND: 10 Hz conditioning electrical stimulation (CES) has been shown to induce long-term potentiation (LTP)-like pain amplification similar to traditional 100 Hz CES in healthy humans. The aim of this study was to assess the test-retest reliability and to estimate sample sizes required for...... acceptable reliability both in crossover and parallel designs (Ncr = 3, Np = 13). Pain ratings to SES were reliable, but with large estimated sample sizes (Ncr = 634, Np = 11310) due to the minor pain amplification. CONCLUSIONS: The reliability of 10 Hz CES was acceptable in inducing LTP-like effects in the...... assessments of superficial blood flow, heterotopic mechanical hyperalgesia, and dysesthesia in terms of sample sizes for future crossover study designs....

  19. A New View of Radiation-Induced Cancer: Integrating Short- and Long-Term Processes. Part II: Second Cancer Risk Estimation

    Science.gov (United States)

    Shuryak, Igor; Brenner, David J.; Hahnfeldt, Philip; Hlatky, Lynn; Sachs, Rainer K.

    2009-01-01

    As the number of cancer survivors grows, prediction of radiotherapy-induced second cancer risks becomes increasingly important. Because the latency period for solid tumors is long, the risks of recently introduced radiotherapy protocols are not yet directly measurable. In the accompanying article, we presented a new biologically based mathematical model, which, in principle, can estimate second cancer risks for any protocol. The novelty of the model is that it integrates, into a single formalism, mechanistic analyses of pre-malignant cell dynamics on two different time scales: short-term during radiotherapy and recovery; long-term during the entire life span. Here, we apply the model to nine solid cancer types (stomach, lung, colon, rectal, pancreatic, bladder, breast, central nervous system, and thyroid) using data on radiotherapy-induced second malignancies, on Japanese atomic bomb survivors, and on background US cancer incidence. Potentially, the model can be incorporated into radiotherapy treatment planning algorithms, adding second cancer risk as an optimization criterion.

  20. Parenteral adenoviral boost enhances BCG induced protection, but not long term survival in a murine model of bovine TB.

    Science.gov (United States)

    Kaveh, Daryan A; Garcia-Pelayo, M Carmen; Webb, Paul R; Wooff, Esen E; Bachy, Véronique S; Hogarth, Philip J

    2016-07-25

    Boosting BCG using heterologous prime-boost represents a promising strategy for improved tuberculosis (TB) vaccines, and adenovirus (Ad) delivery is established as an efficacious boosting vehicle. Although studies demonstrate that intranasal administration of Ad boost to BCG offers optimal protection, this is not currently possible in cattle. Using Ad vaccine expressing the mycobacterial antigen TB10.4 (BCG/Ad-TB10.4), we demonstrate, parenteral boost of BCG immunised mice to induce specific CD8(+) IFN-γ producing T cells via synergistic priming of new epitopes. This induces significant improvement in pulmonary protection against Mycobacterium bovis over that provided by BCG when assessed in a standard 4week challenge model. However, in a stringent, year-long survival study, BCG/Ad-TB10.4 did not improve outcome over BCG, which we suggest may be due to the lack of additional memory cells (IL-2(+)) induced by boosting. These data indicate BCG-prime/parenteral-Ad-TB10.4-boost to be a promising candidate, but also highlight the need for further understanding of the mechanisms of T cell priming and associated memory using Ad delivery systems. That we were able to generate significant improvement in pulmonary protection above BCG with parenteral, rather than mucosal administration of boost vaccine is critical; suggesting that the generation of effective mucosal immunity is possible, without the risks and challenges of mucosal administration, but that further work to specifically enhance sustained protective immunity is required. PMID:27317453

  1. H2-receptor blockade and exercise-induced asthma.

    OpenAIRE

    Nogrady, S G; Hahn, A G

    1984-01-01

    While in vitro studies suggest that H2-receptor blockade enhances mediator release from bronchial mast cells and leads to bronchoconstriction, in vivo studies have given conflicting results. Eight asthmatic subjects were given cimetidine 800 mg and placebo double-blind on different days. Baseline values of forced expiratory volume in one second (FEV1) were obtained before an 8 min standardized exercise test using a bicycle ergometer. Subjects inhaled cold, dry air and exercise on cimetidine a...

  2. Introduction: Long term prediction

    International Nuclear Information System (INIS)

    Making a decision upon the right choice of a material appropriate to a given application should be based on taking into account several parameters as follows: cost, standards, regulations, safety, recycling, chemical properties, supplying, transformation, forming, assembly, mechanical and physical properties as well as the behaviour in practical conditions. Data taken from a private communication (J.H.Davidson) are reproduced presenting the life time range of materials from a couple of minutes to half a million hours corresponding to applications from missile technology up to high-temperature nuclear reactors or steam turbines. In the case of deep storage of nuclear waste the time required is completely different from these values since we have to ensure the integrity of the storage system for several thousand years. The vitrified nuclear wastes should be stored in metallic canisters made of iron and carbon steels, stainless steels, copper and copper alloys, nickel alloys or titanium alloys. Some of these materials are passivating metals, i.e. they develop a thin protective film, 2 or 3 nm thick - the so-called passive films. These films prevent general corrosion of the metal in a large range of chemical condition of the environment. In some specific condition, localized corrosion such as the phenomenon of pitting, occurs. Consequently, it is absolutely necessary to determine these chemical condition and their stability in time to understand the behavior of a given material. In other words the corrosion system is constituted by the complex material/surface/medium. For high level nuclear wastes the main features for resolving problem are concerned with: geological disposal; deep storage in clay; waste metallic canister; backfill mixture (clay-gypsum) or concrete; long term behavior; data needed for modelling and for predicting; choice of appropriate solution among several metallic candidates. The analysis of the complex material/surface/medium is of great importance

  3. Long-term activation of TLR3 by Poly(I:C induces inflammation and impairs lung function in mice

    Directory of Open Access Journals (Sweden)

    Alexopoulou Lena

    2009-06-01

    Full Text Available Abstract Background The immune mechanisms associated with infection-induced disease exacerbations in asthma and COPD are not fully understood. Toll-like receptor (TLR 3 has an important role in recognition of double-stranded viral RNA, which leads to the production of various inflammatory mediators. Thus, an understanding of TLR3 activation should provide insight into the mechanisms underlying virus-induced exacerbations of pulmonary diseases. Methods TLR3 knock-out (KO mice and C57B6 (WT mice were intranasally administered repeated doses of the synthetic double stranded RNA analog poly(I:C. Results There was a significant increase in total cells, especially neutrophils, in BALF samples from poly(I:C-treated mice. In addition, IL-6, CXCL10, JE, KC, mGCSF, CCL3, CCL5, and TNFα were up regulated. Histological analyses of the lungs revealed a cellular infiltrate in the interstitium and epithelial cell hypertrophy in small bronchioles. Associated with the pro-inflammatory effects of poly(I:C, the mice exhibited significant impairment of lung function both at baseline and in response to methacholine challenge as measured by whole body plethysmography and an invasive measure of airway resistance. Importantly, TLR3 KO mice were protected from poly(I:C-induced changes in lung function at baseline, which correlated with milder inflammation in the lung, and significantly reduced epithelial cell hypertrophy. Conclusion These findings demonstrate that TLR3 activation by poly(I:C modulates the local inflammatory response in the lung and suggest a critical role of TLR3 activation in driving lung function impairment. Thus, TLR3 activation may be one mechanism through which viral infections contribute toward exacerbation of respiratory disease.

  4. Long-term Fenretinide treatment prevents high-fat diet-induced obesity, insulin resistance, and hepatic steatosis

    OpenAIRE

    Preitner, Frederic; Mody, Nimesh; Graham, Timothy E; Peroni, Odile D.; Kahn, Barbara B.

    2009-01-01

    The synthetic retinoid Fenretinide (FEN) increases insulin sensitivity in obese rodents and is in early clinical trials for treatment of insulin resistance in obese humans with hepatic steatosis (46). We aimed to determine the physiological mechanisms for the insulin-sensitizing effects of FEN. Wild-type mice were fed a high-fat diet (HFD) with or without FEN from 4–5 wk to 36–37 wk of age (preventive study) or following 22 wk of HF diet-induced obesity (12 wk intervention study). Retinol-bin...

  5. Long-Term Preservation of Left Ventricular Systolic Function in Patients With Refractory Angina Pectoris and Inducible Myocardial Ischemia on Optimal Medical Therapy.

    Science.gov (United States)

    Slavich, Massimo; Maranta, Francesco; Fumero, Andrea; Godino, Cosmo; Giannini, Francesco; Oppizzi, Michele; Colombo, Antonio; Fragasso, Gabriele; Margonato, Alberto

    2016-05-15

    Refractory angina pectoris (RAP) represents a clinical condition characterized by frequent episodes of chest pain despite therapy optimization. According to myocardial stunning and myocardial hibernation definitions, RAP should represent the ideal condition for systolic dysfunction development. We aim to investigate the evolution of left ventricular (LV) function in patients with RAP. A retrospective study which encompasses 144 patients with RAP referred to our institution from 1999 to December 2014 was performed. Of them, 88 met the inclusion criteria, and LV function was assessed by echocardiography. All of them had persistent angina episodes on top of optimal medical therapy and evidence of significant inducible myocardial ischemia and no further revascularization options. Nitrates consumption rate, time of angina duration, and the number of angina attacks were evaluated. In the whole population, ejection fraction (EF) was 44% ± 2. EF was significantly lower in patients with previous myocardial infarction (41% ± 1.5 vs 51% ± 1.8, p 5 years (5 years 44% ± 2 [n = 44]; p 0.02). Long-term LV function in patients with RAP is generally preserved. A previous history of myocardial infarction is the only determinant in the development of systolic dysfunction. In conclusion, frequent angina attacks and a long-term history of angina are not apparently associated to worse LV function. PMID:27055755

  6. Cadmium-induced inhibition of photosynthesis and long-term acclimation to cadmium stress in the hyperaccumulator Thlaspi caerulescens.

    Science.gov (United States)

    Küpper, Hendrik; Parameswaran, Aravind; Leitenmaier, Barbara; Trtílek, Martin; Setlík, Ivan

    2007-01-01

    Acclimation of hyperaccumulators to heavy metal-induced stress is crucial for phytoremediation and was investigated using the hyperaccumulator Thlaspi caerulescens and the nonaccumulators T. fendleri and T. ochroleucum. Spatially and spectrally resolved kinetics of in vivo absorbance and fluorescence were measured with a novel fluorescence kinetic microscope. At the beginning of growth on cadmium (Cd), all species suffered from toxicity, but T. caerulescens subsequently recovered completely. During stress, a few mesophyll cells in T. caerulescens became more inhibited and accumulated more Cd than the majority; this heterogeneity disappeared during acclimation. Chlorophyll fluorescence parameters related to photochemistry were more strongly affected by Cd stress than nonphotochemical parameters, and only photochemistry showed acclimation. Cd acclimation in T. caerulescens shows that part of its Cd tolerance is inducible and involves transient physiological heterogeneity as an emergency defence mechanism. Differential effects of Cd stress on photochemical vs nonphotochemical parameters indicate that Cd inhibits the photosynthetic light reactions more than the Calvin-Benson cycle. Differential spectral distribution of Cd effects on photochemical vs nonphotochemical quenching shows that Cd inhibits at least two different targets in/around photosystem II (PSII). Spectrally homogeneous maximal PSII efficiency (F(v)/F(m)) suggests that in healthy T. caerulescens all chlorophylls fluorescing at room temperature are PSII-associated. PMID:17688582

  7. LONG TERM COLLECTIONS

    CERN Multimedia

    STAFF ASSOCIATION

    2010-01-01

    ACKNOWLEDGMENTS The Long-Term Collections (CLT) committee would like to warmly thank its faithful donors who, year after year, support our actions all over the world. Without you, all this would not be possible. We would like to thank, in particular, the CERN Firemen’s Association who donated 5000 CHF in the spring thanks to the sale of their traditional calendar, and the generosity of the CERN community. A huge thank you to the firemen for their devotion to our cause. And thank you to all those who have opened their door, their heart, and their purses! Similarly, we warmly thank the CERN Yoga Club once again for its wonderful donation of 2000 CHF we recently received. We would also like to tell you that all our projects are running well. Just to remind you, we are currently supporting the activities of the «Réflexe-Partage» Association in Mali; the training centre of «Education et Développement» in Abomey, Benin; and the orphanage and ...

  8. Estimates of the long-term U.S. economic impacts of global climate change-induced drought.

    Energy Technology Data Exchange (ETDEWEB)

    Ehlen, Mark Andrew; Loose, Verne W.; Warren, Drake E.; Vargas, Vanessa N.

    2010-01-01

    While climate-change models have done a reasonable job of forecasting changes in global climate conditions over the past decades, recent data indicate that actual climate change may be much more severe. To better understand some of the potential economic impacts of these severe climate changes, Sandia economists estimated the impacts to the U.S. economy of climate change-induced impacts to U.S. precipitation over the 2010 to 2050 time period. The economists developed an impact methodology that converts changes in precipitation and water availability to changes in economic activity, and conducted simulations of economic impacts using a large-scale macroeconomic model of the U.S. economy.

  9. Omega-3 fatty acids partially revert the metabolic gene expression profile induced by long-term calorie restriction.

    Science.gov (United States)

    López-Domínguez, José Alberto; Cánovas, Ángela; Medrano, Juan F; Islas-Trejo, Alma; Kim, Kyoungmi; Taylor, Sandra L; Villalba, José Manuel; López-Lluch, Guillermo; Navas, Plácido; Ramsey, Jon J

    2016-05-01

    Calorie restriction (CR) consistently extends longevity and delays age-related diseases across several animal models. We have previously shown that different dietary fat sources can modulate life span and mitochondrial ultrastructure, function and membrane fatty acid composition in mice maintained on a 40% CR. In particular, animals consuming lard as the main fat source (CR-Lard) lived longer than CR mice consuming diets with soybean oil (CR-Soy) or fish oil (CR-Fish) as the predominant lipid source. In the present work, a transcriptomic analysis in the liver and skeletal muscle was performed in order to elucidate possible mechanisms underlying the changes in energy metabolism and longevity induced by dietary fat in CR mice. After 8months of CR, transcription downstream of several mediators of inflammation was inhibited in liver. In contrast, proinflammatory signaling was increased in the CR-Fish versus other CR groups. Dietary fish oil induced a gene expression pattern consistent with increased transcriptional regulation by several cytokines (TNF, GM-CSF, TGF-β) and sex hormones when compared to the other CR groups. The CR-Fish also had lower expression of genes involved in fatty acid biosynthesis and increased expression of mitochondrial and peroxisomal fatty acid β-oxidation genes than the other CR diet groups. Our data suggest that a diet high in n-3 PUFA, partially reverts CR-related changes in gene expression of key processes, such as inflammation and steroid hormone signaling, and this may mitigate life span extension with CR in mice consuming diets high in fish oil. PMID:26875793

  10. Experimental Study on the Effect of Calcitonin in Osteoporosis Induced by the Immobilization and Long-Term Glucocorticoid

    International Nuclear Information System (INIS)

    It is well known that the glucocorticoid induces osteoporosis by suppression of the osteoblast, but its effect on the osteoclast has some controversy whether it activates or suppresses the osteoclast. If the calcitonin, which is known to suppress the osteoclast, prevents the osteoporosis by glucocorticoid, then the suppression of the osteoclast by the glucocorticoid is not so significant. And if the calcitonin increases the osteoblastic activity, Tc-99m MDP uptake will be increased in spite of the glucocorticoid effect on the osteoblast. The immobilization operation was performed to the right leg of male Wistar rats weighing about 200 gm each. For 16 weeks after operation, rats were injected glucocorticoid alone or glucocorticoid and calcitonin. The bone density was measured by means of photodensitometry under reference aluminum step wedge and Tc-99m MDP uptake was available to the index of the osteoblastic activity. 1. The bone density of femoral head was markedly reduced than that of femoral shaft following ratio of cancellous and cortical components in both site. 2. glucocorticoid caused decrease in bone density of spine and femur, and there is significantly increase of it when medication of glucocorticoid and calcitonin injection simultaneously than that of glucocorticoid. 3. Tc-99m MDP uptake was revealed significant reduction in medication of glucocorticoid but increase in glucocorticoid and calcitonin injection simultaneously in later experimental period. 4. There was a slight reduction in plasma osteocalcin in medication of glucocorticoid through experimental periods and an increase in its value in case of giving glucocorticoid and calcitonin simultaneously in later experimental period. From these results, we suggest that osteoporosis by immobilization is more pronounced by glucocorticoid hormone and osteoporosis induced by immobilization and glucocorticoid use is prevented by calcitonin administration with increasing osteoblastic activity.

  11. Atomic bomb irradiation-induced leukemias revisited. Summary data of 50 years-long term follow up study on survivors

    International Nuclear Information System (INIS)

    The Life Span Study (LSS) on 93,741 survivors (fixed cohort) and the Open City Study (OCS) on all survivors (unfixed) irrespective of whether they belonged to LSS or not, have been conducted in parallel over 45 years to ensure reliable case detection. We adopted the FAB classification for acute leukemias and for exposure dose of individual survivors, the new dosimetry system 1986 (DS86). In LSS, 221 leukemia cases were analysed. There was strong evidence of radiation-induced risks for acute myeloid leukemia (AML), acute lymphoid leukemia (ALL) and chronic myeloid leukemia (CML), but not for adult T-cell leukemia and chronic lymphocytic leukemia. There was also significant difference between three major types with respect to the effects of age at bombing and sex, and in the temporal pattern of the elevated risks. For AML the dose response function was non-linear, whereas there was no evidence against linearity for ALL and CML. The hypothesis of a 0.5 Gy threshold could be rejected for three major types of leukemia. Excess Absolute Risk (EAR) estimates in cases per 10,000 Person Year Sievert (PYSv) were 0.6, 1.1, 0.9 for ALL, AML and CML, respectively. The corresponding relative risk at 1.0 Sv were 9.1, 3.3, 6.2, respectively. Although childhood exposure <15 age at bombing apparently induced three major types, the age-related highest risk was observed for ALL. In OCS, 413 cases with DS86 estimates were used for analysis. Type specific incidence rates were calculated indirectly by using the over all incidence of leukemia from LSS data and multiplying these values by the corresponding proportions of cases in OCS. In conjunction with LSS data, the effects of radiation were significantly greater on the incidences of ALL and CML than on that of AML. In the high dose group there was a strong evidence for shorter incubation time and faster decline of elevated risk for ALL and CML than for AML. AML risk was apparently persistent through 1980. (K.H.)

  12. Atomic bomb irradiation-induced leukemias revisited. Summary data of 50 years-long term follow up study on survivors

    Energy Technology Data Exchange (ETDEWEB)

    Tomonaga, Masao [Nagasaki Univ. (Japan). Atomic Disease Inst.; Matsuo, Tatsuki; Preston, D.L.; Bennett, J.M.

    1997-12-01

    The Life Span Study (LSS) on 93,741 survivors (fixed cohort) and the Open City Study (OCS) on all survivors (unfixed) irrespective of whether they belonged to LSS or not, have been conducted in parallel over 45 years to ensure reliable case detection. We adopted the FAB classification for acute leukemias and for exposure dose of individual survivors, the new dosimetry system 1986 (DS86). In LSS, 221 leukemia cases were analysed. There was strong evidence of radiation-induced risks for acute myeloid leukemia (AML), acute lymphoid leukemia (ALL) and chronic myeloid leukemia (CML), but not for adult T-cell leukemia and chronic lymphocytic leukemia. There was also significant difference between three major types with respect to the effects of age at bombing and sex, and in the temporal pattern of the elevated risks. For AML the dose response function was non-linear, whereas there was no evidence against linearity for ALL and CML. The hypothesis of a 0.5 Gy threshold could be rejected for three major types of leukemia. Excess Absolute Risk (EAR) estimates in cases per 10,000 Person Year Sievert (PYSv) were 0.6, 1.1, 0.9 for ALL, AML and CML, respectively. The corresponding relative risk at 1.0 Sv were 9.1, 3.3, 6.2, respectively. Although childhood exposure <15 age at bombing apparently induced three major types, the age-related highest risk was observed for ALL. In OCS, 413 cases with DS86 estimates were used for analysis. Type specific incidence rates were calculated indirectly by using the over all incidence of leukemia from LSS data and multiplying these values by the corresponding proportions of cases in OCS. In conjunction with LSS data, the effects of radiation were significantly greater on the incidences of ALL and CML than on that of AML. In the high dose group there was a strong evidence for shorter incubation time and faster decline of elevated risk for ALL and CML than for AML. AML risk was apparently persistent through 1980. (K.H.)

  13. The effect of long term administration of ascorbic acid on the learning and memory deficits induced by diabetes in rat

    Directory of Open Access Journals (Sweden)

    Parisa Hasanein

    2010-04-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Ascorbic acid improves cognitive impairments in several experimental models. Diabetes causes learning and memory deficits. In this study we hypothesized that chronic treatment with ascorbic acid (100mg/kg, p.o would affect on the passive avoidance learning (PAL and memory in control and streptozocin-induced diabetic rats."n"nMethods: Diabetes was induced by a single i.p. injection of STZ (60mg/kg. The rats were considered diabetic if plasma glucose levels exceeded 250mg/dl on three days after STZ injection. Treatment was begun at the onset of hyperglycemia. PAL was assessed 30 days later. Retention test was done 24 h after training. At the end, animals were weighted and blood samples were drawn for plasma glucose measurement."n"nResults: Diabetes caused impairment in acquisition and retrieval processes of PAL and memory in rats. Ascorbic acid treatment improved learning and memory in control rats and reversed learning and memory deficits in diabetic rats. Ascorbic acid administration also improved the body weight loss and hyperglycemia of diabetics. Hypoglycemic and antioxidant properties of the vitamin may be involved in the memory improving effects of such treatment."n"nConclusion: These results show that

  14. Long-term Outcomes of Amniotic Membrane Transplantation in Contact Lens-Induced Pseudomonas Keratitis with Impending Corneal Perforation

    Science.gov (United States)

    Mohammadpour, Mehrdad; Sabet, Fatemeh Alsadat

    2016-01-01

    Purpose: To report the anatomical and visual outcomes of double layered amniotic membrane transplantation (AMT) in eyes with advanced Pseudomonas keratitis leading to Descemetocele formation. Methods: This prospective interventional case series included 6 eyes of 6 female patients with pseudomonas keratitis caused by contact lens-induced infection who underwent double layered AMT. Surgery was performed after the ulcers were found to be poorly responsive to antibiotics, and severe thinning or Descemetocele had developed. All patients underwent a complete examination pre- and postoperatively, as well as anterior segment optical coherence tomography (OCT) and pachymetry or Orbscan after the procedure. Results: Mean follow-up period was 24 months. There was neither frank corneal perforation nor a need for emergent corneal transplantation in any of the eyes. All patients had visual acuity of hand motions before the procedure which improved to 20/50 to 20/30 three months after surgery. No surgical or postoperative complication occurred in this series. Conclusion: Double layered AMT may result in acceptable anatomical outcomes in patients with advanced Pseudomonas keratitis with Descemetocele formation and can eliminate the need for emergent corneal transplantation. PMID:27195083

  15. Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory

    KAUST Repository

    Tadi, Monika

    2015-10-29

    We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte)-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA) paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

  16. Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory.

    Directory of Open Access Journals (Sweden)

    Monika Tadi

    Full Text Available We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4, alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

  17. Long-term Hg pollution-induced structural shifts of bacterial community in the terrestrial isopod (Porcellio scaber) gut

    Energy Technology Data Exchange (ETDEWEB)

    Lapanje, Ales, E-mail: ales@ifb.s [Institute of Physical Biology, Ljubljana (Slovenia); Zrimec, Alexis [Institute of Physical Biology, Ljubljana (Slovenia); Drobne, Damjana [Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana (Slovenia); Rupnik, Maja [Institute of Public Health Maribor, Maribor (Slovenia)

    2010-10-15

    In previous studies we detected lower species richness and lower Hg sensitivity of the bacteria present in egested guts of Porcellio scaber (Crustacea, Isopoda) from chronically Hg polluted than from unpolluted environment. Basis for such results were further investigated by sequencing of 16S rRNA genes of mercury-resistant (Hg{sup r}) isolates and clone libraries. We observed up to 385 times higher numbers of Hg{sup r} bacteria in guts of animals from polluted than from unpolluted environment. The majority of Hg{sup r} strains contained merA genes. Sequencing of 16S rRNA clones from egested guts of animals from Hg-polluted environments showed elevated number of bacteria from Pseudomonas, Listeria and Bacteroidetes relatives groups. In animals from pristine environment number of bacteria from Achromobacter relatives, Alcaligenes, Paracoccus, Ochrobactrum relatives, Rhizobium/Agrobacterium, Bacillus and Microbacterium groups were elevated. Such bacterial community shifts in guts of animals from Hg-polluted environment could significantly contribute to P. scaber Hg tolerance. - Chronic environmental mercury pollution induces bacterial community shifts and presence of elevated number as well as increased diversity of Hg-resistant bacteria in guts of isopods.

  18. Ageing and long-term smoking affects KL-6 levels in the lung, induced sputum and plasma

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    Horimasu Yasushi

    2011-05-01

    Full Text Available Abstract Background KL-6 is a high-molecular-weight glycoprotein classified as a human MUC1 mucin. It was hypothesized that KL-6 could be detectable in the circulating blood and especially in airway secretions in lung diseases associated with mucus production such as chronic obstructive pulmonary disease (COPD. Additional aims of this study were to investigate whether the levels of KL-6 in plasma and sputum are related to ageing and smoking history. Methods The concentrations of KL-6 in plasma and induced sputum supernatants from young and/or middle aged/elderly non-smokers, smokers and patients with COPD were assayed by ELISA (n = 201. The subjects were classified into five groups according to age, smoking status and presence of COPD. In addition, KL-6 expression in control and diseased lung i.e. samples from patients with COPD (n = 28, were analyzed by immunohistochemistry and digital image analysis. Results The plasma levels of KL-6 increased with age both in non-smokers and smokers. Among middle aged/elderly subjects, plasma KL-6 levels in all smokers regardless of COPD were significantly higher than in non-smokers, whereas sputum levels of KL-6 were significantly higher in COPD compared not only to non-smokers but also to smokers. KL-6 was more prominently expressed in the bronchiolar/alveolar epithelium in COPD than in the control lungs. Plasma and sputum KL-6 levels correlated inversely with obstruction and positively with smoking history and ageing. The linear multiple regression analysis confirmed that age and cigarette smoking had independent effects on plasma KL-6. Conclusions KL-6 increases with ageing and chronic smoking history, but prospective studies will be needed to elucidate the significance of KL-6 in chronic airway diseases.

  19. Modeling long term Enhanced in situ Biodenitrification and induced heterogeneity in column experiments under different feeding strategies

    Science.gov (United States)

    Rodríguez-Escales, Paula; Folch, Albert; van Breukelen, Boris M.; Vidal-Gavilan, Georgina; Sanchez-Vila, Xavier

    2016-07-01

    Enhanced In situ Biodenitrification (EIB) is a capable technology for nitrate removal in subsurface water resources. Optimizing the performance of EIB implies devising an appropriate feeding strategy involving two design parameters: carbon injection frequency and C:N ratio of the organic substrate nitrate mixture. Here we model data on the spatial and temporal evolution of nitrate (up to 1.2 mM), organic carbon (ethanol), and biomass measured during a 342 day-long laboratory column experiment (published in Vidal-Gavilan et al., 2014). Effective porosity was 3% lower and dispersivity had a sevenfold increase at the end of the experiment as compared to those at the beginning. These changes in transport parameters were attributed to the development of a biofilm. A reactive transport model explored the EIB performance in response to daily and weekly feeding strategies. The latter resulted in significant temporal variation in nitrate and ethanol concentrations at the outlet of the column. On the contrary, a daily feeding strategy resulted in quite stable and low concentrations at the outlet and complete denitrification. At intermediate times (six months of experiment), it was possible to reduce the carbon load and consequently the C:N ratio (from 2.5 to 1), partly because biomass decay acted as endogenous carbon to respiration, keeping the denitrification rates, and partly due to the induced dispersivity caused by the well-developed biofilm, resulting in enhancement of mixing between the ethanol and nitrate and the corresponding improvement of denitrification rates. The inclusion of a dual-domain model improved the fit at the last days of the experiment as well as in the tracer test performed at day 342, demonstrating a potential transition to anomalous transport that may be caused by the development of biofilm. This modeling work is a step forward to devising optimal injection conditions and substrate rates to enhance EIB performance by minimizing the overall supply of

  20. Long-term effects of febrile convulsion on seizure susceptibility in P77PMC rat--resistant to acoustic stimuli but susceptible to kainate-induced seizures.

    Science.gov (United States)

    Zhao, D Y; Wu, X R; Pei, Y Q; Zuo, Q H

    1985-06-01

    A new audiogenic seizure (AGS)-susceptible strain of rats (P77PMC) was evaluated as a possible model of human febrile seizures. The long-term effects of experimental febrile seizures were observed. All 30-day-old rat pups exhibited clonic seizures during exposure to an ambient temperature of 45 +/- 0.5 degree C. The mean latency from the beginning of the hyperthermic stimulus to the onset of convulsion was 16.9 +/- 2.2 min. The rats survived this hyperthermic seizure, developed a resistance to acoustic stimulations, but were more susceptible at the age of 50 to 60 days to kainate-induced limbic seizures than controls. The results of this study imply that febrile seizures of developing P77PMC rats can change later seizure susceptibility, and there may be some correlation between febrile convulsion and temporal lobe epilepsy. PMID:3996515

  1. Sleep facilitates long-term face adaptation

    OpenAIRE

    Ditye, T.; A.H Javadi; Carbon, C.C.; Walsh, V

    2013-01-01

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted imag...

  2. The GABAA receptor agonist muscimol induces an age- and region-dependent form of long-term depression in the mouse striatum.

    Science.gov (United States)

    Zhang, Xiaoqun; Yao, Ning; Chergui, Karima

    2016-09-01

    Several forms of long-term depression (LTD) of glutamatergic synaptic transmission have been identified in the dorsal striatum and in the nucleus accumbens (NAc). Such experience-dependent synaptic plasticity might play important roles in reward-related learning. The GABAA receptor agonist muscimol was recently found to trigger a long-lasting depression of glutamatergic synaptic transmission in the NAc of adolescent mice, but the mechanisms that underlie this novel form of LTD were not studied. Here we examined the effect of muscimol applied in the perfusion solution on the amplitude of field excitatory postsynaptic potentials/population spikes (fEPSP/PSs) in mouse brain slices. We found that muscimol depressed the fEPSP/PS in the NAc of adolescent mice but not adult mice, through both postsynaptic and presynaptic mechanisms. Indeed, muscimol altered the fEPSP/PS paired-pulse ratio, depolarized the membrane of projection neurons, and decreased the frequency, but not amplitude, of spontaneous excitatory postsynaptic currents in the NAc of adolescent mice. The LTD induced by muscimol likely involved endocannabinoids, metabotropic glutamate receptors (mGluRs), but not TRPV1 receptors. Muscimol-LTD was occluded by prior induction of LTD through low-frequency stimulation (LFS) of the slice, demonstrating a common pathway in the induction of LFS-LTD and muscimol-LTD. We also found that muscimol induced a form of LTD in the dorsolateral striatum of adult but not adolescent mice. This LTD was mediated by endocannabinoids but did not involve mGluRs or TRPV1 receptors. These results identify a novel form of synaptic plasticity, and its mechanisms of induction, which is age and region dependent. These findings may contribute to a better understanding of the increased susceptibility of the adolescent brain to long-term synaptic changes in regions associated with reward mechanisms. PMID:27531838

  3. Estradiol attenuates ischemia-induced death of hippocampal neurons and enhances synaptic transmission in aged, long-term hormone-deprived female rats.

    Directory of Open Access Journals (Sweden)

    Tomoko Inagaki

    Full Text Available BACKGROUND: Transient global forebrain ischemia causes selective, delayed death of hippocampal CA1 pyramidal neurons, and the ovarian hormone 17β-estradiol (E2 reduces neuronal loss in young and middle-aged females. The neuroprotective efficacy of E2 after a prolonged period of hormone deprivation is controversial, and few studies examine this issue in aged animals given E2 treatment after induction of ischemia. METHODOLOGY/PRINCIPAL FINDINGS: The present study investigated the neuroprotective effects of E2 administered immediately after global ischemia in aged female rats (15-18 months after 6 months of hormone deprivation. We also used electrophysiological methods to assess whether CA1 synapses in the aging hippocampus remain responsive to E2 after prolonged hormone withdrawal. Animals were ovariohysterectomized and underwent 10 min global ischemia 6 months later. A single dose of E2 (2.25 µg infused intraventricularly after reperfusion significantly increased cell survival, with 45% of CA1 neurons surviving vs 15% in controls. Ischemia also induced moderate loss of CA3/CA4 pyramidal cells. Bath application of 1 nM E2 onto brain slices derived from non-ischemic aged females after 6 months of hormone withdrawal significantly enhanced excitatory transmission at CA1 synapses evoked by Schaffer collateral stimulation, and normal long-term potentiation (LTP was induced. The magnitude of LTP and of E2 enhancement of field excitatory postsynaptic potentials was indistinguishable from that recorded in slices from young rats. CONCLUSIONS/SIGNIFICANCE: The data demonstrate that 1 acute post-ischemic infusion of E2 into the brain ventricles is neuroprotective in aged rats after 6 months of hormone deprivation; and 2 E2 enhances synaptic transmission in CA1 pyramidal neurons of aged long-term hormone deprived females. These findings provide evidence that the aging hippocampus remains responsive to E2 administered either in vivo or in vitro even after

  4. Protein Synthesis Inhibitors Did Not Interfere with Long-Term Depression Induced either Electrically in Juvenile Rats or Chemically in Middle-Aged Rats.

    Science.gov (United States)

    Abbas, Abdul-Karim

    2016-01-01

    In testing the hypothesis that long-term potentiation (LTP) maintenance depends on triggered protein synthesis, we found no effect of protein synthesis inhibitors (PSIs) on LTP stabilization. Similarly, some studies reported a lack of effect of PSIs on long-term depression (LTD); the lack of effect on LTD has been suggested to be resulting from the short time recordings. If this proposal were true, LTD might exhibit sensitivity to PSIs when the recording intervals were enough long. We firstly induced LTD by a standard protocol involving low frequency stimulation, which is suitable for eliciting NMDAR-LTD in CA1 area of hippocampal slices obtained from juvenile Sprague-Dawley rats. This LTD was persistent for intervals in range of 8-10 h. Treating slices with anisomycin, however, did not interfere with the magnitude and persistence of this form of LTD. The failure of anisomycin to block synaptic-LTD might be relied on the age of animal, the type of protein synthesis inhibitors and/or the inducing protocol. To verify whether those variables altogether were determinant, NMDA or DHPG was used to chemically elicit LTD recorded up to 10 h on hippocampal slices obtained from middle-aged rats. In either form of LTD, cycloheximide did not interfere with LTD stabilization. Furthermore, DHPG application did show an increase in the global protein synthesis as assayed by radiolabeled methodology indicating that though triggered protein synthesis can occur but not necessarily required for LTD expression. The findings confirm that stabilized LTD in either juvenile, or middle-aged rats can be independent of triggered protein synthesis. Although the processes responsible for the independence of LTD stabilization on the triggered protein synthesis are not yet defined, these findings raise the possibility that de novo protein synthesis is not universally necessary. PMID:27517693

  5. A single dose of S-ketamine induces long-term antidepressant effects and decreases oxidative stress in adulthood rats following maternal deprivation.

    Science.gov (United States)

    Réus, Gislaine Z; Carlessi, Anelise S; Titus, Stephanie E; Abelaira, Helena M; Ignácio, Zuleide M; da Luz, Jaine R; Matias, Beatriz I; Bruchchen, Livia; Florentino, Drielly; Vieira, Andriele; Petronilho, Fabricia; Quevedo, João

    2015-11-01

    Ketamine, an antagonist of N-methyl-d-aspartate receptors, has produced rapid antidepressant effects in patients with depression, as well as in animal models. However, the extent and duration of the antidepressant effect over longer periods of time has not been considered. This study evaluated the effects of single dose of ketamine on behavior and oxidative stress, which is related to depression, in the brains of adult rats subjected to maternal deprivation. Deprived and nondeprived Wistar rats were divided into four groups nondeprived+saline; nondeprived+S-ketamine (15 mg/kg); deprived+saline; deprived+S-ketamine (15 mg/kg). A single dose of ketamine or saline was administrated during the adult phase, and 14 days later depressive-like behavior was assessed. In addition, lipid damage, protein damage, and antioxidant enzyme activities were evaluated in the rat brain. Maternal deprivation induces a depressive-like behavior, as verified by an increase in immobility and anhedonic behavior. However, a single dose of ketamine was able to reverse these alterations, showing long-term antidepressant effects. The brains of maternally deprived rats had an increase in protein oxidative damage and lipid peroxidation, but administration of a single dose of ketamine reversed this damage. The activities of antioxidant enzymes superoxide dismutase and catalase were reduced in the deprived rat brains. However, ketamine was also able to reverse these changes. In conclusion, these findings indicate that a single dose of ketamine is able to induce long-term antidepressant effects and protect against neural damage caused by oxidative stress in adulthood rats following maternal deprivation. PMID:25728399

  6. Respiratory syncytial virus-like nanoparticle vaccination induces long-term protection without pulmonary disease by modulating cytokines and T-cells partially through alveolar macrophages

    Directory of Open Access Journals (Sweden)

    Lee YT

    2015-07-01

    Full Text Available Young-Tae Lee,1,* Eun-Ju Ko,1,2,* Hye Suk Hwang,1,2 Jong Seok Lee,1,3 Ki-Hye Kim,1 Young-Man Kwon,1 Sang-Moo Kang1,2 1Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, 2Department of Biology, Georgia State University, Atlanta, GA, USA; 3National Institute of Biological Resources, Incheon, South Korea *These authors contributed equally to this work Abstract: The mechanisms of protection against respiratory syncytial virus (RSV are poorly understood. Virus-like nanoparticles expressing RSV glycoproteins (eg, a combination of fusion and glycoprotein virus-like nanoparticles [FG VLPs] have been suggested to be a promising RSV vaccine candidate. To understand the roles of alveolar macrophages (AMs in inducing long-term protection, mice that were 12 months earlier vaccinated with formalin-inactivated RSV (FI-RSV or FG VLPs were treated with clodronate liposome prior to RSV infection. FI-RSV immune mice with clodronate liposome treatment showed increases in eosinophils, plasmacytoid dendritic cells, interleukin (IL-4+ T-cell infiltration, proinflammatory cytokines, chemokines, and, in particular, mucus production upon RSV infection. In contrast to FI-RSV immune mice with severe pulmonary histopathology, FG VLP immune mice showed no overt sign of histopathology and significantly lower levels of eosinophils, T-cell infiltration, and inflammatory cytokines, but higher levels of interferon-γ, which are correlated with protection against RSV disease. FG VLP immune mice with depletion of AMs showed increases in inflammatory cytokines and chemokines, as well as eosinophils. The results in this study suggest that FG nanoparticle vaccination induces long-term protection against RSV and that AMs play a role in the RSV protection by modulating eosinophilia, mucus production, inflammatory cytokines, and T-cell infiltration. Keywords: alveolar macrophage, nanoparticle vaccine, VLP, FI-RSV, RSV disease

  7. Long-term administration of a small molecular weight catalytic metalloporphyrin antioxidant, AEOL 10150, protects lungs from radiation-induced injury

    International Nuclear Information System (INIS)

    Purpose: To determine whether administration of a catalytic antioxidant, Mn(III) tetrakis(N,N'-diethylimidazolium-2-yl) porphyrin, AEOL 10150, with superoxide dismutase (SOD) mimetic properties, reduces the severity of radiation-induced injury to the lung from single-dose irradiation (RT) of 28 Gy. Methods and Materials: Rats were randomly divided into four different dose groups (0, 1, 10, and 30 mg/kg/day of AEOL 10150), receiving either short-term (1 week) or long-term (10 weeks) drug administration via osmotic pumps. Rats received single-dose irradiation (RT) of 28 Gy to the right hemithorax. Breathing rates, body weights, blood samples, histopathology, and immunohistochemistry were used to assess lung damage. Results: There was no significant difference in any of the study endpoints between the irradiated controls and the three groups receiving RT and short-term administration of AEOL 10150. For the long-term administration, functional determinants of lung damage 20 weeks postradiation were significantly worse for RT + phosphate-buffered saline (PBS) and RT + 1 mg/kg/day of AEOL 10150 as compared with the irradiated groups treated with higher doses of AEOL 10150 (10 or 30 mg/kg/day). Lung histology at 20 weeks revealed a significant decrease in structural damage and collagen deposition in rats receiving 10 or 30 mg/kg/day after radiation in comparison to the RT + PBS and 1 mg/kg/day groups. Immunohistochemistry demonstrated a significant reduction in macrophage accumulation, oxidative stress, and hypoxia in rats receiving AEOL 10150 (10 or 30 mg/kg/day) after lung irradiation compared with the RT + PBS and 1 mg/kg/day groups. Conclusions: The chronic administration of a novel catalytic antioxidant, AEOL 10150, demonstrates a significant protective effect from radiation-induced lung injury. AEOL 10150 has its primary impact on the cascade of events after irradiation, and adding the drug before irradiation and its short-term administration have no significant

  8. Blockade of KCa3.1 potassium channels protects against cisplatin-induced acute kidney injury.

    Science.gov (United States)

    Chen, Cheng-Lung; Liao, Jiunn-Wang; Hu, Oliver Yoa-Pu; Pao, Li-Heng

    2016-09-01

    Tubular cell apoptosis significantly contributes to cisplatin-induced acute kidney injury (AKI) pathogenesis. Although KCa3.1, a calcium-activated potassium channel, participates in apoptosis, its involvement in cisplatin-induced AKI is unknown. Here, we found that cisplatin treatment triggered an early induction of KCa3.1 expression associated with HK-2 cell apoptosis, the development of renal tubular damage, and apoptosis in mice. Treatment with the highly selective KCa3.1 blocker TRAM-34 suppressed cisplatin-induced HK-2 cell apoptosis. We further assessed whether KCa3.1 mediated cisplatin-induced AKI in genetic knockout and pharmacological blockade mouse models. KCa3.1 deficiency reduced renal function loss, renal tubular damage, and the induction of the apoptotic marker caspase-3 in the kidneys of cisplatin-treated KCa3.1 (-/-) mice. Pharmacological blockade of KCa3.1 by TRAM-34 similarly attenuated cisplatin-induced AKI in mice. Furthermore, we dissected the mechanisms underlying cisplatin-induced apoptosis reduction via KCa3.1 blockade. We found that KCa3.1 blockade attenuated cytochrome c release and the increase in the intrinsic apoptotic mediators Bax, Bak, and caspase-9 after cisplatin treatment. KCa3.1 blocking inhibited the cisplatin-induced activation of the endoplasmic reticulum (ER) stress mediator caspase-12, which is independent of calcium-dependent protease m-calpain activation. Taken together, KCa3.1 blockade protects against cisplatin-induced AKI through the attenuation of apoptosis by interference with intrinsic apoptotic and ER stress-related mediators, providing a potential target for the prevention of cisplatin-induced AKI. PMID:26438401

  9. Levothyroxine rescues the lead-induced hypothyroidism and impairment of long-term potentiation in hippocampal CA1 region of the developmental rats

    International Nuclear Information System (INIS)

    Lead (Pb) exposure during development has been associated with impaired long-term potentiation (LTP). Hypothyroidism happening upon subjects with occupational exposure to Pb is suggestive of an adverse effect of Pb on thyroid homeostasis, leading to the hypothesis that Pb exposure may alter thyroid hormone homeostasis. Hippocampus is one of the targets of Pb exposure, and is sensitive to and dependent on thyroid hormones, leading us to explore whether levothyroxine (L-T4) administration could alter the thyroid disequilibrium and impairment of LTP in rat hippocampus caused by Pb exposure. Our results show that Pb exposure caused a decrease in triiodothyronine (T3) and tetraiodothyronine (T4) levels accompanied by a dramatic decrease of TSH and application of L-T4 restored these changes to about control levels. Hippocampal and blood Pb concentration were significantly reduced following L-T4 treatment. L-T4 treatment rescued the impairment of LTP induced by the Pb exposure. These results suggest that Pb exposure may lead to thyroid dysfunction and induce hypothyroidism and provide a direct electrophysiological proof that L-T4 relieves chronic Pb exposure-induced impairment of synaptic plasticity. - Highlights: → Lead may interfere with thyroid hormone homeostasis and induce hypothyroidism. → Levothyroxine decreases the hippocampal and blood Pb concentration. → Levothyroxine amends the T3, T4 and TSH levels in blood. → Levothyroxine rescues the impaired LTP in CA1.

  10. Long-term exposure to depleted uranium in Gulf-War veterans does not induce chromosome aberrations in peripheral blood lymphocytes.

    Science.gov (United States)

    Bakhmutsky, Marina V; Squibb, Katherine; McDiarmid, Melissa; Oliver, Marc; Tucker, James D

    2013-10-01

    Depleted uranium (DU) is a high-density heavy metal that has been used in munitions since the 1991 Gulf War. DU is weakly radioactive and chemically toxic, and long-term exposure may cause adverse health effects. This study evaluates genotoxic effects of exposure to DU by measuring chromosome damage in peripheral blood lymphocytes with fluorescence in situ hybridization whole-chromosome painting. Study participants are Gulf War-I Veterans with embedded DU fragments and/or inhalation exposure due to involvement in friendly-fire incidents; they are enrolled in a long-term health surveillance program at the Baltimore Veterans Administration Medical Center. Blood was drawn from 35 exposed male veterans aged 39 to 62 years. Chromosomes 1, 2, and 4 were painted red and chromosomes 3, 5, and 6 were simultaneously labeled green. At least 1800 metaphase cells per subject were scored. Univariate regression analyses were performed to evaluate the effects of log(urine uranium), age at time of blood draw, log(lifetime X-rays), pack-years smoked and alcohol use, against frequencies of cells with translocated chromosomes, dicentrics, acentric fragments, color junctions and abnormal cells. No significant relationships were observed between any cytogenetic endpoint and log(urine uranium) levels, smoking, or log(lifetime X-rays). Age at the time of blood draw showed significant relationships with all endpoints except for cells with acentric fragments. Translocation frequencies in these Veterans were all well within the normal range of published values for healthy control subjects from around the world. These results indicate that chronic exposure to DU does not induce significant levels of chromosome damage in these Veterans. PMID:23933231

  11. Helicobacter pylori induced gastric immunopathology is associated with distinct microbiota changes in the large intestines of long-term infected Mongolian gerbils.

    Directory of Open Access Journals (Sweden)

    Markus M Heimesaat

    Full Text Available BACKGROUND: Gastrointestinal (GI inflammation in mice and men are frequently accompanied by distinct changes of the GI microbiota composition at sites of inflammation. Helicobacter (H. pylori infection results in gastric immunopathology accompanied by colonization of stomachs with bacterial species, which are usually restricted to the lower intestine. Potential microbiota shifts distal to the inflammatory process following long-term H. pylori infection, however, have not been studied so far. METHODOLOGY/PRINCIPAL FINDINGS: For the first time, we investigated microbiota changes along the entire GI tract of Mongolian gerbils after 14 months of infection with H. pylori B8 wildtype (WT or its isogenic ΔcagY mutant (MUT strain which is defective in the type IV secretion system and thus unable to modulate specific host pathways. Comprehensive cultural analyses revealed that severe gastric diseases such as atrophic pangastritis and precancerous transformations were accompanied by elevated luminal loads of E. coli and enterococci in the caecum and together with Bacteroides/Prevotella spp. in the colon of H. pylori WT, but not MUT infected gerbils as compared to naïve animals. Strikingly, molecular analyses revealed that Akkermansia, an uncultivable species involved in mucus degradation, was exclusively abundant in large intestines of H. pylori WT, but not MUT infected nor naïve gerbils. CONCLUSION/SIGNIFICANCE: Taken together, long-term infection of Mongolian gerbils with a H. pylori WT strain displaying an intact type IV secretion system leads to distinct shifts of the microbiota composition in the distal uninflamed, but not proximal inflamed GI tract. Hence, H. pylori induced immunopathogenesis of the stomach, including hypochlorhydria and hypergastrinemia, might trigger large intestinal microbiota changes whereas the exact underlying mechanisms need to be further unraveled.

  12. Long-term effects of ionizing radiation

    International Nuclear Information System (INIS)

    This paper approaches the long-term effects of ionizing radiation considering the common thought that killing of cells is the basis for deterministic effects and that the subtle changes in genetic information are important in the development of radiation-induced cancer, or genetic effects if these changes are induced in germ cells

  13. Involvement of microglia and interleukin-18 in the induction of long-term potentiation of spinal nociceptive responses induced by tetanic sciatic stimulation

    Institute of Scientific and Technical Information of China (English)

    Yu-Xia Chu; Yu-Qiu Zhang; Zhi-Qi Zhao

    2012-01-01

    Objective The present study aimed to investigate the potential roles of spinal microglia and downstream molecules in the induction of spinal long-term potentiation (LTP) and mechanical allodynia by tetanic stimulation of the sciatic nerve (TSS).Methods Spinal LTP was induced in adult male Sprague-Dawley rats by tetanic stimulation of the sciatic nerve (0.5 ms,100 Hz,40 V,10 trains of 2-s duration at 10-s intervals).Mechanical allodynia was determined using von Frey hairs.Immunohistochemical staining and Westem blot were used to detect changes in glial expression of interleukin- 18 (IL- 18) and IL- 18 receptor (IL- 18R).Results TSS induced LTP of C-fiber-evoked field potentials in the spinal cord.Intrathecal administration of the microglial inhibitor minocycline (200 μg/20 μL) 1 h before TSS completely blocked the induction of spinal LTP.Furthermore,after intrathecal injection of minocycline (200 μg/20 μL) by lumbar puncture 1 h before TSS,administration of minocycline for 7 consecutive days (once per day) partly inhibited bilateral allodynia.Immunohistochemistry showed that minocycline inhibited the sequential activation of microglia and astrocytes,and IL-1 8 was predominantly colocalized with the microglial marker Iba-1 in the spinal superficial dorsal horn.Western blot revealed that repeated intrathecal injection of minocycline significantly inhibited the increased expression of IL-18 and IL-18Rs in microglia induced by TSS.Conclusion The IL-18 signaling pathway in microglia is involved in TSS-induced spinal LTP and mechanical allodynia.

  14. 人工流产对妇女长期心理健康的影响%The influence of induced abortion in women's long-term mental health

    Institute of Scientific and Technical Information of China (English)

    史春; 姜芬; 郭洪花

    2015-01-01

    Objective To discuss the influence of induced abortion in women 's long -term mental health. Methods 251 women experienced induced abortion ( induced abortion group ) and 250 healthy women of childbearing age ( control group ) were randomly selected from 3 tertiary hospitals from June 2012 to October 2012 in Haikou. Using the post traumatic stress disorder( PTSD) Checklist-Civilian Version ( PCL -C) Scale, cases in induced abortion group 10 days post -operation and control group in the corresponding period, cases in induced abortion group 3, 6, 12, 24 months post-operation were surveyed. Results The total scores of PCL-C and the scores of subscales re-experience, avoidance and hyper-arousal in induced abortion group were higher than that in control group(P0. 05), and then the downward trend was emerged after 6,12,24 months post-operation. The trend of re-experience and hyper-arousal scores declined. The avoidance scores rose at the beginning at the third month, then declined. Conclusion Induced abortion causes the long-term influence on women's mental health as a kind of traumatic stressors.%目的 探讨人工流产对妇女长期心理健康的影响. 方法 采用随机数字表法随机抽取2012年6~10月海口市3所三级医院的251名人工流产妇女(人工流产组)及250名健康育龄期妇女(对照组),运用创伤后应激障碍(post traumatic stress disorder,PTSD)自评量表(PCL-C),对人工流产组术后第10天及同期对照组,人工流产组术后第3、6、12、24个月进行调查,并进行对比分析. 结果 人工流产组妇女术后第10天PCL-C的总分、再体验、回避及警觉得分均显著高于对照组(P0. 05),第6、12、24个月呈现显著下降趋势;再体验和警觉维度呈下降趋势;回避维度变化最初为上升趋势,第3个月达高峰,之后呈明显下降趋势. 结论 人工流产作为一种创伤应激源对术后妇女的心理健康具有长期影响.

  15. Long-term environmental stewardship.

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Michael David

    2010-08-01

    The purpose of this Supplemental Information Source Document is to effectively describe Long-Term Environmental Stewardship (LTES) at Sandia National Laboratories/New Mexico (SNL/NM). More specifically, this document describes the LTES and Long-Term Stewardship (LTS) Programs, distinguishes between the LTES and LTS Programs, and summarizes the current status of the Environmental Restoration (ER) Project.

  16. Prenatal stress induces long-term effects in cell turnover in the hippocampus-hypothalamus-pituitary axis in adult male rats.

    Directory of Open Access Journals (Sweden)

    Eva Baquedano

    Full Text Available Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day. Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations.

  17. Prenatal Stress Induces Long-Term Effects in Cell Turnover in the Hippocampus-Hypothalamus-Pituitary Axis in Adult Male Rats

    Science.gov (United States)

    Baquedano, Eva; García-Cáceres, Cristina; Diz-Chaves, Yolanda; Lagunas, Natalia; Calmarza-Font, Isabel; Azcoitia, Iñigo; Garcia-Segura, Luis M.; Argente, Jesús; Chowen, Julie A.; Frago, Laura M.

    2011-01-01

    Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations. PMID:22096592

  18. Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm Brain Injury

    Science.gov (United States)

    Sifringer, Marco; van de Looij, Yohan; Herz, Josephine; Sizonenko, Stéphane V.; Kempe, Karina; Palasz, Joanna; Hadamitzky, Martin; Fandrey, Joachim

    2016-01-01

    Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg) at the onset of hyperoxia (24 hours, 80% oxygen) in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity. PMID:27493706

  19. Survival or revival: long-term preservation induces a reversible viable but non-culturable state in methane-oxidizing bacteria.

    Directory of Open Access Journals (Sweden)

    Sven Hoefman

    Full Text Available Knowledge on long-term preservation of micro-organisms is limited and research in the field is scarce despite its importance for microbial biodiversity and biotechnological innovation. Preservation of fastidious organisms such as methane-oxidizing bacteria (MOB has proven difficult. Most MOB do not survive lyophilization and only some can be cryopreserved successfully for short periods. A large-scale study was designed for a diverse set of MOB applying fifteen cryopreservation or lyophilization conditions. After three, six and twelve months of preservation, the viability (via live-dead flow cytometry and culturability (via most-probable number analysis and plating of the cells were assessed. All strains could be cryopreserved without a significant loss in culturability using 1% trehalose in 10-fold diluted TSB (TT as preservation medium and 5% DMSO as cryoprotectant. Several other cryopreservation and lyophilization conditions, all of which involved the use of TT medium, also allowed successful preservation but showed a considerable loss in culturability. We demonstrate here that most of these non-culturables survived preservation according to viability assessment indicating that preservation induces a viable but non-culturable (VBNC state in a significant fraction of cells. Since this state is reversible, these findings have major implications shifting the emphasis from survival to revival of cells in a preservation protocol. We showed that MOB cells could be significantly resuscitated from the VBNC state using the TT preservation medium.

  20. Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm Brain Injury

    Directory of Open Access Journals (Sweden)

    Daniela Hoeber

    2016-01-01

    Full Text Available Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg at the onset of hyperoxia (24 hours, 80% oxygen in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity.

  1. Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm Brain Injury.

    Science.gov (United States)

    Hoeber, Daniela; Sifringer, Marco; van de Looij, Yohan; Herz, Josephine; Sizonenko, Stéphane V; Kempe, Karina; Serdar, Meray; Palasz, Joanna; Hadamitzky, Martin; Endesfelder, Stefanie; Fandrey, Joachim; Felderhoff-Müser, Ursula; Bendix, Ivo

    2016-01-01

    Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg) at the onset of hyperoxia (24 hours, 80% oxygen) in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity. PMID:27493706

  2. Suspended C60 nanoparticles protect against short-term UV and fluoranthene photo-induced toxicity, but cause long-term cellular damage in Daphnia magna

    International Nuclear Information System (INIS)

    The increased production of nanotechnology materials is a potential source of nano-sized particles (NSPs) in aquatic ecosystems. Meanwhile, polycyclic aromatic hydrocarbons (PAHs), in the presence of ecologically relevant levels of ultraviolet radiation (UV), can be acutely toxic to aquatic species including fish and invertebrates. Considering that suspended carbon-based NSPs (e.g., C60 fullerenes) may act in similar ways as dissolved organic matter (DOM) by altering the bioavailability of PAHs, the objective of this research was to determine the effect of suspended C60 on the photo-induced toxicity of fluoranthene. Transmission electron microscopy indicated that the presence of C60 protected cellular components (e.g., mitochondria, microvilli, and basal infoldings) in organisms exposed to UV and fluoranthene phototoxicity in short-term exposures. However, we found that long-term exposure (21 d) of low-level C60 caused significant cellular damage in the Daphnia magna alimentary canal. This paper highlights the importance of examining the interactions between existing stressors and nanoparticles in the aquatic environment.

  3. The severe complication of Stevens–Johnson syndrome induced by long-term clozapine treatment in a male schizophrenia patient: a case report

    Science.gov (United States)

    Wu, Ming-Kung; Chung, Weilun; Wu, Ching-Kuan; Tseng, Ping-Tao

    2015-01-01

    Introduction: Stevens–Johnson syndrome (SJS) is a severe adverse drug reaction that can result in disability and mortality. SJS is defined as having a widespread distribution throughout the whole body surface area with carbamazepine, have been reported to have a greater correlation to SJS. Although clozapine use has been mentioned as a risk factor for development of SJS, no report has clearly described the features of SJS as a reaction to clozapine use. Herein, we report the case of a patient presenting SJS after long-term clozapine treatment. Case report: Mr A was a 54-year-old male with a diagnosis of chronic schizophrenia. He was hospitalized in a mental institute and received clozapine 200 mg/day for 2 years, without discomfort or drug side effects. He developed acute-onset mouth edema, multiple oral and ocular ulcers, oral and ocular mucosa swelling, and multiple erythematous skin rashes over his entire body and extremities with hypertension and high fever. SJS was diagnosed after referral to a general hospital. Results The SJS subsided under supportive treatment. Conclusion Accumulated lymphocytes and macrophages in the epidermis and elevated TNF-α might cause an immune reaction and apoptosis and result in the clinical presentation of SJS. Clozapine is believed to modulate the immunologic reaction, and therefore might induce SJS through immunomodulation. This case highlights the importance of considering the possibility of SJS resulting from the use of drugs for which there are no reports of such a severe complication. PMID:25914536

  4. Slow oscillations in two pairs of dopaminergic neurons gate long-term memory formation in Drosophila.

    Science.gov (United States)

    Plaçais, Pierre-Yves; Trannoy, Séverine; Isabel, Guillaume; Aso, Yoshinori; Siwanowicz, Igor; Belliart-Guérin, Ghislain; Vernier, Philippe; Birman, Serge; Tanimoto, Hiromu; Preat, Thomas

    2012-04-01

    A fundamental duty of any efficient memory system is to prevent long-lasting storage of poorly relevant information. However, little is known about dedicated mechanisms that appropriately trigger production of long-term memory (LTM). We examined the role of Drosophila dopaminergic neurons in the control of LTM formation and found that they act as a switch between two exclusive consolidation pathways leading to LTM or anesthesia-resistant memory (ARM). Blockade, after aversive olfactory conditioning, of three pairs of dopaminergic neurons projecting on mushroom bodies, the olfactory memory center, enhanced ARM, whereas their overactivation conversely impaired ARM. Notably, blockade of these neurons during the intertrial intervals of a spaced training precluded LTM formation. Two pairs of these dopaminergic neurons displayed sustained calcium oscillations in naive flies. Oscillations were weakened by ARM-inducing massed training and were enhanced during LTM formation. Our results indicate that oscillations of two pairs of dopaminergic neurons control ARM levels and gate LTM. PMID:22366756

  5. Blockade of store-operated calcium entry alleviates ethanol-induced hepatotoxicity via inhibiting apoptosis

    International Nuclear Information System (INIS)

    Extracellular Ca2+ influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca2+ entry (SOCE) was involved in liver injury induced by ethanol in HepG2 cells. However, the mechanisms underlying liver injury caused by SOCE remain unclear. We aimed to investigate the effects and mechanism of SOCE inhibition on liver injury induced by ethanol in BRL cells and Sprague–Dawley rats. Our data demonstrated that ethanol (0–400 mM) dose-dependently increased hepatocyte injury and 100 mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72 h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca2+ overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and inhibited ethanol-induced apoptosis. STIM1 and Orai1 expression was greater in ethanol-treated than control rats, and the SOCE inhibitor corosolic acid ameliorated the histopathological findings and alanine transaminase and aspartate transaminase activity as well as decreased cytochrome C release and inhibited alcohol-induced cell apoptosis. These findings suggest that SOCE blockade could alleviate alcohol-induced hepatotoxicity via inhibiting apoptosis. SOCE might be a useful therapeutic target in alcoholic liver diseases. - Highlights: • Blockade of SOCE alleviated overload of Ca2+ and hepatotoxicity after ethanol application. • Blockade of SOCE inhibited mitochondrial apoptosis after ethanol application. • SOCE might be a useful therapeutic target in alcoholic liver diseases

  6. Blockade of store-operated calcium entry alleviates ethanol-induced hepatotoxicity via inhibiting apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Ruibing [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Lihui [Shandong Normal University, Jinan, Shandong Province 250012 (China); Luo, Zheng; Guo, Xiaolan [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Ming, E-mail: ymylh@163.com [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China)

    2015-08-15

    Extracellular Ca{sup 2+} influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca{sup 2+} entry (SOCE) was involved in liver injury induced by ethanol in HepG2 cells. However, the mechanisms underlying liver injury caused by SOCE remain unclear. We aimed to investigate the effects and mechanism of SOCE inhibition on liver injury induced by ethanol in BRL cells and Sprague–Dawley rats. Our data demonstrated that ethanol (0–400 mM) dose-dependently increased hepatocyte injury and 100 mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72 h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca{sup 2+} overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and inhibited ethanol-induced apoptosis. STIM1 and Orai1 expression was greater in ethanol-treated than control rats, and the SOCE inhibitor corosolic acid ameliorated the histopathological findings and alanine transaminase and aspartate transaminase activity as well as decreased cytochrome C release and inhibited alcohol-induced cell apoptosis. These findings suggest that SOCE blockade could alleviate alcohol-induced hepatotoxicity via inhibiting apoptosis. SOCE might be a useful therapeutic target in alcoholic liver diseases. - Highlights: • Blockade of SOCE alleviated overload of Ca{sup 2+} and hepatotoxicity after ethanol application. • Blockade of SOCE inhibited mitochondrial apoptosis after ethanol application. • SOCE might be a useful therapeutic target in alcoholic liver diseases.

  7. Immediate and Long-Term Outcome of Acute H2S Intoxication Induced Coma in Unanesthetized Rats: Effects of Methylene Blue.

    Directory of Open Access Journals (Sweden)

    Takashi Sonobe

    Full Text Available Acute hydrogen sulfide (H2S poisoning produces a coma, the outcome of which ranges from full recovery to severe neurological deficits. The aim of our study was to 1--describe the immediate and long-term neurological effects following H2S-induced coma in un-anesthetized rats, and 2--determine the potential benefit of methylene blue (MB, a compound we previously found to counteract acute sulfide cardiac toxicity.NaHS was administered IP in un-sedated rats to produce a coma (n = 34. One minute into coma, the rats received MB (4 mg/kg i.v. or saline. The surviving rats were followed clinically and assigned to Morris water maze (MWM and open field testing then sacrificed at day 7.Sixty percent of the non-treated comatose rats died by pulseless electrical activity. Nine percent recovered with neurological deficits requiring euthanasia, their brain examination revealed major neuronal necrosis of the superficial and middle layers of the cerebral cortex and the posterior thalamus, with variable necrosis of the caudate putamen, but no lesions of the hippocampus or the cerebellum, in contrast to the typical distribution of post-ischemic lesions. The remaining animals displayed, on average, a significantly less effective search strategy than the control rats (n = 21 during MWM testing. Meanwhile, 75% of rats that received MB survived and could perform the MWM test (P<0.05 vs non-treated animals. The treated animals displayed a significantly higher occurrence of spatial search than the non-treated animals. However, a similar proportion of cortical necrosis was observed in both groups, with a milder clinical presentation following MB.In conclusion, in rats surviving H2S induced coma, spatial search patterns were used less frequently than in control animals. A small percentage of rats presented necrotic neuronal lesions, which distribution differed from post-ischemic lesions. MB dramatically improved the immediate survival and spatial search strategy in the

  8. Long-term reindeer grazing limits warming-induced increases in CO2 released by tundra heath soil: potential role of soil C quality

    International Nuclear Information System (INIS)

    The current climate warming in the Arctic may increase the microbial degradation of vast pools of soil carbon (C); however, the temperature sensitivity of decomposition is often highly dependent on the quality of accumulated soil C. Grazing by reindeer (Rangifer tarandus L.) substantially affects the dominant vegetation and often increases graminoids in relation to dwarf shrubs in ecosystems, but the effect of this vegetation shift on the soil C quality has not been previously investigated. We analyzed the soil C quality and rate of microbially mediated CO2 release at different temperatures in long-term laboratory incubations using soils from lightly grazed dwarf shrub-dominated and heavily grazed graminoid-dominated tundra ecosystem. The soil C quality was characterized by solid-state cross-polarization magic angle spinning (CPMAS 13C NMR) spectroscopy, which showed a higher relative proportion of carbohydrate C under light grazing and higher relative proportion of aliphatic not-O-substituted C under heavy grazing. Initial measurements showed lower temperature sensitivity of the CO2 release in soils under light grazing compared with soil under heavy grazing, but the overall CO2 release rate and its temperature sensitivity increased under light grazing as the soil incubation progressed. At the end of incubation, significantly more carbohydrate C had been lost in soils under light grazing compared with heavy grazing. These findings indicate that there may be a link between the grazer-induced effects on soil C quality and the potential of soils to release CO2 to atmosphere. We suggest that vegetation shifts induced by grazing could influence the proportion of accumulated soil C that is vulnerable to microbial degradation under warming climate. (letter)

  9. Split-dose atropine versus glycopyrrolate with neostigmine for reversal of gallamine-induced neuromuscular blockade

    DEFF Research Database (Denmark)

    Wetterslev, J; Jarnvig, I; Jørgensen, L N;

    1991-01-01

    The effects of a split-dose of atropine sulphate versus a single dose of glycopyrrolate given with neostigmine for the reversal of gallamine-induced neuromuscular blockade were studied in 55 patients undergoing gynaecological surgery. The patients were randomized to receive either a single dose of......, whereas none occurred in the glycopyrrolate group (P less than 0.05). It is concluded that a split-dose of atropine has similar chronotropic effects to a single dose of glycopyrrolate for the reversal of gallamine-induced neuromuscular blockade. However, the finding of a higher incidence of cardiac...... arrhythmias in the atropine group suggests that this reversal regime should be reserved for patients without cardiac disease....

  10. BLOCKADE OF CENTRAL NICOTINE ACETYLCHOLINE RECEPTOR SIGNALING ATTENUATE GHRELIN-INDUCED FOOD INTAKE IN RODENTS

    OpenAIRE

    S.L. Dickson; Hrabovszky, E; Hansson, C.; Jerlhag, E.; Alvarez-Crespo, M.; Skibicka, K. P.; Molnar, C. S.; Liposits, Z; Engel, J. A.; Egecioglu, E.

    2010-01-01

    Here we sought to determine whether ghrelin's central effects on food intake can be interrupted by nicotinic cholinergic receptor (nAChR) blockade. Ghrelin regulates mesolimbic dopamine neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc), partly via cholinergic VTA afferents originating in the laterodorsal tegmental area (LDTg). Given that these cholinergic projections to the VTA have been implicated in natural as well as drug-induced reinforcement, we sou...

  11. Blockade of N-methyl-d-aspartate receptor activation suppresses learning-induced synaptic elimination

    OpenAIRE

    Bock, Jörg; Braun, Katharina

    1999-01-01

    Auditory filial imprinting in the domestic chicken is accompanied by a dramatic loss of spine synapses in two higher associative forebrain areas, the mediorostral neostriatum/hyperstriatum ventrale (MNH) and the dorsocaudal neostriatum (Ndc). The cellular mechanisms that underlie this learning-induced synaptic reorganization are unclear. We found that local pharmacological blockade of N-methyl-d-aspartate (NMDA) receptors in the MNH, a manipulation that has been shown previously to impair aud...

  12. Long-Term Effects of (–)-Epigallocatechin Gallate (EGCG) on Pristane-Induced Arthritis (PIA) in Female Dark Agouti Rats

    Science.gov (United States)

    Leichsenring, Anna; Bäcker, Ingo; Furtmüller, Paul G.; Obinger, Christian; Lange, Franziska; Flemmig, Jörg

    2016-01-01

    Rheumatoid arthritis (RA)—a widespread chronic inflammatory disease in industrialized countries—is characterized by a persistent and progressive joint destruction. The chronic pro-inflammatory state results from a mutual activation of the innate and the adaptive immune system, while the exact pathogenesis mechanism is still under discussion. New data suggest a role of the innate immune system and especially polymorphonuclear granulocytes (PMNs, neutrophils) not only during onset and the destructive phase of RA but also at the chronification of the disease. Thereby the enzymatic activity of myeloperoxidase (MPO), a peroxidase strongly abundant in neutrophils, may be important: While its peroxidase activity is known to contribute to cartilage destruction at later stages of RA the almost MPO-specific oxidant hypochlorous acid (HOCl) is also discussed for certain anti-inflammatory effects. In this study we used pristane-induced arthritis (PIA) in Dark Agouti rats as a model for the chronic course of RA in man. We were able to shown that a specific detection of the HOCl-producing MPO activity provides a sensitive new marker to evaluate the actual systemic inflammatory status which is only partially detectable by the evaluation of clinical symptoms (joint swelling and redness measurements). Moreover, we evaluated the long-term pharmacological effect of the well-known anti-inflammatory flavonoid epigallocatechin gallate (EGCG). Thereby only upon early and continuous oral application of this polyphenol the arthritic symptoms were considerably diminished both in the acute and in the chronic phase of the disease. The obtained results were comparable to the treatment control (application of methotrexate, MTX). As revealed by stopped-flow kinetic measurements, EGCG may regenerate the HOCl-production of MPO which is known to be impaired at chronic inflammatory diseases like RA. It can be speculated that this MPO activity-promoting effect of EGCG may contribute to the

  13. Effect of enzyme-induced pulmonary emphysema in Syrian hamsters on the deposition and long-term retention of inhaled particles

    International Nuclear Information System (INIS)

    Experimental emphysema was induced in Syrian hamsters by: (a) intratracheal instillation of elastase; or (b) inhalation of paparin aerosols. After 3 wk, treated and control groups were simultaneously exposed to an aerosol of relatively insoluble 137Cs-labeled, heat-treated aluminosilicate particles with an aerodynamic diameter of 1.4 or 1.6 μm. The lung deposition of particles measured 3 hr after inhalation exposure was significantly lower in hamsters exposed to elastase or papain. The mean whole-body retention data for each group were fitted with three-component exponential equations. The first component, which represented early clearance and constituted 78% to 83% of the initial body burden in all groups, occurred rapidly with a half-time of 0.6 to 0.8 days, and probably represented particles deposited in the nasopharynx and ciliated airways. The second component represented an intermediate clearance phase and was much faster in animals with emphysema than in controls. The enzyme treatments resulted in a prolonged half-time in the long-term clearance component. The effect of both enzyme treatments on the retention of particles was similar although the patterns of emphysema produced differed. Elastase instilled intratracheally caused diffuse destruction and enlargement of alveoli with a loss of pulmonary elastic recoil. Papain aerosols caused focal destruction and enlargement of alveoli around terminal bronchioles with no loss of elastic recoil. A common feature was an increased number of alveolar macrophages, which may account for the increased, early clearance of particles. The prolonged retention of a small fraction of particles may be due to focal accumulations of particle-laden macrophages which were prominent in distal alveoli of the papain-exposed hamsters and, to a lesser degree, in the elastase-treated hamsters

  14. Intermittent hypoxia-induced respiratory long-term facilitation is dominated by enhanced burst frequency, not amplitude, in spontaneously breathing urethane-anesthetized neonatal rats.

    Science.gov (United States)

    Reid, Inefta M; Solomon, Irene C

    2014-01-01

    Acute intermittent hypoxia (AIH) triggers a form of respiratory plasticity known as long-term facilitation (LTF), which is manifested as a progressive increase in respiratory motor activity that lasts for minutes to hours after the hypoxic stimulus is removed. Respiratory LTF has been reported in numerous animal models, but it appears to be influenced by a variety of factors (e.g., species, age, and gender). While most studies focusing on respiratory LTF have been conducted in adult (including young adult) rat preparations, little is known about the influence of postnatal maturation on AIH-induced respiratory LTF. To begin to address this issue, we examined diaphragm EMG activity in response to and at 5-min intervals for 60 min following three 5-min episodes of hypoxia (8% O2) in urethane-anesthetized spontaneously breathing P14-P15 neonatal rats (n=15). For these experiments, the hypoxic episodes were separated by hyperoxia (40% O2), and all rats were continuously supplied with ~4% CO2. During the AIH trials, burst frequency was increased by ~20-90% above baseline in each of the rats examined while changes in burst amplitude were highly variable. Following the AIH episodes, respiratory LTF was characterized by predominantly an increase in burst frequency (fLTF) ranging from ~10% to 55%, with most rats exhibiting a 20-40% increase. In seven rats, however, an increase in amplitude (ampLTF) (~10%, n=3; ~20%, n=3; ~30%, n=1) was also noted. These data suggest that in contrast to observations in anesthetized ventilated adult rats, in anesthetized spontaneously breathing P14-P15 neonatal rats, respiratory LTF is dominated by fLTF, not ampLTF. PMID:25194200

  15. The severe complication of Stevens–Johnson syndrome induced by long-term clozapine treatment in a male schizophrenia patient: a case report

    Directory of Open Access Journals (Sweden)

    Wu MK

    2015-04-01

    Full Text Available Ming-Kung Wu,1 Weilun Chung,2 Ching-Kuan Wu,2 Ping-Tao Tseng2 1Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Psychiatry, Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai’s Home, Kaohsiung, Taiwan Introduction: Stevens–Johnson syndrome (SJS is a severe adverse drug reaction that can result in disability and mortality. SJS is defined as having a widespread distribution throughout the whole body surface area with <10% extent of skin detachment and skin lesions. Some drugs, such as carbamazepine, have been reported to have a greater correlation to SJS. Although clozapine use has been mentioned as a risk factor for development of SJS, no report has clearly described the features of SJS as a reaction to clozapine use. Herein, we report the case of a patient presenting SJS after long-term clozapine treatment.Case report: Mr A was a 54-year-old male with a diagnosis of chronic schizophrenia. He was hospitalized in a mental institute and received clozapine 200 mg/day for 2 years, without discomfort or drug side effects. He developed acute-onset mouth edema, multiple oral and ocular ulcers, oral and ocular mucosa swelling, and multiple erythematous skin rashes over his entire body and extremities with hypertension and high fever. SJS was diagnosed after referral to a general hospital.Results: The SJS subsided under supportive treatment.Conclusion: Accumulated lymphocytes and macrophages in the epidermis and elevated TNF-α might cause an immune reaction and apoptosis and result in the clinical presentation of SJS. Clozapine is believed to modulate the immunologic reaction, and therefore might induce SJS through immunomodulation. This case highlights the importance of considering the possibility of SJS resulting from the use of drugs for which there are no reports of such a severe complication. Keywords: psychiatry, side effect, pharmacotherapy, adverse reaction, pharmacy

  16. Brief embryonic cadmium exposure induces a stress response and cell death in the developing olfactory system followed by long-term olfactory deficits in juvenile zebrafish

    International Nuclear Information System (INIS)

    The toxic effects of cadmium and other metals have been well established. A primary target of these metals is known to be the olfactory system, and fish exposed to a number of different waterborne metals display deficiencies in olfaction. Importantly, exposure over embryonic/larval development periods can cause deficits in chemosensory function in juvenile fish, but the specific cell types affected are unknown. We have previously characterized a transgenic zebrafish strain expressing the green fluorescent protein (eGFP) gene linked to the hsp70 gene promoter, and shown it to be a useful tool for examining cell-specific toxicity in living embryos and larvae. Here we show that the hsp70/eGFP transgene is strongly and specifically upregulated within the olfactory sensory neurons (OSNs) of transgenic zebrafish larvae following a brief 3-h exposure to water-borne cadmium. This molecular response was closely correlated to an endpoint for tissue damage within the olfactory placode, namely cell death. Furthermore, cadmium-induced olfactory cytotoxicity in zebrafish larvae gives rise to more permanent effects. Juvenile zebrafish briefly exposed to cadmium during early larval development display deficits in olfactory-dependent predator avoidance behaviors 4-6 weeks after a return to clean water. Lateral line neuromasts of exposed zebrafish larvae also activate both the endogenous hsp70 gene and the hsp70/eGFP transgene. The data reveal that even a very brief exposure period that gives rise to cell death within the developing olfactory placode results in long-term deficits in olfaction, and that hsp70/eGFP may serve as an effective indicator of sublethal cadmium exposure in sensory cells

  17. Sleep-deprivation induces changes in GABA(B and mGlu receptor expression and has consequences for synaptic long-term depression.

    Directory of Open Access Journals (Sweden)

    Ramakrishna Tadavarty

    Full Text Available Long term depression (LTD in the CA1 region of the hippocampus, induced with a 20-Hz, 30 s tetanus to Schaffer collaterals, is enhanced in sleep-deprived (SD rats. In the present study, we investigated the role of metabotropic glutamate receptors (mGluRs, γ-aminobutyric acid (GABA B receptors (GABA(B-Rs and N-methyl-D-aspartic acid receptors (NMDARs in the LTD of the population excitatory postsynaptic potential (pEPSP. The requirement of Ca(2+ from L- and T-type voltage-gated calcium channels (VGCCs and intracellular stores was also studied. Results indicate that mGluRs, a release of Ca(2+ from intracellular stores and GABA(B-Rs are required for LTD. Interestingly, while mGlu1Rs seem to be involved in both short-term depression and LTD, mGlu5Rs appear to participate mostly in LTD. CGP 55845, a GABA(B-R antagonist, partially suppressed LTD in normally sleeping (NS rats, while completely blocking LTD in SD rats. Moreover, GS-39783, a positive allosteric modulator for GABA(B-R, suppressed the pEPSP in SD, but not NS rats. Since both mGluRs and GABA(B-Rs seem to be involved in the LTD, especially in SD rats, we examined if the receptor expression pattern and/or dimerization changed, using immunohistochemical, co-localization and co-immunoprecipitation techniques. Sleep-deprivation induced an increase in the expression of GABA(B-R1 and mGlu1αR in the CA1 region of the hippocampus. In addition, co-localization and heterodimerization between mGlu1αR/GABA(B-R1 and mGlu1αR/GABA(B-R2 is enhanced in SD rats. Taken together, our findings present a novel form of LTD sensitive to the activation of mGluRs and GABA(B-Rs, and reveal, for the first time, that sleep-deprivation induces alterations in the expression and dimerization of these receptors.

  18. A new steroid-induced cataract model in the rat: long-term prednisolone applications with a minimum of X-irradiation.

    Science.gov (United States)

    Shui, Y B; Kojima, M; Sasaki, K

    1996-01-01

    In order to induce experimental steroid cataracts in rat eyes similar morphologically to those seen in human eyes, prednisolone acetate was administered either topically or systemically for 12 months with a low dose of X-irradiation as a cocataractogenic factor. Twenty-seven Brown-Norway rats were randomly divided into a control group (group I) with no steroid administration; an eyedrop group (group II) with a daily 1% prednisolone acetate instillation of a total volume of 1.0 mg/kg in both eyes, and a systemic group (group III) with a daily intramuscular injection of 0.8-1.0 mg/kg prednisolone acetate. The right eyes of animals in each group were X-irradiated with a single dose of 2 Gy. Topical and systemic steroid administrations started 2 weeks after X-irradiation. Anterior segment changes were documented with a slitlamp microscope and an anterior eye segment analysis system once a month. Body weight and blood glucose levels were examined every week and every 2 weeks, respectively. The mortality rates in groups I, II and III were 0, 11 (1/9) and 25% (3/12), respectively. The both lenses in group I showed a gradual increase in light-scattering intensity in the nuclear and supranuclear regions over time. Initial lens changes in both steroid-treated groups were Y-suture dissociation and a slight increase in light-scattering intensity in the posterior supranuclear region 3 months after prednisolone administration. Opacification of the anterior shallow cortex and the posterior subcapsular layer was observed after 10 months. X-irradiated eyes showed more prominent lens opacification as compared with nonirradiated eyes after 10 months in both group II and group III. Either topical or systemic administrations of prednisolone acetate over a long term successfully induced morphological lenticular changes in the rat similar to those found in human steroid-induced cataracts. A low dose of X-irradiation effectively accelerated opacification as a cocataractogenic risk. This

  19. Peripubertal aromatase inhibition in male rats has adverse long-term effects on bone strength and growth and induces prostatic hyperplasia.

    Science.gov (United States)

    Bajpai, Anurag; Simm, Peter J; McPherson, Stephen J; Russo, Vincenzo C; Azar, Walid J; Wark, John D; Risbridger, Gail P; Werther, George A

    2010-10-01

    Aromatase inhibitors have been increasingly used in boys with growth retardation to prolong the duration of growth and increase final height. Multiple important roles of oestrogen in males point to potential adverse effects of this strategy. Although the deleterious effects of aromatase deficiency in early childhood and adulthood are well documented, there is limited information about the potential long-term adverse effects of peripubertal aromatase inhibition. To address this issue, we evaluated short-term and long-term effects of peripubertal aromatase inhibition in an animal model. Peripubertal male Wistar rats were treated with aromatase inhibitor letrozole or placebo and followed until adulthood. Letrozole treatment caused sustained reduction in bone strength and alteration in skeletal geometry, lowering of IGF1 levels, inhibition of growth resulting in significantly lower weight and length of treated animals and development of focal prostatic hyperplasia. Our observation of adverse long-term effects after peripubertal male rats were exposed to aromatase inhibitors highlights the need for further characterisation of long-term adverse effects of aromatase inhibitors in peripubertal boys before further widespread use is accepted. Furthermore, this suggests the need to develop more selective oestrogen inhibition strategies in order to inhibit oestrogen action on the growth plate, while beneficial effects in other tissues are preserved. PMID:20675302

  20. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis.

    Science.gov (United States)

    Dubin, Krista; Callahan, Margaret K; Ren, Boyu; Khanin, Raya; Viale, Agnes; Ling, Lilan; No, Daniel; Gobourne, Asia; Littmann, Eric; Huttenhower, Curtis; Pamer, Eric G; Wolchok, Jedd D

    2016-01-01

    The composition of the intestinal microbiota influences the development of inflammatory disorders. However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota's composition. Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune-mediated colitis. Here we conduct a prospective study of patients with metastatic melanoma undergoing ipilimumab treatment and correlate the pre-inflammation faecal microbiota and microbiome composition with subsequent colitis development. We demonstrate that increased representation of bacteria belonging to the Bacteroidetes phylum is correlated with resistance to the development of checkpoint-blockade-induced colitis. Furthermore, a paucity of genetic pathways involved in polyamine transport and B vitamin biosynthesis is associated with an increased risk of colitis. Identification of these biomarkers may enable interventions to reduce the risk of inflammatory complications following cancer immunotherapy. PMID:26837003

  1. Astigmatismo induzido na cirurgia extracapsular da catarata: acompanhamento a longo prazo Induced astigmatism in extracapsular cataract extraction: long-term follow-up

    Directory of Open Access Journals (Sweden)

    Almir Ghiaroni

    2004-02-01

    Full Text Available OBJETIVO: Estudar o comportamento do astigmatismo induzido a longo prazo em uma série de pacientes submetidos à cirurgia extracapsular da catarata, nos quais foi utilizada incisão límbica posterior superior suturada com pontos separados de mononylon 10-0. MÉTODOS: Foram estudados 38 olhos, de 35 pacientes, sendo 21 do sexo feminino e 14 do sexo masculino, com idades variando entre 47 e 85 anos (média = 70,17 anos. Todos os casos foram operados pelo mesmo cirurgião. O período de acompanhamento pós-operatório variou de 15 a 33 meses (média = 22,07 meses. Nenhum dos casos teve qualquer dos pontos seccionado ou removido. Todos os pacientes atingiram acuidade visual corrigida igual ou superior a 0,5. Para o cálculo do astigmatismo induzido foram consideradas as medidas ceratométricas pré e pós-operatórias e foi utilizado um programa desenvolvido por Jaffe. RESULTADOS: O astigmatismo induzido variou de 0,13 dioptria (D a 2,74 D (média = 1,19 D. Em relação aos eixos, na maioria dos casos houve indução de astigmatismo a favor da regra (60,52%. Foi observada mudança significativa no valor dióptrico do astigmatismo quando foram comparadas as leituras ceratométricas registradas pré-operatoriamente até a segunda semana pós-operatória, entre o primeiro e o terceiro meses pós-operatórios, entre o terceiro e o sexto meses pós-operatórios e após o décimo-segundo mês pós-operatório. CONCLUSÃO: Quando o mononylon 10-0 é utilizado como material de sutura na cirurgia extracapsular da catarata, os valores de astigmatismo a favor da regra inicialmente observados tendem a diminuir com o tempo.PURPOSE: To study the long-term behavior of induced astigmatism in a series of patients who underwent extracapsular extraction in which a superoposterior limbal incision sutured with interrupted 10-0 mononylon sutures was performed. METHODS: 38 eyes of 35 patients were studied, 21 females and 17 males, with ages varying from 47 to 85 year

  2. Study design: two long-term observational studies of the biosimilar filgrastim Nivestim™ (Hospira filgrastim) in the treatment and prevention of chemotherapy-induced neutropenia

    International Nuclear Information System (INIS)

    407 patients, and NEXT in September 2013 with 2123 patients. Last patient, last visit for each study will be December 2013 and March 2014 respectively. The NEXT and VENICE studies will provide long-term safety, efficacy and practice pattern data in patients receiving Nivestim™ to support myelosuppressive chemotherapy in real world clinical practice. These data will improve our understanding of the performance of Nivestim™ in patients encountered in the general patient population. NEXT http://www.clinicaltrials.gov/ct2/show/NCT01574235?term, VENICE http://www.clinicaltrials.gov/ct2/show/NCT01627990?term

  3. Long-term aerobic swimming training by rats reduces the number of aberrant crypt foci in 1,2-dimethylhydrazine-induced colon cancer

    Directory of Open Access Journals (Sweden)

    W. Lunz

    2008-11-01

    Full Text Available We determined the effect of long-term aerobic swimming training regimens of different intensities on colonic carcinogenesis in rats. Male Wistar rats (11 weeks old were given 4 subcutaneous injections (40 mg/kg body weight each of 1,2-dimethyl-hydrazine (DMH, dissolved in 0.9% NaCl containing 1.5% EDTA, pH 6.5, at 3-day intervals and divided into three exercise groups that swam with 0% body weight (EG1, N = 11, 2% body weight (EG2, N = 11, and 4% body weight of load (EG3, N = 10, 20 min/day, 5 days/week for 35 weeks, and one sedentary control group (CG, N = 10. At sacrifice, the colon was removed and counted for tumors and aberrant crypt foci. Tumor size was measured and intra-abdominal fat was weighed. The mean number of aberrant crypt foci was reduced only for EG2 compared to CG (26.21 ± 2.99 vs 36.40 ± 1.53 crypts; P < 0.05. Tumor incidence was not significantly different among groups (CG: 90%; EG1: 72.7%; EG2: 90%; EG3: 80%. Swimming training did not affect either tumor multiplicity (CG: 2.30 ± 0.58; EG1: 2.09 ± 0.44; EG2: 1.27 ± 0.19; EG3: 1.50 ± 0.48 tumors or size (CG: 1.78 ± 0.24; EG1: 1.81 ± 0.14; EG2: 1.55 ± 0.21; EG3: 2.17 ± 0.22 cm³. Intra-abdominal fat was not significantly different among groups (CG: 10.54 ± 2.73; EG1: 6.12 ± 1.15; EG2: 7.85 ± 1.24; EG3: 5.11 ± 0.74 g. Aerobic swimming training with 2% body weight of load protected against the DMH-induced preneoplastic colon lesions, but not against tumor development in the rat.

  4. Effect of long-term compost and inorganic fertilizer application on background N2O and fertilizer-induced N2O emissions from an intensively cultivated soil.

    Science.gov (United States)

    Ding, Weixin; Luo, Jiafa; Li, Jie; Yu, Hongyan; Fan, Jianling; Liu, Deyan

    2013-11-01

    The influence of inorganic fertilizer and compost on background nitrous oxide (N2O) and fertilizer-induced N2O emissions were examined over a maize-wheat rotation year from June 2008 to May 2009 in a fluvo-aquic soil in Henan Province of China where a field experiment had been established in 1989 to evaluate the long-term effects of manure and fertilizer on soil organic status. The study involved five treatments: compost (OM), fertilizer NPK (nitrogen-phosphorus-potassium, NPK), half compost N plus half fertilizer N (HOM), fertilizer NK (NK), and control without any fertilizer (CK). The natural logarithms of the background N2O fluxes were significantly (P<0.05) correlated with soil temperature, but not with soil moisture, during the maize or wheat growing season. The 18-year application of compost alone and inorganic fertilizer not only significantly (P<0.05) increased soil organic carbon (SOC) by 152% and 10-43% (respectively), but also increased background N2O emissions by 106% and 48-76% (respectively) compared with the control. Total N in soils was a better indicator for predicting annual background N2O emission than SOC. The estimated emission factor (EF) of mineralized N, calculated by dividing annual N2O emission by mineralized N was 0.13-0.19%, significantly (P<0.05) lower than the EF of added N (0.30-0.39%). The annual N2O emission in the NPK, HOM and OM soils amended with 300 kg ha(-1) organic or inorganic N was 1427, 1325 and 1178 g N ha(-1), respectively. There was a significant (P<0.05) difference between the NPK and OM. The results of this study indicate that soil indigenous N was less efficiently converted into N2O compared with exogenous N. Increasing SOC by compost application, then partially increasing N supply to crops instead of adding inorganic N fertilizer, may be an effective measure to mitigate N2O emissions from arable soils in the North China plain. PMID:23229048

  5. Long term e-archiving

    OpenAIRE

    Dobratz, Susanne

    2002-01-01

    Conclusions of the breakout session "Long term e-archiving". Looking at the motto of this workshop “Gaining independence with e-Print archives and OAI” it suggests first of all that using e-Print publishing methods especially in the sense of a scholarly non-profit publishing independently from any commercial publishing house offers a unique chance to scientists.

  6. Chimeric Allografts Induced by Short-Term Treatment With Stem Cell Mobilizing Agents Result in Long-Term Kidney Transplant Survival Without Immunosuppression: II, Study in Miniature Swine.

    Science.gov (United States)

    Cameron, A M; Wesson, R N; Ahmadi, A R; Singer, A L; Hu, X; Okabayashi, T; Wang, Y; Shigoka, M; Fu, Y; Gao, W; Raccusen, L C; Montgomery, R A; Williams, G M; Sun, Z

    2016-07-01

    Transplantation is now lifesaving therapy for patients with end-stage organ failure but requires lifelong immunosuppression with resultant morbidity. Current immunosuppressive strategies inhibit T cell activation and prevent donor-recipient engagement. Therefore, it is not surprising that few host cells are demonstrated in donor grafts. However, our recent small animal studies found large numbers of recipient stem cells present after transplantation and pharmacological mobilization, resulting in a chimeric, repopulated organ. We now confirm these findings in a well-characterized large animal preclinical model. Here, we show that AMD3100 and FK506 mobilization of endogenous stem cells immediately post kidney transplantation combined with repeat therapy at 1, 2, and 3 months led to drug-free long-term survival in maximally immunologically mismatched swine. Three long-term recipients have stable chimeric transplants, preserved antidonor skin graft responses, and normal serum creatinine levels despite withdrawal of all medication for 3 years. PMID:26748958

  7. Long-term inducible expression in striatal neurons from helper virus-free HSV-1 vectors that contain the tetracycline-inducible promoter system

    OpenAIRE

    Gao, Qingshen; Sun, Mei; Wang, Xiaodan; Zhang, Guo-rong; Geller, Alfred I.

    2006-01-01

    Direct gene transfer into neurons in the brain via a virus vector system has potential for both examining neuronal physiology and for developing gene therapy treatments for neurological diseases. Many of these applications require precise control of the levels of recombinant gene expression. The preferred method for controlling the levels of expression is by use of an inducible promoter system, and the tetracycline (tet)-inducible promoter system is the preferred system. Helper virus-free Her...

  8. Class IC antiarrhythmic drug induced atrial flutter: electrocardiographic and electrophysiological findings and their importance for long term outcome after right atrial isthmus ablation

    OpenAIRE

    Nabar, A; Rodriguez, L.; Timmermans, C; van Mechelen, R; Wellens, H

    2001-01-01

    OBJECTIVE—To describe the electrocardiographic and electrophysiological findings of new atrial flutter developing in patients taking class IC antiarrhythmic drugs for recurrent atrial fibrillation, and to report the long term results of right atrial isthmus ablation in relation to the ECG pattern of spontaneous atrial flutter.
DESIGN—Retrospective analysis.
SETTING—Tertiary care academic hospital.
PATIENTS—24 consecutive patients with atrial fibrillation (age 54 (12) years; 5 female, 19 male)...

  9. Survival or revival: long-term preservation induces a reversible viable but non-culturable state in methane-oxidizing bacteria

    OpenAIRE

    Hoefman, Sven; Van Hoorde, Koenraad; Boon, Nico; Vandamme, Peter; de Vos, Paul; Heylen, Kim

    2012-01-01

    Knowledge on long-term preservation of micro-organisms is limited and research in the field is scarce despite its importance for microbial biodiversity and biotechnological innovation. Preservation of fastidious organisms such as methane-oxidizing bacteria (MOB) has proven difficult. Most MOB do not survive lyophilization and only some can be cryopreserved successfully for short periods. A large-scale study was designed for a diverse set of MOB applying fifteen cryopreservation or lyophilizat...

  10. Protein Kinase M[Zeta] Is Essential for the Induction and Maintenance of Dopamine-Induced Long-Term Potentiation in Apical CA1 Dendrites

    Science.gov (United States)

    Navakkode, Sheeja; Sajikumar, Sreedharan; Sacktor, Todd Charlton; Frey, Julietta U.

    2010-01-01

    Dopaminergic D1/D5-receptor-mediated processes are important for certain forms of memory as well as for a cellular model of memory, hippocampal long-term potentiation (LTP) in the CA1 region of the hippocampus. D1/D5-receptor function is required for the induction of the protein synthesis-dependent maintenance of CA1-LTP (L-LTP) through activation…

  11. NOX1-induced accumulation of reactive oxygen species in abdominal fat-derived mesenchymal stromal cells impinges on long-term proliferation

    OpenAIRE

    Sela, M; Tirza, G; Ravid, O; Volovitz, I; Solodeev, I; Friedman, O; Zipori, D; E. Gur; Krelin, Y; Shani, N

    2015-01-01

    Mesenchymal stromal cells (MSCs) are multipotent and can be derived from different adult tissues including fat. Our repeated attempts to produce long-term proliferative cultures of rat abdominal adipose stem cells (aASCs) under normal oxygen concentration (21%) were unsuccessful. We set to examine the events controlling this cytostasis of aASCs and found that it resulted from overproduction of reactive oxygen species (ROS) that led to apoptosis. ROS overproduction in aASCs was accompanied by ...

  12. Repetitive long-term hyperbaric oxygen treatment (HBOT administered after experimental traumatic brain injury in rats induces significant remyelination and a recovery of sensorimotor function.

    Directory of Open Access Journals (Sweden)

    Klaus Kraitsy

    Full Text Available Cells in the central nervous system rely almost exclusively on aerobic metabolism. Oxygen deprivation, such as injury-associated ischemia, results in detrimental apoptotic and necrotic cell loss. There is evidence that repetitive hyperbaric oxygen therapy (HBOT improves outcomes in traumatic brain-injured patients. However, there are no experimental studies investigating the mechanism of repetitive long-term HBOT treatment-associated protective effects. We have therefore analysed the effect of long-term repetitive HBOT treatment on brain trauma-associated cerebral modulations using the lateral fluid percussion model for rats. Trauma-associated neurological impairment regressed significantly in the group of HBO-treated animals within three weeks post trauma. Evaluation of somatosensory-evoked potentials indicated a possible remyelination of neurons in the injured hemisphere following HBOT. This presumption was confirmed by a pronounced increase in myelin basic protein isoforms, PLP expression as well as an increase in myelin following three weeks of repetitive HBO treatment. Our results indicate that protective long-term HBOT effects following brain injury is mediated by a pronounced remyelination in the ipsilateral injured cortex as substantiated by the associated recovery of sensorimotor function.

  13. Repetitive Long-Term Hyperbaric Oxygen Treatment (HBOT) Administered after Experimental Traumatic Brain Injury in Rats Induces Significant Remyelination and a Recovery of Sensorimotor Function

    Science.gov (United States)

    Grossauer, Stefan; Bruckmann, Lukas; Pfleger, Florentina; Ropele, Stefan; Fazekas, Franz; Gruenbacher, Gerda; Patz, Silke; Absenger, Markus; Porubsky, Christian; Smolle-Juettner, Freyja; Tezer, Irem; Molcanyi, Marek; Fasching, Ulrike; Schaefer, Ute

    2014-01-01

    Cells in the central nervous system rely almost exclusively on aerobic metabolism. Oxygen deprivation, such as injury-associated ischemia, results in detrimental apoptotic and necrotic cell loss. There is evidence that repetitive hyperbaric oxygen therapy (HBOT) improves outcomes in traumatic brain-injured patients. However, there are no experimental studies investigating the mechanism of repetitive long-term HBOT treatment-associated protective effects. We have therefore analysed the effect of long-term repetitive HBOT treatment on brain trauma-associated cerebral modulations using the lateral fluid percussion model for rats. Trauma-associated neurological impairment regressed significantly in the group of HBO-treated animals within three weeks post trauma. Evaluation of somatosensory-evoked potentials indicated a possible remyelination of neurons in the injured hemisphere following HBOT. This presumption was confirmed by a pronounced increase in myelin basic protein isoforms, PLP expression as well as an increase in myelin following three weeks of repetitive HBO treatment. Our results indicate that protective long-term HBOT effects following brain injury is mediated by a pronounced remyelination in the ipsilateral injured cortex as substantiated by the associated recovery of sensorimotor function. PMID:24848795

  14. Alterations in task-induced activity and resting-state fluctuations in visual and DMN areas revealed in long-term meditators.

    Science.gov (United States)

    Berkovich-Ohana, Aviva; Harel, Michal; Hahamy, Avital; Arieli, Amos; Malach, Rafael

    2016-07-15

    Recently we proposed that the information contained in spontaneously emerging (resting-state) fluctuations may reflect individually unique neuro-cognitive traits. One prediction of this conjecture, termed the "spontaneous trait reactivation" (STR) hypothesis, is that resting-state activity patterns could be diagnostic of unique personalities, talents and life-styles of individuals. Long-term meditators could provide a unique experimental group to test this hypothesis. Using fMRI we found that, during resting-state, the amplitude of spontaneous fluctuations in long-term mindfulness meditation (MM) practitioners was enhanced in the visual cortex and significantly reduced in the DMN compared to naïve controls. Importantly, during a visual recognition memory task, the MM group showed heightened visual cortex responsivity, concomitant with weaker negative responses in Default Mode Network (DMN) areas. This effect was also reflected in the behavioral performance, where MM practitioners performed significantly faster than the control group. Thus, our results uncover opposite changes in the visual and default mode systems in long-term meditators which are revealed during both rest and task. The results support the STR hypothesis and extend it to the domain of local changes in the magnitude of the spontaneous fluctuations. PMID:27109713

  15. A cost of long-term memory in Drosophila

    OpenAIRE

    Mery, Frederic; Kawecki, Tadeusz J

    2005-01-01

    Two distinct forms of consolidated associative memory are known in Drosophila: long-term memory and so-called anesthesia-resistant memory. Long-term memory is more stable, but unlike anesthesia-resistant memory, its formation requires protein synthesis. We show that flies induced to form long-term memory become more susceptible to extreme stress (such as desiccation). In contrast, induction of anesthesia-resistant memory had no detectable effect on desiccation resistance. This finding may hel...

  16. Long-term care financing through Federal tax incentives

    OpenAIRE

    Donald W. Moran; Weingart, Janet M.

    1988-01-01

    Congress and the Administration are currently exploring various methods of promoting access to long-term care. In this article, an inventory of recent legislative proposals for using the Federal tax code to expand access to long-term care services is provided. Proposals are arrayed along a functional typology that includes tax mechanisms to encourage accumulation of funds, promote purchase of long-term care insurance, or induce the diversion of funds accumulated for another purpose (such as i...

  17. Inducible scAAV2.GRE.MMP1 lowers IOP long-term in a large animal model for steroid-induced glaucoma gene therapy.

    Science.gov (United States)

    Borrás, T; Buie, L K; Spiga, M G

    2016-05-01

    Current treatment of glaucoma relies on administration of daily drops or eye surgery. A gene therapy approach to treat steroid-induced glaucoma would bring a resolution to millions of people worldwide who depend on glucocorticoid therapy for a myriad of inflammatory disorders. Previously, we had characterized a short-term Adh.GRE.MMP1 gene vector for the production of steroid-induced MMP1 in the trabecular meshwork and tested reduction of elevated intraocular pressure (IOP) in a sheep model. Here we conducted a trial transferring the same transgene cassette to a clinically safe vector (scAAV2), and extended the therapeutic outcome to longer periods of times. No evidence of ocular and/or systemic toxicity was observed. Viral genome distributions showed potential reinducible vector DNAs in the trabecular meshwork (0.4 v.g. per cell) and negligible copies in six major internal organs (0.00002-0.005 v.g. per cell). Histological sections confirmed successful transduction of scAAV2.GFP to the trabecular meshwork. Optimization of the sheep steroid-induced hypertensive model revealed that topical ophthalmic drug difluprednate 0.05% (durezol) induced the highest IOP elevation in the shortest time. This is the first efficacy/toxicity study of a feasible gene therapy treatment of steroid-induced hypertension using clinically accepted self-complementary adeno-associated vectors (scAAV) vectors in a large animal model. PMID:26855269

  18. Nuclear Energy, Long Term Requirements

    International Nuclear Information System (INIS)

    There are serious warnings about depletion of oil and gas and even more serious warnings about dangers of climate change caused by emission of carbon dioxide. Should developed countries be called to replace CO2 emitting energy sources as soon as possible, and the time available may not be longer then few decades, can nuclear energy answer the call and what are the requirements? Assuming optimistic contribution of renewable energy sources, can nuclear energy expand to several times present level in order to replace large part of fossil fuels use? Paper considers intermediate and long-term requirements. Future of nuclear power depends on satisfactory answers on several questions. First group of questions are those important for near and intermediate future. They deal with economics and safety of nuclear power stations in the first place. On the same time scale a generally accepted concept for radioactive waste disposal is also required. All these issues are in the focus of present research and development. Safer and more economical reactors are targets of international efforts in Generation IV and INPRO projects, but aiming further ahead these innovative projects are also addressing issues such as waste reduction and proliferation resistance. However, even assuming successful technical development of these projects, and there is no reason to doubt it, long term and large-scale nuclear power use is thereby not yet secured. If nuclear power is to play an essential role in the long-term future energy production and in reduction of CO2 emission, than several additional questions must be replied. These questions will deal with long-term nuclear fuel sufficiency, with necessary contribution of nuclear power in sectors of transport and industrial processes and with nuclear proliferation safety. This last issue is more political then technical, thus sometimes neglected by nuclear engineers, yet it will have essential role for the long-term prospects of nuclear power. The

  19. Effect of alpha and beta adrenergic blockade on epinephrine induced pulmonary insufficiency.

    Science.gov (United States)

    Berk, J L; Hagen, J F; Koo, R

    1976-04-01

    Recent studies demonstrated that epinephrine causes significant pulmonary A-V shunting. This study reports the effect of alpha and beta adrenergic blockade on this shunting. Sixty-three anesthetized mongrel dogs were ventilated with a mechanical respirator. Measurements of (1) the pulmonary shunt, (2) cardiac output, (3) mean pulmonary artery, pulmonary capillary wedge and systemic pressures, and (4) pulmonary and systemic vascular resistances were obtained at 5, 15 and 30 minute intervals during the first hour and hourly for 5 hours. Fifteen dogs received no treatment. All others received epinephrine hydrochloride, 2 mug/kg/min for 5 hours. Ten received epinephrine only. Ten were pretreated with propranolol hydrochloride, 250 mug/kg, 12 with phenoxybenzamine, 1 mg/kg, and 16 with phenoxybenzamine and propranolol. Propranolol significantly decreased the epinephrine induced pulmonary shunt at all times and was the most effective drug. Phenoxybenzamine decreased the early shunting, but less than propranolol, and did not decrease the late shunting. Blockade with propranolol and phenoxybenzamine was less effective than propranolol alone. Based on the observed hemodynamic changes it was suggested that beta blockade is effective in reducing epinephrine induced pulmonary insufficiency by favorably altering the flow and distribution of pulmonary blood flow which in turn decreases epinephrine induced ventilation-perfusion inequalities and capillary hypertension both of which result in shunting. Conversely phenoxybenzamine has an unfavorable effect on the pulmonary flow. These studies support previous work in animals and man which showed that beta adrenergic stimulation is important in the pathogenesis of pulmonary insufficiency. Because the amounts of epinephrine used produce blood levels observed in critical illness, these studies add support to a relationship between the increased catecholamine stimulation of critical illness and the associated and often unexplained

  20. Quantum Communication and Computing With Atomic Ensembles Using Light-Shift Imbalance Induced Blockade

    OpenAIRE

    Shahriar, M. S.; Pati, G. S.; Salit, K.

    2006-01-01

    Recently, we have shown that for conditions under which the so-called light-shift imbalance induced blockade (LSIIB) occurs, the collective excitation of an ensemble of a multi-level atom can be treated as a closed two level system. In this paper, we describe how such a system can be used as a quantum bit (qubit) for quantum communication and quantum computing. Specifically, we show how to realize a C-NOT gate using the collective qubit and an easily accessible ring cavity, via an extension o...

  1. Comparing long term energy scenarios

    International Nuclear Information System (INIS)

    Major projection studies by international organizations and senior analysts have been compared with reference to individual key parameters (population, energy demand/supply, resources, technology, emissions and global warming) to understand trends and implications of the different scenarios. Then, looking at the long term (i.e., 2050 and beyond), parameters and trends have been compared together to understand and quantify whether and when possible crisis or market turbulence might occur due to shortage of resources or environmental problems

  2. CD44+/CD105+ Human Amniotic Fluid Mesenchymal Stem Cells Survive and Proliferate in the Ovary Long-Term in a Mouse Model of Chemotherapy-Induced Premature Ovarian Failure

    OpenAIRE

    LIU, TE; HUANG, YONGYI; Guo, Lihe; Cheng, Weiwei; Zou, Gang

    2012-01-01

    Objectives: Stem cell transplantation has been reported to rescue ovarian function in a preclinical mouse model of chemotherapy-induced premature ovarian failure (POF); however, maintaining the survival and self-renewal of transplanted seed cells in ovarian tissues over the long-term remains a troublesome issue. In this study we aimed to determine whether the CD44+/CD105+ human amniotic fluid cell (HuAFCs) subpopulation represent potential seed cells for stem cell transplantation treatments i...

  3. Light-Shift Imbalance Induced Blockade of Collective Excitations Beyond the Lowest Order

    CERN Document Server

    Shahriar, M S; Pati, G S; Gopal, V; Salit, K

    2006-01-01

    Current proposals focusing on neutral atoms for quantum computing are mostly based on using single atoms as quantum bits (qubits), while using cavity induced coupling or dipole-dipole interaction for two-qubit operations. An alternative approach is to use atomic ensembles as qubits. However, when an atomic ensemble is excited, by a laser beam matched to a two-level transition (or a Raman transition) for example, it leads to a cascade of many states as more and more photons are absorbed^1. In order to make use of an ensemble as a qubit, it is necessary to disrupt this cascade, and restrict the excitation to the absorption (and emission) of a single photon only. Here, we show how this can be achieved by using a new type of blockade mechanism, based on the light-shift imbalance (LSI) in a Raman transition. We describe first a simple example illustrating the concept of light shift imbalanced induced blockade (LSIIB) using a multi-level structure in a single atom, and show verifications of the analytic prediction ...

  4. The effects of calcium channel blockade on agouti-induced obesity

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Han; Moustaid, N.; Zemel, M.B. [Univ. of Tennessee, Knoxville, TN (United States)] [and others

    1996-12-01

    We have previously observed that obese viable yellow (A{sup vy}/a) mice exhibit increased intracellular Ca{sup 2+} ([Ca{sup 2+}]i) and fatty acid synthase (FAS) gene expression; further, recombinant agouti protein increases in cultured adipocytes and these effects are inhibited by Ca{sup 2+} channel blockade. Accordingly, we determined the effect of Ca{sup 2+} channel blockade (nifedipine for 4 wk) on FAS and obesity in transgenic mice expressing the agouti gene in a ubiquitous manner. The transgenic mice initially were significantly heavier (30.5 {+-} 0.6 vs. 27.3 {+-} 0.3 g; P<0.001) and exhibited a 0.81{degrees}C lower initial core temperature (P<0.0005), an approximately twofold increase in fat pad weights (P=0.002), a sevenfold increase in adipose FAS activity (P=0.009), and a twofold increase in plasma insulin level (P<0.05) compared to control mice. Nifedipine treatment resulted in an 18% decrease in fat pad weights (P<0.007) and a 74% decrease in adipose FAS activity (P=0.03), normalized circulating insulin levels and insulin sensitivity (P,0.05), and transiently elevated core temperature in the transgenic mice, but was without effect in the control mice. These data suggest that agouti regulates FAS, fat storage, and possibly thermogenesis, at least partially, via a [Ca{sup 2+}]{sub i}-dependent mechanism, and that Ca{sup 2+} channel blockade may partially attenuate agouti-induced obesity. 42 refs., 4 figs., 1 tab.

  5. Recovery from mivacurium-induced neuromuscular blockade is not affected by anticonvulsant therapy.

    Science.gov (United States)

    Jellish, W S; Thalji, Z; Brundidge, P K; Tempelhoff, R

    1996-01-01

    Long-term chronic anticonvulsant therapy produces a resistance to the effects of all nondepolarizing neuromuscular blocking agents studied to date. Since the metabolism of mivacurium is unique among the nondepolarizing neuromuscular blocking agents, the effect of anticonvulsants on its recovery parameters was examined. Forty-five patients were separated into three groups based on the number of chronic anticonvulsant medications the subjects were taking: subjects in group 1, the control group, took no anticonvulsant medication; group 2 subjects took one medication; and group 3 subjects took two medications. Mivacurium, 0.15 mg/kg i.v., was administered after induction of general anesthesia with thiopental sodium, 4-6 mg/kg, and fentanyl 2-4 micrograms/kg i.v. Maintenance anesthesia consisted of N2O in O2. 0.2-0.3% end-tidal isoflurane, and a fentanyl infusion. The evoked compound electromyograph (ECEMG) of the adductor pollicis-brevis muscle was measured for time of onset, T-1 (time at which ECEMG signal reaches 5, 25, 50, and 75% of baseline), TR (TOF ratio), and recovery index. T-1 at 25% was 18.2 +/- 1.8, 20.7 +/- 1.9, and 21.5 +/- 1.4 min for groups 1, 2, and 3, respectively, with TR at 25% being 23.7 +/- 2.3, 26.9 +/- 2.4, and 27.3 +/- 2.3 min. No significant differences were noted in neuromuscular recovery between groups at any time point. These results fail to demonstrate the resistance to the nondepolarizing neuromuscular blockade of mivacurium that has been observed with other nondepolarizing agents. PMID:8719185

  6. Long term stability of power systems

    Energy Technology Data Exchange (ETDEWEB)

    Kundur, P.; Gao, B. [Powertech Labs. Inc., Surrey, BC (Canada)

    1994-12-31

    Power system long term stability is still a developing subject. In this paper we provide our perspectives and experiences related to long term stability. The paper begins with the description of the nature of the long term stability problem, followed by the discussion of issues related to the modeling and solution techniques of tools for long term stability analysis. Cases studies are presented to illustrate the voltage stability aspect and plant dynamics aspect of long term stability. (author) 20 refs., 11 figs.

  7. Long-term potentiation and long-term depression: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Timothy V.P. Bliss

    2011-01-01

    Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

  8. The effects of renin-angiotensin system blockade on the liver steatosis in rats on long-term high-fat diet%阻断肾素-血管紧张素系统对长期高脂喂养大鼠肝脂肪变性的影响

    Institute of Scientific and Technical Information of China (English)

    陈樱花; 袁莉; 陈媛媛; 齐翠娟

    2008-01-01

    Objective To observe the relationship between liver steatosis in rats with long-term high-caloric and high-fat diet and the expression of angiotensinogen(AGT)、uncoupling protein 2(UCP-2)and transforming growth factorβ1(TGFβ1).Then angiotensin-converting enzyme inhibitor(ACEI)and angiotensin Ⅱ receptor blocker(ARB)drugs were given to investigate whether rennin-angiotensin system (RAS)blockade can mitigate the liver steatosis and to probe its mechanisms.Methotis Forty male Wistar rats were divided into normal control group(NC group,n=10),high-calorie and high-fat fed group(HF group,n=10),ARB treated group(AR group,n=10)and ACEI treated group(AE group,n=10).Rats were fed with high-calorie and high-fat diet and given RAS inhibitor drugs(valsartan 40mg/kg to the AR group and perindopril 4 mg/kg to the AE group)for eight weeks.Serum TG,free fatty acids(FFAs) lever and the fat content in liver were then measured with biochemical tests;insulin resistance was evaluated with euglycemic hyperinsulinemia clamp technique,the expression of UCP-2 and TGFβI in liver tissue were examind with immunohistochemical staining and AGT mRNA,UCP-2 mRNA and TGFβ1 mRNA were tested with RT-PCR.Results With the administration of RAS inhibitor drugs,following changes were observed.The levels of TG and FFAs and the fat content in liver decreased(P<0.01 or P<0.05),insulin resistance in high-fat fed rats was improved(P<0.05),liver steatosis,inflammation and fibrosis were mitigated.The levels of UCP-2 decreased by 36.5%(P<0.05)in AE group and 42.5%(P<0.05)in AR group and TGFβ1 decreased by 37%(P<0.05)in AE group and 41.6%(P<0.05)in AR group as compared with the HF group with immunohistochemical staining.The expression of AGTmRNA decreased by 14.9%(P<0.05)in AE group and 21%(P<0.05)in AR group,UCP-2 mRNA decreased by 9%(P<0.05)in AE group and 11%(P<0.05)in AR group and TGFβ1 mRNA decreased by 17%(P<0.05)in AE group and 19%(P<0.05)in AR group as compared with the HF

  9. Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

    Science.gov (United States)

    Rouger, Karl; Larcher, Thibaut; Dubreil, Laurence; Deschamps, Jack-Yves; Le Guiner, Caroline; Jouvion, Gregory; Delorme, Bruno; Lieubeau, Blandine; Carlus, Marine; Fornasari, Benoît; Theret, Marine; Orlando, Priscilla; Ledevin, Mireille; Zuber, Céline; Leroux, Isabelle; Deleau, Stéphane; Guigand, Lydie; Testault, Isabelle; Le Rumeur, Elisabeth; Fiszman, Marc; Chérel, Yan

    2011-01-01

    Duchenne muscular dystrophy (DMD) is a genetic progressive muscle disease resulting from the lack of dystrophin and without effective treatment. Adult stem cell populations have given new impetus to cell-based therapy of neuromuscular diseases. One of them, muscle-derived stem cells, isolated based on delayed adhesion properties, contributes to injured muscle repair. However, these data were collected in dystrophic mice that exhibit a relatively mild tissue phenotype and clinical features of DMD patients. Here, we characterized canine delayed adherent stem cells and investigated the efficacy of their systemic delivery in the clinically relevant DMD animal model to assess potential therapeutic application in humans. Delayed adherent stem cells, named MuStem cells (muscle stem cells), were isolated from healthy dog muscle using a preplating technique. In vitro, MuStem cells displayed a large expansion capacity, an ability to proliferate in suspension, and a multilineage differentiation potential. Phenotypically, they corresponded to early myogenic progenitors and uncommitted cells. When injected in immunosuppressed dystrophic dogs, they contributed to myofiber regeneration, satellite cell replenishment, and dystrophin expression. Importantly, their systemic delivery resulted in long-term dystrophin expression, muscle damage course limitation with an increased regeneration activity and an interstitial expansion restriction, and persisting stabilization of the dog's clinical status. These results demonstrate that MuStem cells could provide an attractive therapeutic avenue for DMD patients. PMID:21924229

  10. Long-term progestin contraceptives (LTPOC induce aberrant angiogenesis, oxidative stress and apoptosis in the guinea pig uterus: A model for abnormal uterine bleeding in humans

    Directory of Open Access Journals (Sweden)

    Buchwalder Lynn

    2010-04-01

    Full Text Available Abstract Background Irregular uterine bleeding is the major side effect of, and cause for, discontinuation of long-term progestin-only contraceptives (LTPOCs. The endometria of LTPOC-treated women display abnormally enlarged, fragile blood vessels (BV, decreased endometrial blood flow and oxidative stress. However, obtaining sufficient, good quality tissues have precluded elucidation of the mechanisms underlying these morphological and functional vascular changes. Methods The current study assessed the suitability of the guinea pig (GP as a model for evaluating the uterine effects of LTPOC administration. Thus GPs were treated with a transdermal pellet for 21 days and examined for endometrial histology, angiogenic markers as well as markers of oxidative stress and apoptosis. Results and Discussion We now demonstrate that GP uteri were enlarged by both estradiol (E2 and medroxyprogesterone acetate (MPA (p Conclusions LTPOC exposure alters endometrial vascular and tissue morphology consistent with oxidative stress and apoptosis in a complex interplay with endogenous estrogens. These findings are remarkably similar to in vivo change observed in the human uterus following LTPOC administration. Hence, the GP is an excellent model for the study of LTPOC effects on the uterus and will be extremely useful in determining the mechanistic pathways involved in this process which cannot be conducted on humans.

  11. Cortical auditory deafferentation induces long-term plasticity in the inferior colliculus of adult rats: Microarray and qPCR analysis.

    Directory of Open Access Journals (Sweden)

    Cheryl Clarkson

    2012-11-01

    Full Text Available The cortico-collicular pathway is a bilateral excitatory projection from the cortex to the inferior colliculus (IC. It is asymmetric and predominantly ipsilateral. Using microarrays and RT-qPCR we analyzed changes in gene expression in the IC after unilateral lesions of the auditory cortex, comparing the ICs ipsi- and contralateral to the lesioned side. At 15 days after surgery there were mainly changes in gene expression in the IC ipsilateral to the lesion. Regulation primarily involved inflammatory cascade genes, suggesting a direct effect of degeneration more than a neuronal plastic reorganization. Ninety days after the cortical lesion the ipsilateral IC showed a significant up-regulation of genes involved in apoptosis and axonal regeneration combined with a down-regulation of genes involved in neurotransmission, synaptic growth and gap junction assembly. In contrast, the contralateral IC at 90 days post-lesion showed an up-regulation in genes primarily related to neurotransmission, cell proliferation and synaptic growth. There was also a down-regulation in autophagy and neuroprotection genes. These findings suggest that the reorganization in the IC after descending pathway deafferentation is a long-term process involving extensive changes in gene expression-regulation. Regulated genes are involved in many different neuronal functions, and the number and gene rearrangement profile seems to depend on the density of loss of the auditory cortical inputs.

  12. Sugammadex 4.0 mg kg-1 reversal of deep rocuronium-induced neuromuscular blockade

    DEFF Research Database (Denmark)

    Yu, Buwei; Wang, Xiangrui; Hansen, Søren Helbo;

    2014-01-01

    Objective: Maintenance of deep Neuro Muscular Blockade (NMB) until the end of surgery may be beneficial in some surgical procedures. The selective relaxant binding agent sugammadex rapidly reverses deep levels of rocuronium-induced NMB. The purpose of this study was to evaluate the efficacy and s...

  13. Ghrelin and PYY levels in adolescents with severe obesity: effects of weight loss induced by long-term exercise training and modified food habits.

    Science.gov (United States)

    Gueugnon, Carine; Mougin, Fabienne; Nguyen, Nhu Uyen; Bouhaddi, Malika; Nicolet-Guénat, Marie; Dumoulin, Gilles

    2012-05-01

    This study investigated (a) changes in ghrelin and peptide YY (PYY) concentrations during a weight reduction programme and (b) baseline ghrelin and PYY levels as predictors of weight loss in 32 severely obese adolescents (BMI z score = 4.1). Subjects spent an academic year in an institution for childhood obesity. Fasting ghrelin and PYY, leptin, insulin levels and insulin resistance were measured at baseline (month 0) and during the programme (months 3, 6, 9). In addition, 15 normal-weight teenagers served as reference for the baseline assessments. At baseline, obese teenagers had lower ghrelin and PYY concentrations than normal-weight adolescents (P < 0.05). Moreover, they showed significantly higher leptin, insulin levels and homeostasis model assessment (HOMA) (P < 0.0001). During the lifestyle modification, there was a significant decrease in body weight among obese teenagers, associated with an increase in ghrelin (apparent from month 6; P < 0.05), a decrease in leptin (from month 3; P < 0.05) and a decrease in insulin and HOMA (from month 3; P < 0.0001), without any significant change in PYY. Anthropometrical changes were correlated neither with baseline ghrelin levels nor with changes in ghrelin and PYY after the lifestyle modification. However, higher baseline PYY tended to correlate with greater anthropometrical changes (P < 0.1). In adolescents with severe obesity, a long-term combination of supervised aerobic exercises and a balanced diet led to weight reduction and increased ghrelin concentrations, without any change in PYY concentrations. Moreover, baseline PYY concentrations might be considered as predictors of weight loss. PMID:21909986

  14. Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells

    International Nuclear Information System (INIS)

    The cumulative exposure to estrogens is an important determinant in the risk of breast cancer, yet the full range of mechanisms involving estrogens in the genesis and progression of breast cancer remains a subject of debate. Interactions of estrogens and environmental toxicants have received attention as putative factors contributing to carcinogenesis. Mechanistic studies have demonstrated interactions between estrogen receptor α (ERα) and the aryl hydrocarbon receptor (AhR), with consequences on the genes that they regulate. Many studies of ERα and AhR-mediated effects and crosstalk between them have focused on the initial molecular events. In this study, we investigated ERα- and AhR-mediated effects in long-term estrogen exposed (LTEE) MCF-7 human breast cancer cells, which were obtained by continuous culturing for at least 12 weeks in medium supplemented with 1 nM of 17β-estradiol (E2). With these LTEE cells and with parallel control cells cultured without E2 supplementation, we performed an extensive study of cytochrome P450 (CYP) induction, carcinogen bioactivation, global gene expression, and tumorigenicity in immunocompromised mice. We found that LTEE cells, in comparison with control cells, had higher levels of AhR mRNA and protein, greater responsiveness for AhR-regulated CYP1A1 and CYP1B1 induction, a 6-fold higher initial level of benzo(a)pyrene-DNA adducts as determined by liquid chromatography tandem mass spectrometry, marked differences in the expression of numerous genes, and a higher rate of E2-dependent tumor growth as xenografts. These studies indicate that LTEE causes adaptive responses in MCF-7 cells, which may reflect processes that contribute to the overall carcinogenic effect of E2.

  15. Milk from dams fed an obesogenic diet combined with a high-fat/high-sugar diet induces long-term abnormal mammary gland development in the rabbit.

    Science.gov (United States)

    Hue-Beauvais, C; Koch, E; Chavatte-Palmer, P; Galio, L; Chat, S; Letheule, M; Rousseau-Ralliard, D; Jaffrezic, F; Laloë, D; Aujean, E; Révillion, F; Lhotellier, V; Gertler, A; Devinoy, E; Charlier, M

    2015-04-01

    Alterations to the metabolic endocrine environment during early life are crucial to mammary gland development. Among these environmental parameters, the initial nutritional event after birth is the consumption of milk, which represents the first maternal support provided to mammalian newborns. Milk is a complex fluid that exerts effects far beyond its immediate nutritional value. The present study, therefore, aimed to determine the effect of the nutritional changes during the neonatal and prepubertal periods on the adult mammary phenotype. Newborn rabbits were suckled by dams fed a high-fat/high-sugar obesogenic (OD) or a control (CON) diet and then subsequently fed either the OD or CON diets from the onset of puberty and throughout early pregnancy. Mammary glands were collected during early pregnancy (Day 8 of pregnancy). Rabbits fed with OD milk and then subjected to an OD diet displayed an abnormal development of the mammary gland: the mammary ducts were markedly enlarged (P casein micelles. Leptin has been shown to be involved in modulating several developmental processes. We therefore analyzed its expression in the mammary gland. Mammary leptin mRNA was strongly expressed in rabbits fed with OD milk and subjected to an OD diet by comparison with the CON rabbits. Leptin transcripts and protein were localized in the epithelial cells, indicating that the increase in leptin synthesis occurs in this compartment. Taken together, these findings suggest that early-life nutritional history, in particular through the milking period, can determine subsequent mammary gland development. Moreover, they highlight the potentially important regulatory role that leptin may play during critical early-life nutritional windows with respect to long-term growth and mammary function. PMID:26020186

  16. Lipid peroxidation and apoptotic response in rat brain areas induced by long-term administration of nandrolone: the mutual crosstalk between ROS and NF-kB.

    Science.gov (United States)

    Turillazzi, Emanuela; Neri, Margherita; Cerretani, Daniela; Cantatore, Santina; Frati, Paola; Moltoni, Laura; Busardò, Francesco Paolo; Pomara, Cristoforo; Riezzo, Irene; Fineschi, Vittorio

    2016-04-01

    The aim of this study was to evaluate the played by oxidative stress in the apoptotic response in different brain areas of rats chronically treated with supra-physiological doses of nandrolone decanoate (ND). Immunohistochemical study and Western blot analysis were performed to evaluate cells' apoptosis and to measure the effects of expression of specific mediators, such as NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), Bcl-2 (B-cell lymphoma 2), SMAC/DIABLO (second mitochondria-derived activator of caspases/direct IAP-binding protein with low PI) and VMAT2 (vesicular monoamine transporter 2) on apoptosis. The results of the present study indicate that a long-term administration of ND promotes oxidative injury in rat brain specific areas. A link between oxidative stress and NF-κB signalling pathways is supported by our results. In addition to high levels of oxidative stress, we consistently observed a strong immunopositivity to NF-κB. It has been argued that one of the pathways leading to the activation of NF-κB could be under reactive oxygen species (ROS)-mediated control. In fact, growing evidence suggests that although in limited doses, endogenous ROS may play an activating role in NF-κB signalling, while above a certain threshold, they may negatively impact upon this signalling. However, a mutual crosstalk between ROS and NF-κB exists and recent studies have shown that ROS activity is subject to negative feedback regulation by NF-κB, and that this negative regulation of ROS is the means through which NF-κB counters programmed cells. PMID:26828721

  17. What Does Long-Term Care Include?

    Medline Plus

    Full Text Available Video: "What Does Long-Term Care Include?" Long-term care involves a variety of services designed to meet a person's health or personal care needs during a short or long period of ...

  18. Aircraft noise-induced annoyance in the vicinity of Cologne/Bonn Airport - The examination of short-term and long-term annoyance as well as their major determinants

    OpenAIRE

    BARTELS, SUSANNE

    2014-01-01

    In the light of a continuously growing air traffic and a presumably resulting impairment of the quality of life of airport residents, the present doctoral thesis aims at the extensive investi-gation and description of short-term and long-term annoyance induced by aircraft noise in the vicinity of Cologne/Bonn Airport, Germany. This thesis was written in the framework of the European project COSMA (Community Oriented Solutions to Minimise Aircraft noise annoyance). A telephone study with 1,262...

  19. The effect of subfornical organ lesions and ventricular blockade on drinking induced by angiotensin II.

    Science.gov (United States)

    Hoffman, W E; Phillips, M I

    1976-05-21

    The role of the subfornical organ (SFO) as the unique receptor site for the drinking behavior induced by intracranial injections of angiotensin II (AII) was investigated. It was found that: (1) drinking in response to intraventricular (IVT) injections of AII was reduced in 6 rats but was unchanged after 80-100% damage of the SFO in 4 cases; (2) reduction of drinking to lateral ventricular application of AII was seen with no apparent SFO damage in 4 rats; (3) recovery of the AII induced drinking deficit was consistently observed within a short time interval (14 days), even in those animals with complete SFO lesions: (4) the presence of ventricular debris was correlated with deficits in water intake to IVT angiotensin injections. In a second experiment artificial blockade of the ventricular space was produced by a plugging technique. Plugging the anterior third ventricle simulated the effects of SFO lesioning. It was concluded that the SFO is not a unique receptor area since the ventral anterior third ventricle is also sensitive for AII (IVT) induced drinking. If the SFO is a receptor site for AII circulating in the CSF it is probably not the only periventricular receptor site. Access of AII to the anterior ventral third ventricle appears to be essential for inducement of drinking. PMID:1276893

  20. Long-term biosignals visualization and processing

    OpenAIRE

    Gomes, Ricardo Rafael Baptista

    2011-01-01

    Long-term biosignals acquisitions are an important source of information about the patients’state and its evolution. However, long-term biosignals monitoring involves managing extremely large datasets, which makes signal visualization and processing a complex task. To overcome these problems, a new data structure to manage long-term biosignals was developed. Based on this new data structure, dedicated tools for long-term biosignals visualization and processing were implemented. A mul...

  1. CD44+/CD105+ Human Amniotic Fluid Mesenchymal Stem Cells Survive and Proliferate in the Ovary Long-Term in a Mouse Model of Chemotherapy-Induced Premature Ovarian Failure

    Directory of Open Access Journals (Sweden)

    Te Liu, Yongyi Huang, Lihe Guo, Weiwei Cheng, Gang Zou

    2012-01-01

    Full Text Available Objectives: Stem cell transplantation has been reported to rescue ovarian function in a preclinical mouse model of chemotherapy-induced premature ovarian failure (POF; however, maintaining the survival and self-renewal of transplanted seed cells in ovarian tissues over the long-term remains a troublesome issue. In this study we aimed to determine whether the CD44+/CD105+ human amniotic fluid cell (HuAFCs subpopulation represent potential seed cells for stem cell transplantation treatments in POF. Materials and methods: The CD44+/CD105+ subpopulation were isolated from HuAFCs, cultured in vitro, and injected into a cyclophosphamide-induced mouse model of POF. Results: Under continuous subculture in vitro, CD44+/CD105+ cells proliferated rapidly and expressed high levels of the proliferative markers Ki67 and survivin, as well as high levels of a number of mesenchymal stem cell biomarkers. Moreover, when red fluorescence protein (RFP-transduced CD44+/CD105+ HuAFCs were transplanted into the ovaries of POF mice, the cells could be detected by fluorescence microscopy up to three weeks after injection. Furthermore, the BrdUrd incorporation assay and immunofluorescent staining demonstrated that CD44+/CD105+ HuAFCs underwent normal cycles of cell proliferation and self-renewal in the ovarian tissues of POF mice over the long-term. Conclusions: The mesenchymal stem cell properties and long-term in vivo survival of CD44+/CD105+ HuAFCs make them ideal seed cells for stem cell transplantation to treat POF.

  2. Putative role of monoamines in the antidepressant-like mechanism induced by striatal MT2 blockade.

    Science.gov (United States)

    Noseda, Ana Carolina D; Rodrigues, Lais S; Targa, Adriano D S; Aurich, Mariana F; Vital, Maria A B F; Da Cunha, Cláudio; Lima, Marcelo M S

    2014-12-15

    It has been observed that the secretion pattern of melatonin is modified in Parkinson's disease (PD). Hence, it is hypothesized that dysregulations of melatonin MT2 receptors may be involved in the installation of depression in PD patients. Together with recent evidence based on the use of the intranigral rotenone model of PD, have led to the hypothesis that modulating the striatal MT2 receptor could provide a more comprehensive understanding of the antidepressant properties triggered. To further investigate this issue, male Wistar rats were infused with intranigral rotenone (12μg/μL) and seven days later subjected to a rapid eye movement sleep deprivation (REMSD) for 24h. After, we injected within the striatum the MT2 selective agonist, 8-M-PDOT (10μg/μL), the MT2 selective antagonist, 4-P-PDOT (5μg/μL) or vehicle. Subsequently, they were tested in the forced swimming test and were allowed to perform the sleep rebound (REB). Then, the rats were re-tested, and the striatum, hippocampus and substantia nigra pars compacta (SNpc) were collected for neurochemical purposes. Results indicated substantial antidepressant effects promoted by the blockade of striatal MT2 receptors that were potentiated by REMSD. MT2 activation increased DA levels in the striatum and hippocampus, while MT2 blockade increase DA in the SNpc. 4-P-PDOT treatment of the rotenone REMSD group generated a decrement in 5-HT levels within the striatum, hippocampus and SNpc. However, increased 5-HT turnover was observed among these structures. Therefore, we demonstrated the neurochemical antidepressant effect induced by striatal MT2 blockage associated with REMSD in the rotenone model of PD. PMID:25218873

  3. Blockade of advanced glycation end product formation attenuates bleomycin-induced pulmonary fibrosis in rats

    Directory of Open Access Journals (Sweden)

    Liu Dai-Shun

    2009-06-01

    Full Text Available Abstract Background Advanced glycation end products (AGEs have been proposed to be involved in pulmonary fibrosis, but its role in this process has not been fully understood. To investigate the role of AGE formation in pulmonary fibrosis, we used a bleomycin (BLM-stimulated rat model treated with aminoguanidine (AG, a crosslink inhibitor of AGE formation. Methods Rats were intratracheally instilled with BLM (5 mg/kg and orally administered with AG (40, 80, 120 mg/kg once daily for two weeks. AGEs level in lung tissue was determined by ELISA and pulmonary fibrosis was evaluated by Ashcroft score and hydroxyproline assay. The expression of heat shock protein 47 (HSP47, a collagen specific molecular chaperone, was measured with RT-PCR and Western blot. Moreover, TGFβ1 and its downstream Smad proteins were analyzed by Western blot. Results AGEs level in rat lungs, as well as lung hydroxyproline content and Ashcroft score, was significantly enhanced by BLM stimulation, which was abrogated by AG treatment. BLM significantly increased the expression of HSP47 mRNA and protein in lung tissues, and AG treatment markedly decreased BLM-induced HSP47 expression in a dose-dependent manner (p Conclusion These findings suggest AGE formation may participate in the process of BLM-induced pulmonary fibrosis, and blockade of AGE formation by AG treatment attenuates BLM-induced pulmonary fibrosis in rats, which is implicated in inhibition of HSP47 expression and TGFβ/Smads signaling.

  4. Ethanolic Extract of the Seed of Zizyphus jujuba var. spinosa Ameliorates Cognitive Impairment Induced by Cholinergic Blockade in Mice

    OpenAIRE

    Lee, Hyung Eun; Lee, So Young; Kim, Ju Sun; Park, Se Jin; Kim, Jong Min; Lee, Young Woo; Jung, Jun Man; Kim, Dong hyun; Shin, Bum Young; Jang, Dae Sik; Kang, Sam Sik; Ryu, Jong Hoon

    2013-01-01

    In the present study, we investigated the effect of ethanolic extract of the seed of Zizyphus jujuba var. spinosa (EEZS) on cholinergic blockade-induced memory impairment in mice. Male ICR mice were treated with EEZS. The behavioral tests were conducted using the passive avoidance, the Y-maze, and the Morris water maze tasks. EEZS (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in our present behavioral tasks without changes of locomotor activit...

  5. Sleep facilitates long-term face adaptation.

    Science.gov (United States)

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-10-22

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as 'storage'. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation--which are usually not considered to play a relevant role in mnemonic processes--with learning and memory, and at the same time reveal a new function of sleep in cognition. PMID:23986109

  6. Low-frequency stimulation induces a durable long-term depression in young adult hyperthyroid rats: the role of p38 mitogen-activated protein kinase and protein phosphatase 1.

    Science.gov (United States)

    Tan, Burak; Bitiktaş, Soner; Kavraal, Şehrazat; Dursun, Nurcan; Dönmez Altuntaş, Hamiyet; Suer, Cem

    2016-06-15

    Long-term potentiation and long-term depression (LTD) are cellular mechanisms of learning and memory in the mammalian brain. We have previously shown that adult hyperthyroid rats showed a delay in the acquisition of a place learning task and attenuated long-term potentiation. However, changes in LTD in hyperthyroidism remain unclear. Rats were administered 0.2 mg/kg/day of L-thyroxine for 21 days starting at postnatal day 40 to induce hyperthyroidism. LTD was induced in the dentate gyrus using low-frequency stimulation (LFS) of the perforant pathway. The mRNA expressions of p38 mitogen-activated protein kinase (p38-MAPK) and protein phosphatase 1 (PP1) were evaluated using a quantitative reverse transcriptase PCR. In control rats, a standard LFS protocol induced a slight depression of the population spike (PS) amplitude during the induction phase of LTD (76±13% vs. baseline), but a small potentiation of the PS amplitude was observed in the early (107±18%) and late (111±20%) phases of LTD. Interestingly, in the hyperthyroid rats, the same LFS protocol induced a reliable LTD in the dentate gyrus of the hippocampus as evidenced by a marked depression in the PS amplitude during the induction (54±6% vs. baseline) and the early phases (56±8%) of LTD. Elevated mRNA levels of p38-MAPK and PP1 were observed in the hippocampus of the LFS-treated hyperthyroid rats compared with the hippocampus of the vehicle-treated hyperthyroid rats. No significant change in p38-MAPK or PP1 mRNA expression was observed in the euthyroid rats. The present study shows that a standard LFS protocol can induce a durable depression of synaptic strength and an upregulation of PP1 and p38-MAPK mRNA in hyperthyroid rats. We conclude that hyperthyroidism can induce molecular changes associated with degeneration of the hippocampus. The relationship between the levels of thyroid hormone and dementia requires further investigation. PMID:27128724

  7. Training-induced changes in muscle CSA, muscle strength, EMG, and rate of force development in elderly subjects after long-term unilateral disuse

    DEFF Research Database (Denmark)

    Suetta, Charlotte; Aagaard, Per; Rosted, Anna;

    2004-01-01

    The ability to develop muscle force rapidly may be a very important factor to prevent a fall and to perform other tasks of daily life. However, information is still lacking on the range of training-induced neuromuscular adaptations in elderly humans recovering from a period of disuse. Therefore, ...

  8. TNF-α blockade induces IL-10 expression in human CD4+ T cells

    Science.gov (United States)

    Evans, Hayley G.; Roostalu, Urmas; Walter, Gina J.; Gullick, Nicola J.; Frederiksen, Klaus S.; Roberts, Ceri A.; Sumner, Jonathan; Baeten, Dominique L.; Gerwien, Jens G.; Cope, Andrew P.; Geissmann, Frederic; Kirkham, Bruce W.; Taams, Leonie S.

    2014-02-01

    IL-17+ CD4+ T (Th17) cells contribute to the pathogenesis of several human inflammatory diseases. Here we demonstrate that TNF inhibitor (TNFi) drugs induce the anti-inflammatory cytokine IL-10 in CD4+ T cells including IL-17+ CD4+ T cells. TNFi-mediated induction of IL-10 in IL-17+ CD4+ T cells is Treg-/Foxp3-independent, requires IL-10 and is overcome by IL-1β. TNFi-exposed IL-17+ CD4+ T cells are molecularly and functionally distinct, with a unique gene signature characterized by expression of IL10 and IKZF3 (encoding Aiolos). We show that Aiolos binds conserved regions in the IL10 locus in IL-17+ CD4+ T cells. Furthermore, IKZF3 and IL10 expression levels correlate in primary CD4+ T cells and Aiolos overexpression is sufficient to drive IL10 in these cells. Our data demonstrate that TNF-α blockade induces IL-10 in CD4+ T cells including Th17 cells and suggest a role for the transcription factor Aiolos in the regulation of IL-10 in CD4+ T cells.

  9. Blockade of IL-36 receptor signaling does not prevent from TNF-induced arthritis.

    Directory of Open Access Journals (Sweden)

    Anja Derer

    Full Text Available INTRODUCTION: Interleukin (IL-36α is a newly described member of the IL-1 cytokine family with a known inflammatory and pathogenic function in psoriasis. Recently, we could demonstrate that the receptor (IL-36R, its ligand IL-36α and its antagonist IL-36Ra are expressed in synovial tissue of arthritis patients. Furthermore, IL-36α induces MAP-kinase and NFκB signaling in human synovial fibroblasts with subsequent expression and secretion of pro-inflammatory cytokines. METHODS: To understand the pathomechanism of IL-36 dependent inflammation, we investigated the biological impact of IL-36α signaling in the hTNFtg mouse. Also the impact on osteoclastogenesis by IL-36α was tested in murine and human osteoclast assays. RESULTS: Diseased mice showed an increased expression of IL-36R and IL-36α in inflamed knee joints compared to wildtype controls. However, preventively treating mice with an IL-36R blocking antibody led to no changes in clinical onset and pattern of disease. Furthermore, blockade of IL-36 signaling did not change histological signs of TNF-induced arthritis. Additionally, no alteration on bone homeostasis was observed in ex vivo murine and human osteoclast differentiation assays. CONCLUSION: Thus we conclude that IL-36α does not affect the development of inflammatory arthritis.

  10. A long-term three dimensional liver co-culture system for improved prediction of clinically relevant drug-induced hepatotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Kostadinova, Radina; Boess, Franziska [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland); Applegate, Dawn [RegeneMed, 9855 Towne Centre Drive Suite 200, San Diego, CA 92121 (United States); Suter, Laura; Weiser, Thomas; Singer, Thomas [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland); Naughton, Brian [RegeneMed, 9855 Towne Centre Drive Suite 200, San Diego, CA 92121 (United States); Roth, Adrian, E-mail: adrian_b.roth@roche.com [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland)

    2013-04-01

    Drug-induced liver injury (DILI) is the major cause for liver failure and post-marketing drug withdrawals. Due to species-specific differences in hepatocellular function, animal experiments to assess potential liabilities of drug candidates can predict hepatotoxicity in humans only to a certain extent. In addition to animal experimentation, primary hepatocytes from rat or human are widely used for pre-clinical safety assessment. However, as many toxic responses in vivo are mediated by a complex interplay among different cell types and often require chronic drug exposures, the predictive performance of hepatocytes is very limited. Here, we established and characterized human and rat in vitro three-dimensional (3D) liver co-culture systems containing primary parenchymal and non-parenchymal hepatic cells. Our data demonstrate that cells cultured on a 3D scaffold have a preserved composition of hepatocytes, stellate, Kupffer and endothelial cells and maintain liver function for up to 3 months, as measured by the production of albumin, fibrinogen, transferrin and urea. Additionally, 3D liver co-cultures maintain cytochrome P450 inducibility, form bile canaliculi-like structures and respond to inflammatory stimuli. Upon incubation with selected hepatotoxicants including drugs which have been shown to induce idiosyncratic toxicity, we demonstrated that this model better detected in vivo drug-induced toxicity, including species-specific drug effects, when compared to monolayer hepatocyte cultures. In conclusion, our results underline the importance of more complex and long lasting in vitro cell culture models that contain all liver cell types and allow repeated drug-treatments for detection of in vivo-relevant adverse drug effects. - Highlights: ► 3D liver co-cultures maintain liver specific functions for up to three months. ► Activities of Cytochrome P450s remain drug- inducible accross three months. ► 3D liver co-cultures recapitulate drug-induced liver toxicity

  11. A long-term three dimensional liver co-culture system for improved prediction of clinically relevant drug-induced hepatotoxicity

    International Nuclear Information System (INIS)

    Drug-induced liver injury (DILI) is the major cause for liver failure and post-marketing drug withdrawals. Due to species-specific differences in hepatocellular function, animal experiments to assess potential liabilities of drug candidates can predict hepatotoxicity in humans only to a certain extent. In addition to animal experimentation, primary hepatocytes from rat or human are widely used for pre-clinical safety assessment. However, as many toxic responses in vivo are mediated by a complex interplay among different cell types and often require chronic drug exposures, the predictive performance of hepatocytes is very limited. Here, we established and characterized human and rat in vitro three-dimensional (3D) liver co-culture systems containing primary parenchymal and non-parenchymal hepatic cells. Our data demonstrate that cells cultured on a 3D scaffold have a preserved composition of hepatocytes, stellate, Kupffer and endothelial cells and maintain liver function for up to 3 months, as measured by the production of albumin, fibrinogen, transferrin and urea. Additionally, 3D liver co-cultures maintain cytochrome P450 inducibility, form bile canaliculi-like structures and respond to inflammatory stimuli. Upon incubation with selected hepatotoxicants including drugs which have been shown to induce idiosyncratic toxicity, we demonstrated that this model better detected in vivo drug-induced toxicity, including species-specific drug effects, when compared to monolayer hepatocyte cultures. In conclusion, our results underline the importance of more complex and long lasting in vitro cell culture models that contain all liver cell types and allow repeated drug-treatments for detection of in vivo-relevant adverse drug effects. - Highlights: ► 3D liver co-cultures maintain liver specific functions for up to three months. ► Activities of Cytochrome P450s remain drug- inducible accross three months. ► 3D liver co-cultures recapitulate drug-induced liver toxicity

  12. Adenoviral-mediated localized CTLA-4Ig gene expression induces long-term allograft pancreas survival and donor-specific immune tolerance in rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    T cell activation following alloantigen recognition plays a critical role in the development of the rejection in all solid organ, tissue and cell transplantation. A recombinant molecule, cytotoxic T lymphocyte antigen 4 antibody (CTLA-4Ig), is known to induce to T-cell into "anergy" by blocking the costimulatory B7-CD28 interaction. Either systemic or localized administration of CTLA-Ig has been shown to prolong allograft survival and induce donor-specific tolerance in some transplant models. In this study, we characterized the expression and immunosuppressive effectiveness of adenoviral-mediated CTLA-4Ig gene transfer. We demonstrated transduction of the allografts with AdCTLA-41g resulted in localized expression, permanent graft survival and stable donor-specific tolerance. In addition, by performing simultaneous dual-organ transplantation, we targeted on immunosuppression through a local expression of CTLA-4Ig via adenoviral-mediated gene transfer into pancreatic allografts.

  13. Critical Role of Endoplasmic Reticulum Stress in Chronic Intermittent Hypoxia-Induced Deficits in Synaptic Plasticity and Long-Term Memory

    OpenAIRE

    Xu, Lin-Hao; Xie, Hui; Shi, Zhi-Hui; Du, Li-Da; Wing, Yun-Kwok; Li, Albert M.; Ke, Ya; Yung, Wing-Ho

    2015-01-01

    Aims: This study examined the role of endoplasmic reticulum (ER) stress in mediating chronic intermittent hypoxia (IH)-induced neurocognitive deficits. We designed experiments to demonstrate that ER stress is initiated in the hippocampus under chronic IH and determined its role in apoptotic cell death, impaired synaptic structure and plasticity, and memory deficits. Results: Two weeks of IH disrupted ER fine structure and upregulated ER stress markers, glucose-regulated protein 78, caspase-12...

  14. Long-term effects of acupuncture treatment on airway smooth muscle in a rat model of smoke-induced chronic obstructive pulmonary disease

    Science.gov (United States)

    Li, Jia; Wu, Song; Tang, Hongtu; Huang, Wei; Wang, Lushan; Zhou, Huanjiao; Zhou, Miao; Wang, Hua; Li, Jing

    2016-01-01

    Background Chronic obstructive pulmonary disease (COPD) is one of the most common lung diseases. It is a chronic inflammatory process characterised by airway obstruction and progressive lung inflammation, associated with difficulty breathing and insensitivity to corticosteroid therapy. Although there is some preliminary evidence to suggest a beneficial effect of acupuncture on COPD, its mechanism of action has not been investigated. Our aim was to examine the anti-inflammatory effects of acupuncture in a rat model of COPD induced by exposure to cigarette smoke (CS). Methods Sixty Sprague–Dawley rats were exposed to the smoke of 15 cigarettes for 1 h/day, 6 days/week for 3 months to induce COPD and treated with acupuncture at BL13 (Feishu), BL23 (Shenshu) and Dingchuan (COPD+Acupuncture, n=15), sham acupuncture (COPD+Sham, n=15) or left untreated (n=15). Exposed rats were compared with controls not exposed to CS (control, n=15). Pulmonary function was measured, and tumour necrosis factor-α (TNF-α) and interleukin-8 (IL-8) levels were determined in bronchoalveolar lavage fluid by ELISA. Histone deacetylase 2 (HDAC2) protein and mRNA expression were examined in lung tissue and in bronchus. Results Acupuncture treatment appeared to protect pulmonary function and reduce the COPD-induced inflammatory response by decreasing cell inflammation and the production of TNF-α and IL-8. Acupuncture also enhanced HDAC2 mRNA and protein expression, suggesting a possible direct effect on protein structure through post-translational modifications. Conclusions Our results suggest that acupuncture regulates inflammatory cytokines and contributes to lung protection in a rat model of smoke-induced COPD by modulating HDAC2. PMID:26345700

  15. Immediate Epileptogenesis after Kainate-Induced Status Epilepticus in C57BL/6J Mice: Evidence from Long Term Continuous Video-EEG Telemetry.

    Directory of Open Access Journals (Sweden)

    Sreekanth Puttachary

    Full Text Available The C57BL/6J mouse as a model of seizure/epilepsy is challenging due to high mortality and huge variability in response to kainate. We have recently demonstrated that repeated administration of a low dose of kainate by intraperitoneal route can induce severe status epilepticus (SE with 94% survival rate. In the present study, based on continuous video-EEG recording for 4-18 weeks from epidurally implanted electrodes on the cortex, we demonstrate that this method also induces immediate epileptogenesis (<1-5 days post-SE. This finding was based on identification of two types of spontaneous recurrent seizures; behavioral convulsive seizures (CS and electrographic nonconvulsive seizures (NCS. The identification of the spontaneous CS, stage 3-5 types, was based on the behaviors (video that were associated with the EEG characteristics (stage 3-5 epileptiform spikes, the power spectrum, and the activity counts. The electrographic NCS identification was based on the stage 1-2 epileptiform spike clusters on the EEG and their associated power spectrum. Severe SE induced immediate epileptogenesis in all the mice. The maximum numbers of spontaneous CS were observed during the first 4-6 weeks of the SE and they decreased thereafter. Mild SE also induced immediate epileptogenesis in some mice but the CS were less frequent. In both the severe and the mild SE groups, the spontaneous electrographic NCS persisted throughout the 18 weeks observation period, and therefore this could serve as a chronic model for complex seizures. However, unlike rat kainate models, the C57BL/6J mouse kainate model is a unique regressive CS model of epilepsy. Further studies are required to understand the mechanism of recovery from spontaneous CS in this model, which could reveal novel therapeutic targets for epilepsy.

  16. Long-Term Aerobic Exercise Protects against Cisplatin-Induced Nephrotoxicity by Modulating the Expression of IL-6 and HO-1

    OpenAIRE

    Miyagi, Mariana Yasue Saito; Seelaender, Marilia; Castoldi, Angela; de Almeida, Danilo Candido; Bacurau, Aline Villa Nova; Andrade-Oliveira, Vinicius; Enjiu, Lucas Maceratesi; Pisciottano, Marcus; Hayashida, Caroline Yuri; Hiyane, Meire Ioshie; Brum, Patricia Chakur; Camara, Niels Olsen Saraiva; Amano, Mariane Tami

    2014-01-01

    Nephrotoxicity is substantial side effect for 30% of patients undergoing cancer therapy with cisplatin and may force them to change or even abandon the treatment. Studies regarding aerobic exercise have shown its efficacy for the treatment of many types of diseases and its capacity to reduce tumors. However, little is known about the impact of physical exercise on cisplatin-induced acute kidney injury (AKI). In the present study, our aim was to investigate the role of physical exercise in AKI...

  17. Long-term aerobic exercise protects against cisplatin-induced nephrotoxicity by modulating the expression of IL-6 and HO-1.

    Directory of Open Access Journals (Sweden)

    Mariana Yasue Saito Miyagi

    Full Text Available Nephrotoxicity is substantial side effect for 30% of patients undergoing cancer therapy with cisplatin and may force them to change or even abandon the treatment. Studies regarding aerobic exercise have shown its efficacy for the treatment of many types of diseases and its capacity to reduce tumors. However, little is known about the impact of physical exercise on cisplatin-induced acute kidney injury (AKI. In the present study, our aim was to investigate the role of physical exercise in AKI induced by cisplatin. We submitted C57Bl6 male mice to seven weeks of chronic exercise on a training treadmill and treated them with single i.p. injection of cisplatin (20 mg/kg in the last week. Exercise efficacy was confirmed by an increased capillary-to-fiber ratio in the gastrocnemius muscle of exercised groups (EX and CIS-EX. The group submitted to exercise before cisplatin administration (CIS-EX exhibited less weight loss and decreased serum urea levels compared to the cisplatin group (CIS. Exercise also showed a protective role against cisplatin-induced cell death in the kidney. The CIS-EX group showed a lower inflammatory response, with less TNF and IL-10 expression in the kidney and serum. In the same group, we observed an increase of IL-6 and HO-1 expression in the kidney. Taken together, our results indicate that chronic aerobic exercise is able to attenuate AKI by inducing IL-6 and HO-1 production, which results in lower inflammatory and apoptotic profiles in the kidney.

  18. Glucose intolerance induced by blockade of central FGF receptors is linked to an acute stress response

    Science.gov (United States)

    Rojas, Jennifer M.; Matsen, Miles E.; Mundinger, Thomas O.; Morton, Gregory J.; Stefanovski, Darko; Bergman, Richard N.; Kaiyala, Karl J.; Taborsky, Gerald J.; Schwartz, Michael W.

    2015-01-01

    Objective Central administration of ligands for fibroblast growth factor receptors (FGFRs) such as fibroblast growth factor-19 (FGF19) and FGF21 exert glucose-lowering effects in rodent models of obesity and type 2 diabetes (T2D). Conversely, intracerebroventricular (icv) administration of the non-selective FGFR inhibitor (FGFRi) PD173074 causes glucose intolerance, implying a physiological role for neuronal FGFR signaling in glucose homeostasis. The current studies were undertaken to identify neuroendocrine mechanisms underlying the glucose intolerance induced by pharmacological blockade of central FGFRs. Methods Overnight fasted, lean, male, Long-Evans rats received icv injections of either PD173074 or vehicle (Veh) followed 30 min later by performance of a frequently sampled intravenous glucose tolerance test (FSIGT). Minimal model analysis of glucose and insulin data from the FSIGT was performed to estimate insulin-dependent and insulin-independent components of glucose disposal. Plasma levels of lactate, glucagon, corticosterone, non-esterified free fatty acids (NEFA) and catecholamines were measured before and after intravenous (iv) glucose injection. Results Within 20 min of icv PD173074 injection (prior to the FSIGT), plasma levels of lactate, norepinephrine and epinephrine increased markedly, and each returned to baseline rapidly (within 8 min) following the iv glucose bolus. In contrast, plasma glucagon levels were not altered by icv FGFRi at either time point. Consistent with a previous report, glucose tolerance was impaired following icv PD173074 compared to Veh injection and, based on minimal model analysis of FSIGT data, this effect was attributable to reductions of both insulin secretion and the basal insulin effect (BIE), consistent with the inhibitory effect of catecholamines on pancreatic β-cell secretion. By comparison, there were no changes in glucose effectiveness at zero insulin (GEZI) or the insulin sensitivity index (SI). To determine if

  19. Testing mechanisms of N-enrichment-induced species loss in a semiarid Inner Mongolia grassland: critical thresholds and implications for long-term ecosystem responses.

    Science.gov (United States)

    Lan, Zhichun; Bai, Yongfei

    2012-11-19

    The increase in nutrient availability as a consequence of elevated nitrogen (N) deposition is an important component of global environmental change. This is likely to substantially affect the functioning and provisioning of ecosystem services by drylands, where water and N are often limited. We tested mechanisms of chronic N-enrichment-induced plant species loss in a 10-year field experiment with six levels of N addition rate. Our findings on a semi-arid grassland in Inner Mongolia demonstrated that: (i) species richness (SR) declined by 16 per cent even at low levels of additional N (1.75 g N m(-2) yr(-1)), and 50-70% species were excluded from plots which received high N input (10.5-28 g N m(-2) yr(-1)); (ii) the responses of SR and above-ground biomass (AGB) to N were greater in wet years than dry years; (iii) N addition increased the inter-annual variations in AGB, reduced the drought resistance of production and hence diminished ecosystem stability; (iv) the critical threshold for chronic N-enrichment-induced reduction in SR differed between common and rare species, and increased over the time of the experiment owing to the loss of the more sensitive species. These results clearly indicate that both abundance and functional trait-based mechanisms operate simultaneously on N-induced species loss. The low initial abundance and low above-ground competitive ability may be attributable to the loss of rare species. However, shift from below-ground competition to above-ground competition and recruitment limitation are likely to be the key mechanisms for the loss of abundant species, with soil acidification being less important. Our results have important implications for understanding the impacts of N deposition and global climatic change (e.g. change in precipitation regimes) on biodiversity and ecosystem services of the Inner Mongolian grassland and beyond. PMID:23045710

  20. A neuroligin-1-derived peptide stimulates phosphorylation of the NMDA receptor NR1 subunit and rescues MK-801-induced decrease in long-term potentiation and memory impairment

    DEFF Research Database (Denmark)

    Korshunova, Irina; Gjørlund, Michelle D; Jacobsen, Sylwia Owczarek;

    2015-01-01

    , neurolide-2, reduces sociability and increase animal aggression. We hypothesized that interfering with NL1 function at the excitatory synapses might regulate synaptic plasticity and learning, and counteract memory deficits induced by N-methyl-d-aspartate (NMDA) receptor inhibition. First, neuronal NMDA...... site important for synaptic trafficking, potentially favoring synaptic receptor retention. Our findings emphasize the role of NL1-NMDA receptor interaction in cognition, and identify neurolide-1, as a valuable pharmacological tool to examine the in vivo role of postsynaptic NL1 in cognitive behavior in...

  1. Long-term high-fat-diet feeding induces skeletal muscle mitochondrial biogenesis in rats in a sex-dependent and muscle-type specific manner

    Directory of Open Access Journals (Sweden)

    Gómez-Pérez Yolanda

    2012-02-01

    Full Text Available Abstract Background Mitochondrial dysfunction is thought to play a crucial role in the etiology of insulin resistance, in which skeletal muscle is the main tissue contributor. Sex differences in skeletal muscle insulin and antioxidant responses to high-fat-diet (HFD feeding have been described. The aim of this study was to elucidate whether there is a sex dimorphism in the effects of HFD feeding on skeletal muscle mitochondrial biogenesis and on the adiponectin signaling pathway, as well as the influence of the muscle type (oxidative or glycolytic. Methods Gastrocnemius and soleus muscles of male and female Wistar rats of 2 months of age fed with a high-fat-diet (HFD or a low fat diet for 26 weeks were used. Mitochondrial biogenesis and oxidative damage markers, oxidative capacity and antioxidant defences were analyzed. Serum insulin sensitivity parameters and the levels of proteins involved in adiponectin signaling pathway were also determined. Results HFD feeding induced mitochondrial biogenesis in both sexes, but to a higher degree in male rats. Although HFD female rats showed greater antioxidant protection and maintained a better insulin sensitivity profile than their male counterparts, both sexes showed an impaired response to adiponectin, which was more evident in gastrocnemius muscle. Conclusions We conclude that HFD rats may induce skeletal muscle mitochondrial biogenesis as an attempt to compensate the deleterious consequences of adiponectin and insulin resistance on oxidative metabolism, and that the effects of HFD feeding are sex-dependent and muscle-type specific.

  2. Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection.

    Science.gov (United States)

    Bohannon, Caitlin; Powers, Ryan; Satyabhama, Lakshmipriyadarshini; Cui, Ang; Tipton, Christopher; Michaeli, Miri; Skountzou, Ioanna; Mittler, Robert S; Kleinstein, Steven H; Mehr, Ramit; Lee, Francis Eun-Yun; Sanz, Ignacio; Jacob, Joshy

    2016-01-01

    Long-lived plasma cells are critical to humoral immunity as a lifelong source of protective antibodies. Antigen-activated B cells-with T-cell help-undergo affinity maturation within germinal centres and persist as long-lived IgG plasma cells in the bone marrow. Here we show that antigen-specific, induced IgM plasma cells also persist for a lifetime. Unlike long-lived IgG plasma cells, which develop in germinal centres and then home to the bone marrow, IgM plasma cells are primarily retained within the spleen and can develop even in the absence of germinal centres. Interestingly, their expressed IgV loci exhibit somatic mutations introduced by the activation-induced cytidine deaminase (AID). However, these IgM plasma cells are probably not antigen-selected, as replacement mutations are spread through the variable segment and not enriched within the CDRs. Finally, antibodies from long-lived IgM plasma cells provide protective host immunity against a lethal virus challenge. PMID:27270306

  3. Long-term daily vibration exposure alters current perception threshold (CPT) sensitivity and myelinated axons in a rat-tail model of vibration-induced injury.

    Science.gov (United States)

    Krajnak, Kristine; Raju, Sandya G; Miller, G Roger; Johnson, Claud; Waugh, Stacey; Kashon, Michael L; Riley, Danny A

    2016-01-01

    Repeated exposure to hand-transmitted vibration through the use of powered hand tools may result in pain and progressive reductions in tactile sensitivity. The goal of the present study was to use an established animal model of vibration-induced injury to characterize changes in sensory nerve function and cellular mechanisms associated with these alterations. Sensory nerve function was assessed weekly using the current perception threshold test and tail-flick analgesia test in male Sprague-Dawley rats exposed to 28 d of tail vibration. After 28 d of exposure, Aβ fiber sensitivity was reduced. This reduction in sensitivity was partly attributed to structural disruption of myelin. In addition, the decrease in sensitivity was also associated with a reduction in myelin basic protein and 2',3'- cyclic nucleotide phosphodiasterase (CNPase) staining in tail nerves, and an increase in circulating calcitonin gene-related peptide (CGRP) concentrations. Changes in Aβ fiber sensitivity and CGRP concentrations may serve as early markers of vibration-induced injury in peripheral nerves. It is conceivable that these markers may be utilized to monitor sensorineural alterations in workers exposed to vibration to potentially prevent additional injury. PMID:26852665

  4. Promoting long-term survival of insulin-producing cell grafts that differentiate from adipose tissue-derived stem cells to cure type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Shuzi Zhang

    Full Text Available BACKGROUND: Insulin-producing cell clusters (IPCCs have recently been generated in vitro from adipose tissue-derived stem cells (ASCs to circumvent islet shortage. However, it is unknown how long they can survive upon transplantation, whether they are eventually rejected by recipients, and how their long-term survival can be induced to permanently cure type 1 diabetes. IPCC graft survival is critical for their clinical application and this issue must be systematically addressed prior to their in-depth clinical trials. METHODOLOGY/PRINCIPAL FINDINGS: Here we found that IPCC grafts that differentiated from murine ASCs in vitro, unlike their freshly isolated islet counterparts, did not survive long-term in syngeneic mice, suggesting that ASC-derived IPCCs have intrinsic survival disadvantage over freshly isolated islets. Indeed, β cells retrieved from IPCC syngrafts underwent faster apoptosis than their islet counterparts. However, blocking both Fas and TNF receptor death pathways inhibited their apoptosis and restored their long-term survival in syngeneic recipients. Furthermore, blocking CD40-CD154 costimulation and Fas/TNF signaling induced long-term IPCC allograft survival in overwhelming majority of recipients. Importantly, Fas-deficient IPCC allografts exhibited certain immune privilege and enjoyed long-term survival in diabetic NOD mice in the presence of CD28/CD40 joint blockade while their islet counterparts failed to do so. CONCLUSIONS/SIGNIFICANCE: Long-term survival of ASC-derived IPCC syngeneic grafts requires blocking Fas and TNF death pathways, whereas blocking both death pathways and CD28/CD40 costimulation is needed for long-term IPCC allograft survival in diabetic NOD mice. Our studies have important clinical implications for treating type 1 diabetes via ASC-derived IPCC transplantation.

  5. Catecholamine and insulin control of lipolysis in subcutaneous adipose tissue during long-term diet-induced weight loss in obese women

    DEFF Research Database (Denmark)

    Koppo, Katrien; Siklová-Vitková, Michaela; Klimcáková, Eva;

    2012-01-01

    The aim of this study was to investigate the evolution of the adrenergic and insulin-mediated regulation of lipolysis during different phases of a 6-mo dietary intervention. Eight obese women underwent a 6-mo dietary intervention consisting of a 1-mo very low-calorie diet (VLCD) followed by a 2-mo...... low-calorie diet (LCD) and 3-mo weight maintenance (WM) diet. At each phase of the dietary intervention, microdialysis of subcutaneous adipose tissue (SCAT) was performed at rest and during a 3-h hyperinsulinemic euglycemic clamp. Responses of dialysate glycerol concentration (DGC) were determined at...... baseline and during local perfusions with adrenaline or adrenaline and phentolamine before and during the last 30 min of the clamp. Dietary intervention induced a body weight reduction and an improved insulin sensitivity. DGC progressively decreased during the clamp, and this decrease was similar during...

  6. Decrease in long-term marrow repopulating capacity seen after transplantation is not the result of irradiation-induced stromal injury

    International Nuclear Information System (INIS)

    Marrow cells from nonirradiated F1-W/Wv mice repopulated slightly less well than cells from lethally irradiated recipients. Therefore, avoiding irradiation of recipients did not improve the relative repopulating ability of their marrow cells. In other experiments, F1-W/Wv mice were transplanted by parabiosis with marrow of WBB6F1-+/+ (F1-+/+) mice, avoiding cellular handling and irradiation. Marrow cells transplanted to F1-W/Wv mice by this procedure demonstrated slightly better repopulating ability than did marrow cells transplanted by injection. However, they performed no better than those transplanted by parabiosis to irradiated F1-+/+ recipients. Significant impairment of stromal function after irradiation was not indicated. Apparently, stem cell damage caused by transplantation may have greater importance in causing loss of stem cell replicative potential than effects of irradiation-induced stromal injury

  7. Long-Term Boron-Excess-Induced Alterations of Gene Profiles in Roots of Two Citrus Species Differing in Boron-Tolerance Revealed by cDNA-AFLP

    Science.gov (United States)

    Guo, Peng; Qi, Yi-Ping; Yang, Lin-Tong; Ye, Xin; Huang, Jing-Hao; Chen, Li-Song

    2016-01-01

    Boron (B) toxicity is observed in some citrus orchards in China. However, limited data are available on the molecular mechanisms of citrus B-toxicity and B-tolerance. Using cDNA-AFLP, we identified 20 up- and 52 down-regulated genes, and 44 up- and 66 down-regulated genes from excess B-treated Citrus sinensis and Citrus grandis roots, respectively, thereby demonstrating that gene expression profiles were more affected in the latter. In addition, phosphorus and total soluble protein concentrations were lowered only in excess B-treated C. grandis roots. Apparently, C. sinensis had higher B-tolerance than C. grandis. Our results suggested that the following several aspects were responsible for the difference in the B-tolerance between the two citrus species including: (a) B-excess induced Root Hair Defective 3 expression in C. sinensis roots, and repressed villin4 expression in C. grandis roots; accordingly, root growth was less inhibited by B-excess in the former; (b) antioxidant systems were impaired in excess B-treated C. grandis roots, hence accelerating root senescence; (c) genes related to Ca2+ signals were inhibited (induced) by B-excess in C. grandis (C. sinensis) roots. B-excess-responsive genes related to energy (i.e., alternative oxidase and cytochrome P450), lipid (i.e., Glycerol-3-phosphate acyltransferase 9 and citrus dioxygenase), and nucleic acid (i.e., HDA19, histone 4, and ribonucleotide reductase RNR1 like protein) metabolisms also possibly accounted for the difference in the B-tolerance between the two citrus species. These data increased our understanding of the mechanisms on citrus B-toxicity and B-tolerance at transcriptional level. PMID:27446128

  8. CXCR3 blockade protects against Listeria monocytogenes infection-induced fetal wastage.

    Science.gov (United States)

    Chaturvedi, Vandana; Ertelt, James M; Jiang, Tony T; Kinder, Jeremy M; Xin, Lijun; Owens, Kathryn J; Jones, Helen N; Way, Sing Sing

    2015-04-01

    Mammalian pregnancy requires protection against immunological rejection of the developing fetus bearing discordant paternal antigens. Immune evasion in this developmental context entails silenced expression of chemoattractant proteins (chemokines), thereby preventing harmful immune cells from penetrating the maternal-fetal interface. Here, we demonstrate that fetal wastage triggered by prenatal Listeria monocytogenes infection is driven by placental recruitment of CXCL9-producing inflammatory neutrophils and macrophages that promote infiltration of fetal-specific T cells into the decidua. Maternal CD8+ T cells with fetal specificity upregulated expression of the chemokine receptor CXCR3 and, together with neutrophils and macrophages, were essential for L. monocytogenes-induced fetal resorption. Conversely, decidual accumulation of maternal T cells with fetal specificity and fetal wastage were extinguished by CXCR3 blockade or in CXCR3-deficient mice. Remarkably, protection against fetal wastage and in utero L. monocytogenes invasion was maintained even when CXCR3 neutralization was initiated after infection, and this protective effect extended to fetal resorption triggered by partial ablation of immune-suppressive maternal Tregs, which expand during pregnancy to sustain fetal tolerance. Together, our results indicate that functionally overriding chemokine silencing at the maternal-fetal interface promotes the pathogenesis of prenatal infection and suggest that therapeutically reinforcing this pathway represents a universal approach for mitigating immune-mediated pregnancy complications. PMID:25751061

  9. Angiotensin II (AT1) Receptor Blockade Reduces Vascular Tissue Factor in Angiotensin II-Induced Cardiac Vasculopathy

    OpenAIRE

    Dominik N Müller; Mervaala, Eero M A; Dechend, Ralf; Fiebeler, Anette; Park, Joon-Keun; Schmidt, Folke; Theuer, Jürgen; Breu, Volker; Mackman, Nigel; Luther, Thomas; Schneider, Wolfgang; Gulba, Dietrich; Ganten, Detlev; Haller, Hermann; Luft, Friedrich C.

    2000-01-01

    Tissue factor (TF), a main initiator of clotting, is up-regulated in vasculopathy. We tested the hypothesis that chronic in vivo angiotensin (ANG) II receptor AT1 receptor blockade inhibits TF expression in a model of ANG II-induced cardiac vasculopathy. Furthermore, we explored the mechanisms by examining transcription factor activation and analyzing the TF promoter. Untreated transgenic rats overexpressing the human renin and angiotensinogen genes (dTGR) feature hypertension and severe left...

  10. Transforming growth factor-β inhibition and endothelin receptor blockade in rats with monocrotaline-induced pulmonary hypertension

    OpenAIRE

    Megalou, Aikaterini J; Glava, Chryssoula; Vilaeti, Agapi D.; Oikonomidis, Dimitrios L; Baltogiannis, Giannis G.; Papalois, Apostolos; Vlahos, Antonios P.; Kolettis, Theofilos M

    2012-01-01

    Transforming growth factor-β (TGF-β) inhibition is an investigational therapy for pulmonary arterial hypertension with promising results in experimental studies. The present work compared this approach with endothelin-receptor blockade and evaluated the effects of combined administration. Pulmonary arterial hypertension was induced by single monocrotaline injection (60 mg/kg) in 75 Wistar rats and 15 rats served as controls. Intervention groups consisted of treatment with an antibody against ...

  11. Long-term decrease in Na+,K+-ATPase activity after pilocarpine-induced status epilepticus is associated with nitration of its alpha subunit.

    Science.gov (United States)

    Funck, Vinícius Rafael; Ribeiro, Leandro Rodrigo; Pereira, Letícia Meier; de Oliveira, Clarissa Vasconcelos; Grigoletto, Jéssica; Fighera, Michele Rechia; Royes, Luiz Fernando Freire; Furian, Ana Flávia; Oliveira, Mauro Schneider

    2014-12-01

    Temporal lobe epilepsy (TLE) is the most common type of epilepsy with about one third of TLE patients being refractory to antiepileptic drugs. Knowledge about the mechanisms underlying seizure activity is fundamental to the discovery of new drug targets. Brain Na(+),K(+)-ATPase activity contributes to the maintenance of the electrochemical gradients underlying neuronal resting and action potentials as well as the uptake and release of neurotransmitters. In the present study we tested the hypothesis that decreased Na(+),K(+)-ATPase activity is associated with changes in the alpha subunit phosphorylation and/or redox state. Activity of Na(+),K(+)-ATPase decreased in the hippocampus of C57BL/6 mice 60 days after pilocarpine-induced status epilepticus (SE). In addition, the Michaelis-Menten constant for ATP of α2/3 isoforms increased at the same time point. Nitration of the α subunit may underlie decreased Na(+),K(+)-ATPase activity, however no changes in expression or phosphorylation state at Ser(943) were found. Further studies are necessary define the potential of nitrated Na(+),K(+)-ATPase as a new therapeutic target for seizure disorders. PMID:25311690

  12. Long-term exposure to cypermethrin and piperonyl butoxide cause liver and kidney inflammation and induce genotoxicity in New Zealand white male rabbits.

    Science.gov (United States)

    Vardavas, Alexander I; Stivaktakis, Polychronis D; Tzatzarakis, Manolis N; Fragkiadaki, Persefoni; Vasilaki, Fotini; Tzardi, Maria; Datseri, Galateia; Tsiaoussis, John; Alegakis, Athanasios K; Tsitsimpikou, Christina; Rakitskii, Valerii N; Carvalho, Félix; Tsatsakis, Aristidis M

    2016-08-01

    Cypermethrin (CY) is a frequently used class II pyrethroid pesticide, while piperonyl butoxide (PBO) plays a major role in the pesticide formulation of synthetic pyrethroids. Synthetic pyrethroids are metabolized in mammals via oxidation and ester hydrolysis. PBO can prevent the metabolism of CY and enhances its pesticide effect. While this potentiation effect reduces the amount of pesticide required to eliminate insects, it is not clear how this mixture affects mammals. In our in vivo experiment, New Zealand white male rabbits were exposed to low and high doses of CY, PBO, and their combinations, for 4 months. Genotoxicity and cytotoxicity were monitored by measuring binucleated cells with micronuclei (BNMN), micronuclei (MN) and the cytokinesis block proliferation index (CBPI) in lymphocytes. After two months of exposure, a statistically significant increase in the frequency of BNMN was observed for all exposed animals (p < 0.001) in a dose-dependent way. MN were significantly elevated compared to controls (p < 0.001), with high dose groups reaching a 442% increase when co-exposed. BNMN and MN continued to increase after four months. Histopathological examination of lesions showed damage involving inflammation, attaining lymphoplasmatocytic infiltration in the high dose groups. Both CY and PBO cause liver and kidney inflammation and induce genotoxicity. PMID:27321377

  13. Contribution of nitric oxide to exercise-induced changes in healthy volunteers: effects of acute exercise and long-term physical training.

    Science.gov (United States)

    Poveda, J J; Riestra, A; Salas, E; Cagigas, M L; López-Somoza, C; Amado, J A; Berrazueta, J R

    1997-11-01

    Endothelium plays a central role in the regulation of regional blood flow through the release of certain vasoactive substances. We conducted this study to test whether an increase in the production of nitric oxide (NO) metabolites, atrial natriuretic peptide (ANP) and plasma and intraplatelet cyclic guanosine 3':5' monophosphate (cGMP) is involved in the adaptation to chronic exercise in physically trained people and in the vasodilatation induced by acute physical exercise. We studied one group of 10 trained athletes and another group of 10 untrained people. We measured plasma levels of nitrites, nitrates and cGMP and intraplatelet levels of cGMP, as an indicator of intracellular guanylate cyclase activity, and ANP before and after a maximal treadmill test. Resting cardiac rate (CR) and systolic blood pressure (SBP) were lower in the athlete group than in the control group (73.8 +/- 3.6 vs. 92 +/- 5.9; P plasma nitrites were 4.9 +/- 0.8 in the athlete group and 1.9 +/- 0.3 in the control group (P changes. Plasma levels of cGMP and ANP increased in both groups after the treadmill test, with no differences between groups. Among the athletes, cGMP increased from 1.11 +/- 0.1 to 2.6 +/- 0.4 (P plasma cGMP rose from 1.14 +/- 0.09 to 1.86 +/- 0.2 (P plasma cGMP and the atrial natriuretic peptide in both groups (r = 0.91, P concentration of cGMP did not show differences between groups and did not change after exercise. In conclusion, we have found increased basal levels of plasma nitrite and nitrate in trained subjects. Exercise does not produce differences in the increments of these metabolites. Therefore, we speculate the release of nitric oxide is not augmented by exercise in trained athletes. PMID:9395795

  14. Methamphetamine-induced short-term increase and long-term decrease in spatial working memory affects protein Kinase M zeta (PKMζ), dopamine, and glutamate receptors.

    Science.gov (United States)

    Braren, Stephen H; Drapala, Damian; Tulloch, Ingrid K; Serrano, Peter A

    2014-01-01

    Methamphetamine (MA) is a toxic, addictive drug shown to modulate learning and memory, yet the neural mechanisms are not fully understood. We investigated the effects of 2 weekly injections of MA (30 mg/kg) on working memory using the radial 8-arm maze (RAM) across 5 weeks in adolescent-age mice. MA-treated mice show a significant improvement in working memory performance 1 week following the first MA injection compared to saline-injected controls. Following 5 weeks of MA abstinence mice were re-trained on a reference and working memory version of the RAM to assess cognitive flexibility. MA-treated mice show significantly more working memory errors without effects on reference memory performance. The hippocampus and dorsal striatum were assessed for expression of glutamate receptors subunits, GluA2 and GluN2B; dopamine markers, dopamine 1 receptor (D1), dopamine transporter (DAT) and tyrosine hydroxylase (TH); and memory markers, protein kinase M zeta (PKMζ) and protein kinase C zeta (PKCζ). Within the hippocampus, PKMζ and GluA2 are both significantly reduced after MA supporting the poor memory performance. Additionally, a significant increase in GluN2B and decrease in D1 identifies dysregulated synaptic function. In the striatum, MA treatment increased cytosolic DAT and TH levels associated with dopamine hyperfunction. MA treatment significantly reduced GluN2B while increasing both PKMζ and PKCζ within the striatum. We discuss the potential role of PKMζ/PKCζ in modulating dopamine and glutamate receptors after MA treatment. These results identify potential underlying mechanisms for working memory deficits induced by MA. PMID:25566006

  15. Methamphetamine-induced short-term increase and long-term decrease in spatial working memory affects Protein Kinase M zeta (PKMζ, dopamine, and glutamate receptors

    Directory of Open Access Journals (Sweden)

    Stephen H Braren

    2014-12-01

    Full Text Available Methamphetamine (MA is a toxic, addictive drug shown to modulate learning and memory, yet the neural mechanisms are not fully understood. We investigated the effects of 2 weekly injections of MA (30 mg/kg on working memory using the radial 8-arm maze (RAM across 5 weeks in adolescent-age mice. MA-treated mice show a significant improvement in working memory performance 1 week following the first MA injection compared to saline-injected controls. Following 5 weeks of MA abstinence mice were re-trained on a reference and working memory version of the RAM to assess cognitive flexibility. MA-treated mice show significantly more working memory errors without effects on reference memory performance. The hippocampus and dorsal striatum were assessed for expression of glutamate receptors subunits, GluA2 and GluN2B; dopamine markers, dopamine 1 receptor (D1, dopamine transporter (DAT and tyrosine hydroxylase (TH; and memory markers, protein kinase M zeta (PKMζ and protein kinase C zeta (PKCζ. Within the hippocampus, PKMζ and GluA2 are both significantly reduced after MA supporting the poor memory performance. Additionally, a significant increase in GluN2B and decrease in D1 identifies dysregulated synaptic function. In the striatum, MA treatment increased cytosolic DAT and TH levels associated with dopamine hyperfunction. MA treatment significantly reduced GluN2B while increasing both PKMζ and PKCζ within the striatum. We discuss the potential role of PKMζ/PKCζ in modulating dopamine and glutamate receptors after MA treatment. These results identify potential underlying mechanisms for working memory deficits induced by MA.

  16. Blockade of lysophosphatidic acid receptors LPAR1/3 ameliorates lung fibrosis induced by irradiation

    International Nuclear Information System (INIS)

    Highlights: → Lysophosphatidic acid (LPA) levels and its receptors LPAR1/3 transcripts were elevated during the development of radiation-induced lung fibrosis. → Lung fibrosis was obviously alleviated in mice treated with the dual LPAR1/3 antagonist, VPC12249. → VPC12249 administration effectively inhibited radiation-induced fibroblast accumulation in vivo, and suppressed LPA-induced fibroblast proliferation in vitro. → LPA-LPAR1/3 signaling regulated TGFβ1 and CTGF expressions in radiation-challenged lungs, but only influenced CTGF expression in cultured fibroblasts. → LPA-LPAR1/3 signaling induced fibroblast proliferation through a CTGF-dependent pathway, rather than through TGFβ1 activation. -- Abstract: Lung fibrosis is a common and serious complication of radiation therapy for lung cancer, for which there are no efficient treatments. Emerging evidence indicates that lysophosphatidic acid (LPA) and its receptors (LPARs) are involved in the pathogenesis of fibrosis. Here, we reported that thoracic radiation with 16 Gy in mice induced development of radiation lung fibrosis (RLF) accompanied by obvious increases in LPA release and LPAR1 and LPAR3 (LPAR1/3) transcripts. RLF was significantly alleviated in mice treated with the dual LPAR1/3 antagonist, VPC12249. VPC12249 administration effectively prolonged animal survival, restored lung structure, inhibited fibroblast accumulation and reduced collagen deposition. Moreover, profibrotic cytokines in radiation-challenged lungs obviously decreased following administration of VPC12249, including transforming growth factor β1 (TGFβ1) and connective tissue growth factor (CTGF). In vitro, LPA induced both fibroblast proliferation and CTGF expression in a dose-dependent manner, and both were suppressed by blockade of LPAR1/3. The pro-proliferative activity of LPA on fibroblasts was inhibited by siRNA directed against CTGF. Together, our data suggest that the LPA-LPAR1/3 signaling system is involved in the

  17. Blockade of lysophosphatidic acid receptors LPAR1/3 ameliorates lung fibrosis induced by irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Gan, Lu [State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu (China); Xue, Jian-Xin [Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu (China); Laboratory of Stem Cell Biology, West China Hospital, Sichuan University, Chengdu (China); Li, Xin [Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu (China); Liu, De-Song [Department of Pediatrics, Sichuan Provincial Hospital of Women and Children, Chengdu (China); Ge, Yan; Ni, Pei-Yan; Deng, Lin [State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu (China); Lu, You, E-mail: radyoulu@hotmail.com [State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu (China); Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu (China); Jiang, Wei, E-mail: wcumsjw72@hotmail.com [State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu (China); Molecular Medicine Research Center, West China Hospital, Sichuan University, Chengdu (China)

    2011-05-27

    Highlights: {yields} Lysophosphatidic acid (LPA) levels and its receptors LPAR1/3 transcripts were elevated during the development of radiation-induced lung fibrosis. {yields} Lung fibrosis was obviously alleviated in mice treated with the dual LPAR1/3 antagonist, VPC12249. {yields} VPC12249 administration effectively inhibited radiation-induced fibroblast accumulation in vivo, and suppressed LPA-induced fibroblast proliferation in vitro. {yields} LPA-LPAR1/3 signaling regulated TGF{beta}1 and CTGF expressions in radiation-challenged lungs, but only influenced CTGF expression in cultured fibroblasts. {yields} LPA-LPAR1/3 signaling induced fibroblast proliferation through a CTGF-dependent pathway, rather than through TGF{beta}1 activation. -- Abstract: Lung fibrosis is a common and serious complication of radiation therapy for lung cancer, for which there are no efficient treatments. Emerging evidence indicates that lysophosphatidic acid (LPA) and its receptors (LPARs) are involved in the pathogenesis of fibrosis. Here, we reported that thoracic radiation with 16 Gy in mice induced development of radiation lung fibrosis (RLF) accompanied by obvious increases in LPA release and LPAR1 and LPAR3 (LPAR1/3) transcripts. RLF was significantly alleviated in mice treated with the dual LPAR1/3 antagonist, VPC12249. VPC12249 administration effectively prolonged animal survival, restored lung structure, inhibited fibroblast accumulation and reduced collagen deposition. Moreover, profibrotic cytokines in radiation-challenged lungs obviously decreased following administration of VPC12249, including transforming growth factor {beta}1 (TGF{beta}1) and connective tissue growth factor (CTGF). In vitro, LPA induced both fibroblast proliferation and CTGF expression in a dose-dependent manner, and both were suppressed by blockade of LPAR1/3. The pro-proliferative activity of LPA on fibroblasts was inhibited by siRNA directed against CTGF. Together, our data suggest that the LPA-LPAR1

  18. Health policy model: long-term predictive results associated with the management of hepatitis C virus-induced diseases in Italy

    Science.gov (United States)

    Mennini, Francesco Saverio; Marcellusi, Andrea; Andreoni, Massimo; Gasbarrini, Antonio; Salomone, Salvatore; Craxì, Antonio

    2014-01-01

    ,800 subjects were actually being treated with anti-HCV drugs. A reduction of health care costs is associated with a prevalence decrease. Indeed, once the spending peak is reached during this decade (about €527 million), the model predicts a cost reduction in the following 18 years. In 2030, based on the more effective treatments currently available, the direct health care cost associated with the management of HCV patients may reach €346 million (−34.3% compared to 2012). The first scenario (new treatment in 2015 with SVR =90% and same number of treated patients) was associated with a significant reduction in HCV-induced clinical consequences (prevalence =−3%) and a decrease in direct health care expenses, corresponding to €11.1 million. The second scenario (increase in treated patients to 12,790) produced an incremental cost reduction of €7.3 million, reaching a net decrease equal to €18.4 million. In the third scenario (treated patients =16,770), a higher net direct health care cost decrease versus the base-case (€44.0 million) was estimated. Conclusion Our model showed that the introduction of new treatments that are more effective could result in a quasi-eradication of HCV, with a very strong reduction in prevalence. PMID:24971024

  19. Health policy model: long-term predictive results associated with the management of hepatitis C virus-induced diseases in Italy

    Directory of Open Access Journals (Sweden)

    Mennini FS

    2014-06-01

    randomized clinical trial (RCT relating to boceprevir and telaprevir. For genotypes 2/3 patients it was assumed that treatment efficacy with dual therapy was equal to a SVR rate from the literature. According to the aim of this study, only direct health care costs (hospital admissions, drugs, treatment, and care of patients incurred by the Italian NHS have been included in the model. Costs have been extrapolated using the published scientific literature available in Italy and actualized with the 2012 ISTAT (Istituto Nazionale di Statistica Price Index system for monetary revaluation. Three different scenarios were assumed in order to evaluate the impact of future anti-HCV treatments on the burden of disease.Results: Overall, in Italy, 1.2 million infected subjects were estimated in 2012. Of these, about 211,000 patients were diagnosed, while only about 11,800 subjects were actually being treated with anti-HCV drugs. A reduction of health care costs is associated with a prevalence decrease. Indeed, once the spending peak is reached during this decade (about €527 million, the model predicts a cost reduction in the following 18 years. In 2030, based on the more effective treatments currently available, the direct health care cost associated with the management of HCV patients may reach €346 million (−34.3% compared to 2012. The first scenario (new treatment in 2015 with SVR =90% and same number of treated patients was associated with a significant reduction in HCV-induced clinical consequences (prevalence =−3% and a decrease in direct health care expenses, corresponding to €11.1 million. The second scenario (increase in treated patients to 12,790 produced an incremental cost reduction of €7.3 million, reaching a net decrease equal to €18.4 million. In the third scenario (treated patients =16,770, a higher net direct health care cost decrease versus the base-case (€44.0 million was estimated.Conclusion: Our model showed that the introduction of new treatments

  20. Long Term Preservation of Digital Information.

    Science.gov (United States)

    Lorie, Raymond A.

    The preservation of digital data for the long term presents a variety of challenges from technical to social and organizational. The technical challenge is to ensure that the information, generated today, can survive long term changes in storage media, devices, and data formats. This paper presents a novel approach to the problem. It distinguishes…

  1. Quantum Interference Induced Photon Blockade in a Coupled Single Quantum Dot-Cavity System

    CERN Document Server

    Tang, Jing; Xu, Xiulai

    2015-01-01

    We propose an experimental scheme to implement a strong photon blockade with a single quantum dot coupled to a nanocavity. The photon blockade effect can be tremendously enhanced by driving the cavity and the quantum dot simultaneously with two classical laser fields. This enhancement of photon blockade is ascribed to the quantum interference effect to avoid two-photon excitation of the cavity field. Comparing with Jaynes-Cummings model, the second-order correlation function at zero time delay $g^{(2)}(0)$ in our scheme can be reduced by two orders of magnitude and the system sustains a large intracavity photon number. A red (blue) cavity-light detuning asymmetry for photon quantum statistics with bunching or antibunching characteristics is also observed. The photon blockade effect has a controllable flexibility by tuning the relative phase between the two pumping laser fields and the Rabi coupling strength between the quantum dot and the pumping field. Moreover, the photon blockade scheme based on quantum in...

  2. Landslides induced by heavy rainfall in July 2012 in Northern Kyushu District, Japan and the influence of long term rainfall increase comparing with the slope destabilization due to strong seismic shaking

    Science.gov (United States)

    Kubota, Tetsuya; Shinohara, Yoshinori; Aditian, Aril

    2013-04-01

    1. Objective We had a deluge in July 2012 in the northern Kyushu district with intense rainfall of 800mm and 108mm/hr. This intensity yielded countless traces of debris flow and landslides, slope failures that induced tremendous damage and causalities in the area. Hence, several field investigations and reconnaissance tasks were conducted to delve into this sediment-related disaster. The various results and the information obtained through this investigation were reported, mentioning the damage, the meteorological condition, geologic-geomorphologic features and hydraulic characteristics of the debris flows, vegetation effects, and the influence of the climate change. Increase in rainfall that may be induced by the global climate change is obvious in Kyushu district, Japan, according to the analysis of rain data observed in various locations including mountainside points that are not influenced by local warming due to urbanization. On this point of view, we are intrigued to elucidate the response of landslide to this increase in rainfall. Hence, its long term impact on this landslide disaster is also analyzed comparing with the slope destabilization due to strong seismic shaking. 2. Method and target areas Field investigation on landslides slopes, slope failures and torrents where debris flows occurred are conducted to obtain the geologic data, geo-structure, vegetation feature, soil samples and topographic data i.e. cross sections, then soil shear tests and soil permeability tests are also conducted. The rainfall data at the nearest rain observatory were obtained from the database of Japan meteorological agency. The long term impact on the slope stability at some slopes in the area is analyzed by the finite element method (FEM) combined with rain infiltration and seepage analysis with the long term rainfall fluctuation data, obtaining factor of safety ( Fs) on real landslide slopes. The results are compared with the destabilized influence on the slopes due to the

  3. Financing Purchase of long-term Property

    OpenAIRE

    Pastyřík, Jaroslav

    2012-01-01

    Bachelor’s thesis is focused on issues of financing a purchase of long-term property in specific company. Particular variations of purchase and financing of fixed assets are described in the teoretical part of the thesis, presentation of the specific company and long-term property that is purchased and variations of financing are described in the practical part of the thesis. The aim of the thesis is to assess possible recources of financing purchase of long-term property in the specific comp...

  4. Long term prediction of flood occurrence

    Science.gov (United States)

    Aguilar, Cristina; Montanari, Alberto; José Polo, María

    2016-05-01

    How long a river remembers its past is still an open question. Perturbations occurring in large catchments may impact the flow regime for several weeks and months, therefore providing a physical explanation for the occasional tendency of floods to occur in clusters. The research question explored in this paper may be stated as follows: can higher than usual river discharges in the low flow season be associated to a higher probability of floods in the subsequent high flow season? The physical explanation for such association may be related to the presence of higher soil moisture storage at the beginning of the high flow season, which may induce lower infiltration rates and therefore higher river runoff. Another possible explanation is persistence of climate, due to presence of long-term properties in atmospheric circulation. We focus on the Po River at Pontelagoscuro, whose catchment area amounts to 71 000 km2. We look at the stochastic connection between average river flows in the pre-flood season and the peak flows in the flood season by using a bivariate probability distribution. We found that the shape of the flood frequency distribution is significantly impacted by the river flow regime in the low flow season. The proposed technique, which can be classified as a data assimilation approach, may allow one to reduce the uncertainty associated to the estimation of the flood probability.

  5. Long term wet spent nuclear fuel storage

    International Nuclear Information System (INIS)

    The meeting showed that there is continuing confidence in the use of wet storage for spent nuclear fuel and that long-term wet storage of fuel clad in zirconium alloys can be readily achieved. The importance of maintaining good water chemistry has been identified. The long-term wet storage behaviour of sensitized stainless steel clad fuel involves, as yet, some uncertainties. However, great reliance will be placed on long-term wet storage of spent fuel into the future. The following topics were treated to some extent: Oxidation of the external surface of fuel clad, rod consolidation, radiation protection, optimum methods of treating spent fuel storage water, physical radiation effects, and the behaviour of spent fuel assemblies of long-term wet storage conditions. A number of papers on national experience are included

  6. Long-Term Care Ombudsman Program

    Science.gov (United States)

    ... Strategic Plan Federal Initiatives Career Opportunities Contact Us Administration on Aging (AoA) Long-Term Care Ombudsman Program ( ... Section Q Fact Sheet Back to top Funding History Older Americans Act Title VII Chapter 2 (Ombudsman ...

  7. Long-Term Ownership by Industrial Foundations

    DEFF Research Database (Denmark)

    Børsting, Christa Winther; Kuhn, Johan Moritz; Poulsen, Thomas;

    2016-01-01

    Short-termism has become a serious concern for businesses and policy makers and this has inspired a search for governance arrangement to promote long term decision making. In this paper we study a particularly long-term ownership structure, which is fairly common in Northern Europe, particularly in...... Denmark. Industrial foundations are independent legal entities without owners or members typically with the dual objective of preserving the company and using excess profits for charity. We use a unique Danish data set to examine the governance of foundation-owned companies. We show that they are long......-term in several respects. Foundations hold on to their shares for longer. Foundation-owned companies replace managers less frequently. They have more conservative capital structures with less leverage. Their companies survive longer. Their business decisions appear to be more long term. This paper...

  8. Long-term outcome of meniscectomy

    DEFF Research Database (Denmark)

    Roos, Ewa M.; Ostenberg, A; Roos, H; Ekdahl, C; Lohmander, L S

    2001-01-01

    To describe the long-term influence of meniscectomy on pain, functional limitations, and muscular performance. To assess the effects of radiographic osteoarthritis (OA), gender and age on these outcomes in patients with meniscectomy....

  9. Long Term Care Minimum Data Set (MDS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Long-Term Care Minimum Data Set (MDS) is a standardized, primary screening and assessment tool of health status that forms the foundation of the comprehensive...

  10. Glucose intolerance induced by blockade of central FGF receptors is linked to an acute stress response

    Directory of Open Access Journals (Sweden)

    Jennifer M. Rojas

    2015-08-01

    Conclusions: The effect of acute inhibition of central FGFR signaling to impair glucose tolerance likely involves a stress response associated with pronounced, but transient, sympathoadrenal activation and an associated reduction of insulin secretion. Whether this effect is a true consequence of FGFR blockade or involves an off-target effect of the FGFR inhibitor requires additional study.

  11. Wastewater treatment by soil infiltration: Long-term phosphorus removal

    Science.gov (United States)

    Eveborn, David; Kong, Deguo; Gustafsson, Jon Petter

    2012-10-01

    Phosphorus (P) leaching from on-site wastewater treatment systems may contribute to eutrophication. In developed countries the most common on-site treatment technique is septic systems with soil infiltration. However, the current knowledge about long term P removal in soil treatment systems is not well developed and the data used for estimation of P losses from such systems are unreliable. In this study we sampled four filter beds from community-scale soil treatment systems with an age of between 14 and 22 years to determine the long-term P removal and to investigate the chemical mechanisms behind the observed removal. For one site the long-term P removal was calculated using a mass balance approach. After analysis of the accumulated P, it was estimated that on average 12% of the long-term P load had been removed by the bed material. This indicates a low overall capacity of soil treatment systems to remove phosphorus. Batch experiments and chemical speciation modelling indicated that calcium phosphate precipitation was not an important long-term P removal mechanism, with the possible exception of one of the sites. More likely, the P removal was induced by AlPO4 precipitation and/or sorption to poorly ordered aluminium compounds, as evidenced by strong relationships between oxalate-extractable Al and P.

  12. Long-term Treatment in Bipolar Disorder

    OpenAIRE

    Meliha Zengin Eroglu; Nurgul Ozpoyraz

    2010-01-01

    Although the importance of long-term prophylactic treatment is certain in bipolar disorder, there is stil debate on how to which patients and evaluate the treatment response. Efficacious long-term treatment can reduce morbidity and mortality significantly and improve quality of life of bipolar patients. The concept of ideal response should also be defined very clearly in order to discuss the difficulties of measuring the effectiveness of the prophylactic treatment. The aims of this paper are ...

  13. Long-term e-arhiv

    OpenAIRE

    Petkovšek , Bojan

    2011-01-01

    With expansion of e-business and consequently with creating original electronic documents, legally compliant long-term digital preservation has become a commitment for organizations that do business electronically. Accepted legislation that equalizes the legal validity of electronic documents with their paper original, regulates the operating and preservation of documents, recommendations, existing standards and service and equipment providers for ensuring long-term digital preservation, enab...

  14. Databases Strengthen Long-Term Care Partnerships

    OpenAIRE

    Ann D Bagchi Jung Y Kim

    2008-01-01

    The Community Partnerships for Older Adults program provided grants to eight community partnerships to develop and implement creative strategies for improving awareness about long-term care and supportive services systems. This brief examines three partnerships—Aging Atlanta, El Paso Successful Aging Through Long-Term Strategic Alliances, and the San Francisco Partnership for Community-Based Care and Support—with different levels of information technology expertise that designed databases...

  15. Databases Strengthen Long-Term Care Partnerships.

    OpenAIRE

    Ann Bagchi; Jung Kim

    2008-01-01

    The Community Partnerships for Older Adults program provided grants to eight community partnerships to develop and implement creative strategies for improving awareness about long-term care and supportive services systems. This brief examines three partnerships—Aging Atlanta, El Paso Successful Aging Through Long-Term Strategic Alliances, and the San Francisco Partnership for Community-Based Care and Support—with different levels of information technology expertise that designed databases...

  16. Manganese in long term paediatric parenteral nutrition.

    OpenAIRE

    Reynolds, A. P.; Kiely, E; Meadows, N

    1994-01-01

    The current practice of providing manganese supplementation to neonates on long term parenteral nutrition is leading to a high incidence of hypermanganesaemia. Magnetic resonance imaging (MRI) studies in adults on long term manganese parenteral nutrition have shown changes in TI weighted MRI images and similar findings in a neonate receiving trace element supplementation are reported here. Whole blood manganese concentration in the infant was 1740 nmol/l (or 8.3 times upper reference limit). ...

  17. Homologue of Protein Kinase Mζ Maintains Context Aversive Memory and Underlying Long-Term Facilitation in Terrestrial Snail Helix.

    Directory of Open Access Journals (Sweden)

    Pavel M. Balaban

    2015-06-01

    Full Text Available It has been shown that a variety of long-term memories in different regions of the brain and in different species are quickly erased by local inhibition of PKMζ. Using antibodies to mammalian PKMζ, we describe in the present study the localization of immunoreactive molecules in the nervous system of the terrestrial snail Helix lucorum. Presence of a homologue of PKMζ was confirmed with transcriptomics. We have demonstrated in behavioral experiments that contextual fear memory disappeared under a blockade of PKMζ with a selective peptide blocker of PKMζ (ZIP, but not with scrambled ZIP. If ZIP was combined with a reminder (20 min in noxious context, no impairment of the long-term contextual memory was observed. In electrophysiological experiments we investigated whether PKMζ takes part in the maintenance of long-term facilitation (LTF in the neural circuit mediating tentacle withdrawal. LTF of excitatory synaptic inputs to premotor interneurons was induced by high-frequency nerve stimulation combined with serotonin bath applications and lasted at least four hours. We found that bath application of 2x10-6 M ZIP at the 90th min after the tetanization reduced the EPSP amplitude to the non-tetanized EPSP values. Applications of the scrambled ZIP peptide at a similar time and concentration didn't affect the EPSP amplitudes. In order to test whether effects of ZIP are specific to the synapses, we performed experiments with LTF of somatic membrane responses to local glutamate applications. It was shown earlier that serotonin application in such an artificial synapse condition elicits LTF of responses to glutamate. It was found that ZIP had no effect on LTF in these conditions, which may be explained by the very low concentration of PKMζ molecules in somata of these identified neurons, as evidenced by immunochemistry. Obtained results suggest that the Helix homologue of PKMζ might be involved in post-induction maintenance of long-term changes in

  18. Hyperfine-induced hysteretic funnel structure in spin blockaded tunneling current of coupled vertical quantum dots at low magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Leary, A.; Wicha, A.; Harack, B.; Coish, W. A.; Hilke, M. [Department of Physics, McGill University, Ernest Rutherford Building, 3600 rue University, Montreal, Quebec H3A 2T8 (Canada); Yu, G.; Gupta, J. A. [National Research Council of Canada, M50, Montreal Road, Ottawa, Ontario K1A 0R6 (Canada); Payette, C.; Austing, D. G. [Department of Physics, McGill University, Ernest Rutherford Building, 3600 rue University, Montreal, Quebec H3A 2T8, Canada and National Research Council of Canada, M50, Montreal Road, Ottawa, Ontario K1A 0R6 (Canada)

    2013-12-04

    We outline the properties of the hyperfine-induced funnel structure observed in the two-electron spin blockade region of a weakly coupled vertical double quantum dot device. Hysteretic steps in the leakage current occur due to dynamic nuclear polarization when either the bias voltage or the magnetic field is swept up and down. When the bias voltage is swept, an intriguing ∼3 mT wide cusp near 0 T appears in the down-sweep position, and when the magnetic field is swept, the current at 0 T can be switched from 'low' to 'high' as the bias is increased.

  19. Blockade of Wnt/β-Catenin Pathway Aggravated Silica-Induced Lung Inflammation through Tregs Regulation on Th Immune Responses

    Directory of Open Access Journals (Sweden)

    Wujing Dai

    2016-01-01

    Full Text Available CD4+ T cells play an important role in regulating silica-induced inflammation and fibrosis. Recent studies showed that Wnt/β-catenin pathway could modulate the function and the differentiation of CD4+ T cells. Therefore, Wnt/β-catenin pathway may participate in the development and progress of silicosis. To investigate the role of Wnt/β-catenin pathway, we used lentivirus expressing β-catenin shRNA to block the Wnt/β-catenin pathway by intratracheal instillation to the mice model of silicosis. Treatment of lentivirus could significantly aggravate the silica-induced lung inflammation and attenuated the fibrosis at the late stage. By analyzing CD4+ T cells, we found that blockade of Wnt/β-catenin pathway suppressed regulatory T cells (Tregs. Reciprocally, enhanced Th17 response was responsible for the further accumulation of neutrophils and production of proinflammatory cytokines. In addition, blockade of Wnt/β-catenin pathway delayed the Th1/Th2 polarization by inhibiting Tregs and Th2 response. These results indicated that Wnt/β-catenin pathway could regulate Tregs to modulate Th immune response, which finally altered the pathological character of silicosis. Our study suggested that Wnt/β-catenin pathway might be a potential target to treat the silica-induced inflammation and fibrosis.

  20. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis

    OpenAIRE

    Dubin, Krista; Callahan, Margaret K.; Ren, Boyu; Khanin, Raya; Viale, Agnes; Ling, Lilan; No, Daniel; Gobourne, Asia; Littmann, Eric; Huttenhower, Curtis; Pamer, Eric G.; Wolchok, Jedd D.

    2016-01-01

    The composition of the intestinal microbiota influences the development of inflammatory disorders. However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota's composition. Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune-med...

  1. Long-term follow-up study and long-term care of childhood cancer survivors

    Directory of Open Access Journals (Sweden)

    Hyeon Jin Park

    2010-04-01

    Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

  2. Long-term alteration of cementitious materials

    International Nuclear Information System (INIS)

    Long-term alteration of cementitious materials in the geological condition has been discussed for the safety assessment of radioactive waste disposal. This paper describes the status of understanding long-term chemical alteration of cement, by reviewing some of our investigations on this issue in which we developed a thermodynamic incongruent C-S-H dissolution/precipitation model and a reactive transport calculation code. Alteration of C-S-H gel in a saline groundwater and the change of chemical barrier performance of cementitious materials due to the alteration are also discussed. Some key issues to be discussed further are given and suggested for the future studies on the long-term alteration of cementitious materials in the repository environment. (author)

  3. Quality measures of imaging mass spectrometry aids in revealing long-term striatal protein changes induced by neonatal exposure to the cyanobacterial toxin β-N-methylamino-L-alanine (BMAA).

    Science.gov (United States)

    Karlsson, Oskar; Bergquist, Jonas; Andersson, Malin

    2014-01-01

    and myelination, which might be important for the previously shown BMAA-induced long-term cognitive impairments. PMID:24126143

  4. Quality Measures of Imaging Mass Spectrometry Aids in Revealing Long-term Striatal Protein Changes Induced by Neonatal Exposure to the Cyanobacterial Toxin β-N-methylamino-L-alanine (BMAA)*

    Science.gov (United States)

    Karlsson, Oskar; Bergquist, Jonas; Andersson, Malin

    2014-01-01

    and myelination, which might be important for the previously shown BMAA-induced long-term cognitive impairments. PMID:24126143

  5. Prior DNA immunization enhances immune response to dominant and subdominant viral epitopes induced by a fowlpox-based SIVmac vaccine in long-term slow-progressor macaques infected with SIVmac251

    International Nuclear Information System (INIS)

    A therapeutic vaccine for individuals infected with HIV-1 and treated with antiretroviral therapy (ART) should be able to replenish virus-specific CD4+ T-cells and broaden the virus-specific CD8+ T-cell response in order to maintain CD8+ T-cell function and minimize viral immune escape after ART cessation. Because a combination of DNA and recombinant poxvirus vaccine modalities induces high levels of virus-specific CD4+ T-cell response and broadens the cytolytic activity in naive macaques, we investigated whether the same results could be obtained in SIVmac251-infected macaques. The macaques studied here were long-term nonprogressors that naturally contained viremia but were nevertheless treated with a combination of antiviral drugs to assess more carefully the effect of vaccination in the context of ART. The combination of a DNA expressing the gag and pol genes (DNA-SIV-gp) of SIVmac239 followed by a recombinant fowlpox expressing the same SIVmac genes (FP-SIV-gp) was significantly more immunogenic than two immunizations of FP-SIV-gp in SIVmac251-infected macaques treated with ART. The DNA/FP combination significantly expanded and broadened Gag-specific T-cell responses measured by tetramer staining, ELISPOT, and intracellular cytokine staining and measurement of ex vivo cytolytic function. Importantly, the combination of these vaccine modalities also induced a sizeable expansion in most macaques of Gag-specific CD8-(CD4+) T-cells able to produce TNF-α. Hopefully, this modality of vaccine combination may be useful in the clinical management of HIV-1-infected individuals

  6. A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia

    DEFF Research Database (Denmark)

    Duvaldestin, Philippe; Kuizenga, Karel; Saldien, Vera;

    2010-01-01

    Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular...... blockade in patients induced and maintained under propofol anesthesia. However, sevoflurane anesthesia, unlike propofol, can prolong the effect of neuromuscular blocking drugs (NMBDs) such as rocuronium and vecuronium.......Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular...

  7. Long-term home care scheduling

    DEFF Research Database (Denmark)

    Gamst, Mette; Jensen, Thomas Sejr

    In several countries, home care is provided for certain citizens living at home. The long-term home care scheduling problem is to generate work plans spanning several days such that a high quality of service is maintained and the overall cost is kept as low as possible. A solution to the problem...... provides detailed information on visits and visit times for each employee on each of the covered days. We propose a branch-and-price algorithm for the long-term home care scheduling problem. The pricing problem generates one-day plans for an employee, and the master problem merges the plans with respect...

  8. Long-term effects of forced migration

    OpenAIRE

    Markus Jäntti; Matti Sarvimäki; Roope Uusitalo

    2009-01-01

    We study the long-term effects of human displacement using individual level panel data on forced migrants and comparable non-migrants. After World War II, Finland ceded a tenth of its territory to the Soviet Union and resettled the entire population living in these areas in the remaining parts of the country. We find that displacement increased the long-term income of men, but had no effect on that of women. We attribute a large part of the effect to faster transition from traditional (rural)...

  9. Long-Term Effects of Forced Migration

    OpenAIRE

    Sarvimäki, Matti; Uusitalo, Roope; Jäntti, Markus

    2009-01-01

    We study the long-term effects of human displacement using individual-level panel data on forced migrants and comparable non-migrants. After World War II, Finland ceded a tenth of its territory to the Soviet Union and resettled the entire population living in these areas in the remaining parts of the country. We find that displacement increased the long-term income of men, but had no effect on that of women. We attribute a large part of the effect to faster transition from traditional (rural)...

  10. Long-term effects of forced migration

    OpenAIRE

    Sarvimäki, Matti; Uusitalo, Roope; Jäntti, Markus

    2009-01-01

    We study the long-term effects of human displacement using individual-level panel data on forced migrants and comparable non-migrants. After World War II, Finland ceded a tenth of its territory to the Soviet Union and resettled the entire population living in these areas in the remaining parts of the country. We find that displacement increased the long-term income of men, but had no effect on that of women. We attribute a large part of the effect to faster transition from traditional (rural)...

  11. Perioperative Nerve Blockade: Clues from the Bench

    Directory of Open Access Journals (Sweden)

    M. R. Suter

    2011-01-01

    Full Text Available Peripheral and neuraxial nerve blockades are widely used in the perioperative period. Their values to diminish acute postoperative pain are established but other important outcomes such as chronic postoperative pain, or newly, cancer recurrence, or infections could also be influenced. The long-term effects of perioperative nerve blockade are still controversial. We will review current knowledge of the effects of blocking peripheral electrical activity in different animal models of pain. We will first go over the mechanisms of pain development and evaluate which types of fibers are activated after an injury. In the light of experimental results, we will propose some hypotheses explaining the mitigated results obtained in clinical studies on chronic postoperative pain. Finally, we will discuss three major disadvantages of the current blockade: the absence of blockade of myelinated fibers, the inappropriate duration of blockade, and the existence of activity-independent mechanisms.

  12. PSA modeling of long-term accident sequences

    International Nuclear Information System (INIS)

    In the traditional Level 1 PSA, the long term of the accident sequences is usually taken into account in a simplified manner. For example, some of the mitigations which are needed at long term are taken into account in the PSA, but the analysis and the associated failures probabilities quantification are estimated based on generic assessments. In the context of the extension of PSA scope to include the external hazards, in France, both operator (EDF) and IRSN work for the improvement of methods to better take into account in the PSA the long term of accident sequences induced by initiators which affect the whole site containing several nuclear installations (reactors, fuel pools, ...). This is an essential prerequisite for the development of external hazards PSA. It has to be noted that in the French PSA, even before Fukushima, this type of accident sequences was already taken into account, many insight being used, as complementary information, to enhance the safety level of the plants. The recent French and international operating experience is an opportunity for tuning the actual PSA methods for long term accident sequences modeling. The paper presents the main results of the ongoing efforts in this area. (author)

  13. Long-Term Outcome of Idiopathic Macrocephaly

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-11-01

    Full Text Available The neuroradiological, developmental, and psychological, long-term sequelae of 41 infants (30 boys, 11 girls diagnosed with macrocephaly (an occipito-facial head circumference [OFC] >95th centile at a family health service visit between 1985 and 1986 were studied at the Royal Alexandra Hospital for Children and other centers in Sydney, Australia.

  14. Long-Term Stability of Social Participation

    Science.gov (United States)

    Hyyppa, Markku T.; Maki, Juhani; Alanen, Erkki; Impivaara, Olli; Aromaa, Arpo

    2008-01-01

    The long-term stability of social participation was investigated in a representative urban population of 415 men and 579 women who had taken part in the nationwide Mini-Finland Health Survey in the years 1978-1980 and were re-examined 20 years later. Stability was assessed by means of the following tracking coefficients: kappa, proportion of…

  15. Long-term fixed income market structure

    Science.gov (United States)

    Grilli, Luca

    2004-02-01

    Long-term fixed income market securities present a strong positive correlation in daily returns. By using a metrical approach and considering “modified” time series, I show how it is possible to show a more complex structure which depends strictly on the maturity date.

  16. Long term prospects for double beta decay

    OpenAIRE

    Zuber, K.

    2010-01-01

    In rather general terms the long term perspective of double beta decay is discussed. All important experimental parameters are investigated as well as the status of nuclear matrix element issues. The link with other neutrino physics results and options to disentangle the underlying physics process are presented.

  17. Synaptic long-term potentiation and depression in the rat medial vestibular nuclei depend on neural activation of estrogenic and androgenic signals.

    Directory of Open Access Journals (Sweden)

    Mariangela Scarduzio

    Full Text Available Estrogenic and androgenic steroids can be synthesised in the brain and rapidly modulate synaptic transmission and plasticity through direct interaction with membrane receptors for estrogens (ERs and androgens (ARs. We used whole cell patch clamp recordings in brainstem slices of male rats to explore the influence of ER and AR activation and local synthesis of 17β-estradiol (E2 and 5α-dihydrotestosterone (DHT on the long-term synaptic changes induced in the neurons of the medial vestibular nucleus (MVN. Long-term depression (LTD and long-term potentiation (LTP caused by different patterns of high frequency stimulation (HFS of the primary vestibular afferents were assayed under the blockade of ARs and ERs or in the presence of inhibitors for enzymes synthesizing DHT (5α-reductase and E2 (P450-aromatase from testosterone (T. We found that LTD is mediated by interaction of locally produced androgens with ARs and LTP by interaction of locally synthesized E2 with ERs. In fact, the AR block with flutamide prevented LTD while did not affect LTP, and the blockade of ERs with ICI 182,780 abolished LTP without influencing LTD. Moreover, the block of P450-aromatase with letrozole not only prevented the LTP induction, but inverted LTP into LTD. This LTD is likely due to the local activation of androgens, since it was abolished under blockade of ARs. Conversely, LTD was still induced in the presence of finasteride the inhibitor of 5α-reductase demonstrating that T is able to activate ARs and induce LTD even when DHT is not synthesized. This study demonstrates a key and opposite role of sex neurosteroids in the long-term synaptic changes of the MVN with a specific role of T-DHT for LTD and of E2 for LTP. Moreover, it suggests that different stimulation patterns can lead to LTD or LTP by specifically activating the enzymes involved in the synthesis of androgenic or estrogenic neurosteroids.

  18. The Validity Chlorophyll-a Estimation by Sun Induced Fluorescence in Estuarine Waters: An Analysis of Long-term (2003-2011) Water Quality Data from Tampa Bay, Florida (USA)

    Science.gov (United States)

    Moreno-Madrinan, Max Jacobo; Fischer, Andrew

    2012-01-01

    Satellite observation of phytoplankton concentration or chlorophyll-a is an important characteristic, critically integral to monitoring coastal water quality. However, the optical properties of estuarine and coastal waters are highly variable and complex and pose a great challenge for accurate analysis. Constituents such as suspended solids and dissolved organic matter and the overlapping and uncorrelated absorptions in the blue region of the spectrum renders the blue-green ratio algorithms for estimating chlorophyll-a inaccurate. Measurement of sun-induced chlorophyll fluorescence, on the other hand, which utilizes the near infrared portion of the electromagnetic spectrum, may provide a better estimate of phytoplankton concentrations. While modelling and laboratory studies have illustrated both the utility and limitations of satellite baseline algorithms based on the sun induced chlorophyll fluorescence signal, few have examined the empirical validity of these algorithms using a comprehensive long term in situ data set. In an unprecedented analysis of a long term (2003-2011) in situ monitoring data from Tampa Bay, Florida (USA), we assess the validity of the FLH product from the Moderate Resolution Imaging Spectrometer (MODIS) against chlorophyll ]a and a suite of water quality parameters taken in a variety of conditions throughout a large optically complex estuarine system. A systematic analysis of sampling sites throughout the bay is undertaken to understand how the relationship between FLH and in situ chlorophyll-a responds to varying conditions within the estuary including water depth, distance from shore and structures and eight water quality parameters. From the 39 station for which data was derived, 22 stations showed significant correlations when the FLH product was matched with in situ chlorophyll-alpha data. The correlations (r2) for individual stations within Tampa Bay ranged between 0.67 (n=28, pless than 0.01) and-0.457 (n=12, p=.016), indicating that

  19. Long-Term Immunity to Lethal Acute or Chronic Type II Toxoplasma gondii Infection Is Effectively Induced in Genetically Susceptible C57BL/6 Mice by Immunization with an Attenuated Type I Vaccine Strain▿

    Science.gov (United States)

    Gigley, Jason P.; Fox, Barbara A.; Bzik, David J.

    2009-01-01

    C57BL/6 (B6) mice are genetically highly susceptible to chronic type II Toxoplasma gondii infections that invariably cause lethal toxoplasmic encephalitis. We examined the ability of an attenuated type I vaccine strain to elicit long-term immunity to lethal acute or chronic type II infections in susceptible B6 mice. Mice immunized with the type I cps1-1 vaccine strain were not susceptible to a lethal (100-cyst) challenge with the type II strain ME49. Immunized mice challenged with 10 ME49 cysts exhibited significant reductions in brain cyst and parasite burdens compared to naive mice, regardless of the route of challenge infection. Remarkably, cps1-1 strain-immunized B6 mice chronically infected with ME49 survived for at least 12 months without succumbing to the chronic infection. Potent immunity to type II challenge infections persisted for at least 10 months after vaccination. While the cps1-1 strain-elicited immunity did not prevent the establishment of a chronic infection or clear established brain cysts, cps1-1 strain-elicited CD8+ immune T cells significantly inhibited recrudescence of brain cysts during chronic ME49 infection. In addition, we show that uracil starvation of the cps1-1 strain induces early markers of bradyzoite differentiation. Collectively, these results suggest that more effective immune control of chronic type II infection in the genetically susceptible B6 background is established by vaccination with the nonreplicating type I uracil auxotroph cps1-1 strain. PMID:19797073

  20. Long-term immunity to lethal acute or chronic type II Toxoplasma gondii infection is effectively induced in genetically susceptible C57BL/6 mice by immunization with an attenuated type I vaccine strain.

    Science.gov (United States)

    Gigley, Jason P; Fox, Barbara A; Bzik, David J

    2009-12-01

    C57BL/6 (B6) mice are genetically highly susceptible to chronic type II Toxoplasma gondii infections that invariably cause lethal toxoplasmic encephalitis. We examined the ability of an attenuated type I vaccine strain to elicit long-term immunity to lethal acute or chronic type II infections in susceptible B6 mice. Mice immunized with the type I cps1-1 vaccine strain were not susceptible to a lethal (100-cyst) challenge with the type II strain ME49. Immunized mice challenged with 10 ME49 cysts exhibited significant reductions in brain cyst and parasite burdens compared to naive mice, regardless of the route of challenge infection. Remarkably, cps1-1 strain-immunized B6 mice chronically infected with ME49 survived for at least 12 months without succumbing to the chronic infection. Potent immunity to type II challenge infections persisted for at least 10 months after vaccination. While the cps1-1 strain-elicited immunity did not prevent the establishment of a chronic infection or clear established brain cysts, cps1-1 strain-elicited CD8(+) immune T cells significantly inhibited recrudescence of brain cysts during chronic ME49 infection. In addition, we show that uracil starvation of the cps1-1 strain induces early markers of bradyzoite differentiation. Collectively, these results suggest that more effective immune control of chronic type II infection in the genetically susceptible B6 background is established by vaccination with the nonreplicating type I uracil auxotroph cps1-1 strain. PMID:19797073

  1. A long-term multi-proxy record of varved sediments highlights climate-induced mixing-regime shift in a large hard-water lake ~5000 years ago

    Directory of Open Access Journals (Sweden)

    Walter Finsinger

    2014-06-01

    Full Text Available The long-term terrestrial and aquatic ecosystem dynamics spanning between approximately 6200 and 4800 cal BP were investigated using pollen, diatoms, pigments, charcoal, and geochemistry from varved sediments collected in a large stratified perialpine lake, Lago Grande di Avigliana, in the Italian Alps. Marked changes were detected in diatom and pigment assemblages and in sediment composition at ~4900 cal BP. Organic matter rapidly increased and diatom assemblages shifted from oligotrophic to oligo-mesotrophic planktonic assemblages suggesting that nutrients increased at that time. Because land cover, erosion, and fire frequency did not change significantly, external nutrient sources were possibly not essential in controlling the lake-ecosystem dynamics. This is also supported by redundancy analysis, which showed that variables explaining significant amounts of variance in the diatom data were not the ones related to changes in the catchment. Instead, the broad coincidence between the phytoplankton dynamics and rising lake-levels, cooler temperatures, and stronger spring winds in the northern Mediterranean borderlands possibly points to the effects of climate change on the nutrient recycling in the lake by means of the control that climate can exert on mixing depth. We hypothesize that the increased P-release rates and higher organic-matter accumulation rates, proceeded by enhanced precipitation of iron sulphides, were possibly caused by deeper and stronger mixing leading to enhanced input of nutrients from the anoxic hypolimnion into the epilimnion. Although we cannot completely rule out the influence of minor land-cover changes due to human activities, it may be hypothesized that climate-induced cumulative effects related to mixing regime and P-recycling from sediments influenced the aquatic-ecosystem dynamics.

  2. Humoral immune response induced by an engineered cell-based neuroblastoma vaccine with or without CD25 blockade

    Institute of Scientific and Technical Information of China (English)

    Jin Zheng; Rimas Orentas; Xiaofei Yan; Hongli Liu

    2011-01-01

    Neuroblastoma is the most common extracranial solid cancer in childhood and it can develop in the nerve tissue of the adrenal gland, neck, chest, or spinal cord A number of tumor-associated antigens(TAAs), which can elicit humoral immunity, have been identified in cancer patients. To investigate the humoral immunity during neuroblastoma development, we treated A/J mice with an aggressive clone of neuroblastoma(AGN2a)cells, then vaccinated the mice with cells expressing AGN2a-CD80/CD137L under the condihons with or without regulatory T cell blockade. Strong humoral immunity was induced by AGN2a-CD80/CD137L immunization in the context of regulatory T cell blockade. Sera from treated mice were used to screen an AGN2a cDNA expression library for identifying TAAs by SEREX(serological analysis of recombinant cDNA expression libraries). Clones were identified by sequencing and comparative analysis of gene pools. Further investigation of these gene products revealed that most of them play a role in the neuronal differentiation, cell metabolism, and are highly expressed in other types of malignancy. Asz1(ankyrin repeat, SAM, and basic leucine zipper domaincontaining protein)was found in all tumor-bearing groups. These results implicated that these candidates identified from tumor-bearing mice may be neuroblastoma-associated antigens, which can be used as biomarkers in early diagnosis of neuroblastoma, whereas those identified from vaccinated mice may be the potential therapeutic targets.

  3. Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial

    DEFF Research Database (Denmark)

    Pühringer, Friedrich K; Rex, Christopher; Sielenkämper, Andreas W;

    2008-01-01

    Sugammadex (Org 25969), a novel, selective relaxant binding agent, was specifically designed to rapidly reverse rocuronium-induced neuromuscular blockade. The efficacy and safety of sugammadex for the reversal of profound, high-dose rocuronium-induced neuromuscular blockade was evaluated....

  4. Notch signaling in Drosophila long-term memory formation

    OpenAIRE

    Ge, Xuecai; Hannan, Frances; Xie, Zuolei; Feng, Chunhua; Tully, Tim; Zhou, Haimeng; Xie, Zuoping; Zhong, Yi

    2004-01-01

    Notch (N) is a cell surface receptor that mediates an evolutionarily ancient signaling pathway to control an extraordinarily broad spectrum of cell fates and developmental processes. To gain insights into the functions of N signaling in the adult brain, we examined the involvement of N in Drosophila olfactory learning and memory. Long-term memory (LTM) was disrupted by blocking N signaling in conditional mutants or by acutely induced expression of a dominant-negative N transgene. In contrast,...

  5. Northern European long term climate archives

    Energy Technology Data Exchange (ETDEWEB)

    Hohl, Veronica [Stockholm Univ. (Sweden)

    2005-01-01

    The Swedish Nuclear Fuel and Waste Management Company is responsible for the management and disposal of Sweden's radioactive waste. It is intended to deposit the spent nuclear fuel in a deep geological repository. This repository shall keep the radiotoxic material separated from humans and the environment for extended periods, from decades to millennia and possibly to geological timescales. During this time perspective climate induced changes such as shore-level displacement and evolution of permafrost and ice sheets are expected to occur which may affect the repository. The possible occurrence, extent and duration of these long-term changes, are therefore of interest when considering the assessment of repository performance and safety. The main climate parameters determining both surface and subsurface conditions are temperature and precipitation. As a result of the last advance of the Weichselian ice sheet only few geological archives exist, which contain information on past climatic conditions in Sweden before c 16,000 years BP. The purpose of this literature review is to compile and evaluate available information from Scandinavian, Northern and Central European geological archives, which record climatic conditions during the Weichselian time period. The compilation provides paleotemperature data sets, which may be used to explore the possible evolution of periglacial permafrost in Sweden. This report is a synopsis of 22 publications detailing climatic and environmental changes during the Weichselian time period in Northwestern Europe based on quantified paleotemperature records. Some of the data is presented as temperature curves which were digitised specifically for this report. The time range covered by the different publications varies considerably. Only few authors dealt with the whole Weichselian period and the majority cover only a few thousand years. This however is not considered to influence the reliability of the archives. The reason for the

  6. Northern European long term climate archives

    International Nuclear Information System (INIS)

    The Swedish Nuclear Fuel and Waste Management Company is responsible for the management and disposal of Sweden's radioactive waste. It is intended to deposit the spent nuclear fuel in a deep geological repository. This repository shall keep the radiotoxic material separated from humans and the environment for extended periods, from decades to millennia and possibly to geological timescales. During this time perspective climate induced changes such as shore-level displacement and evolution of permafrost and ice sheets are expected to occur which may affect the repository. The possible occurrence, extent and duration of these long-term changes, are therefore of interest when considering the assessment of repository performance and safety. The main climate parameters determining both surface and subsurface conditions are temperature and precipitation. As a result of the last advance of the Weichselian ice sheet only few geological archives exist, which contain information on past climatic conditions in Sweden before c 16,000 years BP. The purpose of this literature review is to compile and evaluate available information from Scandinavian, Northern and Central European geological archives, which record climatic conditions during the Weichselian time period. The compilation provides paleotemperature data sets, which may be used to explore the possible evolution of periglacial permafrost in Sweden. This report is a synopsis of 22 publications detailing climatic and environmental changes during the Weichselian time period in Northwestern Europe based on quantified paleotemperature records. Some of the data is presented as temperature curves which were digitised specifically for this report. The time range covered by the different publications varies considerably. Only few authors dealt with the whole Weichselian period and the majority cover only a few thousand years. This however is not considered to influence the reliability of the archives. The reason for the varying

  7. Long-term Treatment in Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Meliha Zengin Eroglu

    2010-08-01

    Full Text Available Although the importance of long-term prophylactic treatment is certain in bipolar disorder, there is stil debate on how to which patients and evaluate the treatment response. Efficacious long-term treatment can reduce morbidity and mortality significantly and improve quality of life of bipolar patients. The concept of ideal response should also be defined very clearly in order to discuss the difficulties of measuring the effectiveness of the prophylactic treatment. The aims of this paper are to determine whether our currently methods and criteria are valid, reliable and sensitive evaluating the efficacy of the treatment response and to briefly inform the clinicians about the drugs used in pharmacologic prophylaxis in accordance with relevant data.

  8. [Taiwan long-term care insurance and the evolution of long-term care in Japan].

    Science.gov (United States)

    Huang, Hui-Wen; Liu, Shu-Hui; Pai, Yu-Chu

    2010-08-01

    The proportion of elderly (65 years of age and older) in Taiwan has exceeded 10% since 2008. With more elderly, the number of patients suffering from dementia and disabilities has also been rapidly increasing. Japan also has been facing increasing demand for long-term care due to an aging society. Prior to 2000, social welfare programs in Japan, working to cope with changing needs, typically provided insufficient services, and geriatric patients were hospitalized unnecessarily, wasting medical resources and causing undue patient hardship. In response, Japan launched its long-term care insurance program in April 2000. Under the program, city, town and village-based organizations should take responsibility for providing care to the elderly in their place of residence. The program significantly improved previous financial shortfalls and long-term care supply and demand has been met by existing social welfare organization resources. In Taiwan, the provision of long-term care by county / city authorities has proven inconsistent, with performance deemed poor after its first decade of long-term care operations. Service was found to be affected by differences in available resources and insufficient long-term care administration. The cultures of Taiwan and Japan are similar. The authors visited the Japan Long-Term Care Insurance Institute in August 2009. Main issues involved in the implementation and evolution of the Japan long-term Care Insurance are reported on in this paper. We hope such may be useful information to those working to develop long-term care programs in Taiwan. PMID:20661859

  9. Long term complications in juvenile diabetes mellitus

    OpenAIRE

    Nordwall, Maria

    2006-01-01

    Background/aim. The incidence of microvascular complications has been reported to be unchanged the last decades. However, in randomized clinical trials it has been shown that improved metabolic control can reduce the development of long term complications. It has been debated whether it is possible to achieve the same results in an unselected population. In a previous study we found a decreased incidence of overt nephropathy, but unchanged incidence of severe laser treated retinopathy in a po...

  10. Clinical review: Long-term noninvasive ventilation

    OpenAIRE

    Robert, Dominique; Argaud, Laurent

    2007-01-01

    Noninvasive positive ventilation has undergone a remarkable evolution over the past decades and is assuming an important role in the management of both acute and chronic respiratory failure. Long-term ventilatory support should be considered a standard of care to treat selected patients following an intensive care unit (ICU) stay. In this setting, appropriate use of noninvasive ventilation can be expected to improve patient outcomes, reduce ICU admission, enhance patient comfort, and increase...

  11. Have long-term inflation expectations declined?

    OpenAIRE

    Nechio, Fernanda

    2015-01-01

    Based on surveys of professional forecasters, expectations for price inflation 5 to 10 years ahead have edged down over the past few years. This decline seems to be primarily driven by revised expectations from forecasters who overestimated inflation in the aftermath of the Great Recession. Currently, the median survey-based expectation for long-term inflation is close to its pre-recession level and appears well anchored at the Fed’s 2% longer-run inflation objective.

  12. Long term prognosis of reactive salmonella arthritis

    OpenAIRE

    Leirisalo-Repo, M; Helenius, P; Hannu, T; Lehtinen, A; Kreula, J; Taavitsainen, M; Koskimies, S

    1997-01-01

    OBJECTIVES—Reactive joint complications triggered by salmonella gastroenteritis are increasingly reported, but the outcome and long term prognosis of the patients is incompletely known. This study looked at the prognosis of salmonella arthritis in patients hospitalised in 1970-1986.
METHODS—Hospital records from two hospitals in southern Finland were screened for patients with the discharge diagnosis of salmonellosis or reactive, postinfectious arthritis or Reiter's disease. For the patients ...

  13. Long-term consequences of anorexia nervosa.

    Science.gov (United States)

    Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Katulski, Krzysztof

    2013-07-01

    Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed. PMID:23706279

  14. Long Term Evolution of Plasma Wakefields

    OpenAIRE

    Sahai, Aakash A.; Katsouleas, T. C.; Tsung, F. S.; Mori, W. B.

    2014-01-01

    We study the long-term evolution (LTE) of plasma wakefields over multiple plasma-electron periods and few plasma-ion periods, much less than a recombination time. The evolution and relaxation of such a wakefield-perturbed plasma over these timescales has important implications for the upper limits of repetition-rates in plasma colliders. Intense fields in relativistic lasers (or intense beams) create plasma wakefields (modes around {\\omega}pe) by transferring energy to the plasma electrons. C...

  15. Long term evolution 4G and beyond

    CERN Document Server

    Yacoub, Michel; Figueiredo, Fabrício; Tronco, Tania

    2016-01-01

    This book focus on Long Term Evolution (LTE) and beyond. The chapters describe different aspects of research and development in LTE, LTE-Advanced (4G systems) and LTE-450 MHz such as telecommunications regulatory framework, voice over LTE, link adaptation, power control, interference mitigation mechanisms, performance evaluation for different types of antennas, cognitive mesh network, integration of LTE network and satellite, test environment, power amplifiers and so on. It is useful for researchers in the field of mobile communications.

  16. Energy: solutions for the long term

    International Nuclear Information System (INIS)

    'Power towers' operated by sunlight, vertical-axis, windmills capable of generating electricity, breeder reactors producing more uranium than they consume, and power plants fuelled by nuclear fusion - these are some of the exotic energy sources to be created as long term alternatives under the U.S. Government's plan for energy and research development. International co-operation, which has already begun, could permit other nations to share with America the fruits of this investment in the future

  17. Long-term course of opioid addiction.

    Science.gov (United States)

    Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

    2015-01-01

    Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed. PMID:25747921

  18. Long term nuclear programme for Australia

    International Nuclear Information System (INIS)

    While it is difficult at this time to foreshadow a long term nuclear programme for Australia, the essential ingredients of the decision-making back-ground have been set out. The first involvement in the nuclear scene appears to be an entry as a uranium supplier in the late 1970s, though no indigenous use of uranium as a fuel is foreseen until after 1990. (J.R.)

  19. Managing soils for long-term productivity

    OpenAIRE

    Syers, J. K.

    1997-01-01

    Meeting the goal of long-term agricultural productivity requires that soil degradation be halted and reversed. Soil fertility decline is a key factor in soil degradation and is probably the major cause of declining crop yields. There is evidence that the contribution of declining soil fertility to soil degradation has been underestimated. Sensitivity to soil degradation is implicit in the assessment of the sustainability of land management practices, with wide recognition of the fact that soi...

  20. Timber joints under long-term loading

    DEFF Research Database (Denmark)

    Feldborg, T.; Johansen, M.

    This report describes tests and results from stiffness and strength testing of splice joints under long-term loading. During two years of loading the spicimens were exposed to cyclically changing relative humidity. After the loading period the specimens were short-term tested. The connectors were...... integral nail-plates and nailed steel and plywood gussets. The report is intended for designers and researchers in timber engineering....

  1. Long-term reductions in tinnitus severity

    OpenAIRE

    Folmer Robert L

    2002-01-01

    Abstract Background This study was undertaken to assess long-term changes in tinnitus severity exhibited by patients who completed a comprehensive tinnitus management program; to identify factors that contributed to changes in tinnitus severity within this population; to contribute to the development and refinement of effective assessment and management procedures for tinnitus. Methods Detailed questionnaires were mailed to 300 consecutive patients prior to their initial appointment at the Or...

  2. Long-term reductions in tinnitus severity

    OpenAIRE

    Folmer, Robert L.

    2002-01-01

    Background This study was undertaken to assess long-term changes in tinnitus severity exhibited by patients who completed a comprehensive tinnitus management program; to identify factors that contributed to changes in tinnitus severity within this population; to contribute to the development and refinement of effective assessment and management procedures for tinnitus. Methods Detailed questionnaires were mailed to 300 consecutive patients prior to their initial appointment at the Oregon Heal...

  3. Procrastination on Long-Term Projects

    OpenAIRE

    O'Donoghue, Ted; Rabin, Matthew

    2002-01-01

    Previous papers on time-inconsistent procrastination assume projects are completed once begun. We develop a model in which a person chooses whether and when to complete each stage of a long-term project. In addition to procrastination in starting a project, a naive person might undertake costly effort to begin a project but then never complete it. When the costs of completing different stages are more unequal, procrastination is more likely, and it is when later stages are more costly that ...

  4. Long-Term Trends in World Politics

    Directory of Open Access Journals (Sweden)

    George Modelski

    2015-08-01

    Full Text Available A revisit, and an extension, of the paper “From Leadership to Organization: The Evolution of Global Politics,” originally presented at the University of Zurich in 1993. Three long-term processes: the evolution of global politics (or political globalization; the rise and decline of world powers (the long cycle of global politics; and the emergence of the world system, have been reviewed and updated.

  5. Long-term orbital lifetime predictions

    Science.gov (United States)

    Dreher, P. E.; Lyons, A. T.

    1990-10-01

    Long-term orbital lifetime predictions are analyzed. Predictions were made for three satellites: the Solar Max Mission (SMM), the Long Duration Exposure Facility (LDEF), and the Pegasus Boiler Plate (BP). A technique is discussed for determining an appropriate ballistic coefficient to use in the lifetime prediction. The orbital decay rate should be monitored regularly. Ballistic coefficient updates should be done whenever there is a significant change in the actual decay rate or in the solar activity prediction.

  6. Titanium for long-term tritium storage

    Energy Technology Data Exchange (ETDEWEB)

    Heung, L.K.

    1994-12-01

    Due to the reduction of nuclear weapon stockpile, there will be an excess of tritium returned from the field. The excess tritium needs to be stored for future use, which might be several years away. A safe and cost effective means for long term storage of tritium is needed. Storing tritium in a solid metal tritide is preferred to storing tritium as a gas, because a metal tritide can store tritium in a compact form and the stored tritium will not be released until heat is applied to increase its temperature to several hundred degrees centigrade. Storing tritium as a tritide is safer and more cost effective than as a gas. Several candidate metal hydride materials have been evaluated for long term tritium storage. They include uranium, La-Ni-Al alloys, zirconium and titanium. The criteria used include material cost, radioactivity, stability to air, storage capacity, storage pressure, loading and unloading conditions, and helium retention. Titanium has the best combination of properties and is recommended for long term tritium storage.

  7. [Long-term survival after severe trauma].

    Science.gov (United States)

    Mutschler, W; Mutschler, M; Graw, M; Lefering, R

    2016-07-01

    Long-term survival after severe trauma is rarely addressed in German trauma journals although knowledge of life expectancy and identification of factors contributing to increased mortality are important for lifetime care management, development of service models, and targeting health promotion and prevention interventions. As reliable data in Germany are lacking, we compiled data mainly from the USA and Australia to describe life expectancy, risk factors, and predictors of outcome in patients experiencing traumatic spinal cord injury, traumatic brain injury, and polytrauma. Two years after trauma, life expectancy in all three categories was significantly lower than that of the general population. It depends strongly on severity of disability, age, and gender and is quantifiable. Whereas improvements in medical care have led to a marked decline in short-term mortality, surprisingly long-term survival in severe trauma has not changed over the past 30 years. Therefore, there is need to intensify long-term trauma patient care and to find new strategies to limit primary damage. PMID:27342106

  8. The Effect of Therapeutic Blockades of Dust Particles-Induced Ca2+ Signaling and Proinflammatory Cytokine IL-8 in Human Bronchial Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Ju Hee Yoon

    2015-01-01

    Full Text Available Bronchial epithelial cells are the first barrier of defense against respiratory pathogens. Dust particles as extracellular stimuli are associated with inflammatory reactions after inhalation. It has been reported that dust particles induce intracellular Ca2+ signal, which subsequently increases cytokines production such as interleukin- (IL- 8. However, the study of therapeutic blockades of Ca2+ signaling induced by dust particles in human bronchial epithelial cells is poorly understood. We investigated how to modulate dust particles-induced Ca2+ signaling and proinflammatory cytokine IL-8 expression. Bronchial epithelial BEAS-2B cells were exposed to PM10 dust particles and subsequent mediated intracellular Ca2+ signaling and reactive oxygen species signal. Our results show that exposure to several inhibitors of Ca2+ pathway attenuated the PM10-induced Ca2+ response and subsequent IL-8 mRNA expression. PM10-mediated Ca2+ signal and IL-8 expression were attenuated by several pharmacological blockades such as antioxidants, IP3-PLC blockers, and TRPM2 inhibitors. Our results show that blockades of PLC or TRPM2 reduced both of PM10-mediated Ca2+ signal and IL-8 expression, suggesting that treatment with these blockades should be considered for potential therapeutic trials in pulmonary epithelium for inflammation caused by environmental events such as seasonal dust storm.

  9. Long-term Administration Induced P-glycoprotein-mediated Drug Resistance at Blood-Brain Barrier%长期用药在血脑屏障上诱导P-糖蛋白介导的耐药性

    Institute of Scientific and Technical Information of China (English)

    何玲; 张陆勇; 刘国卿

    2003-01-01

    目的:考察长期用药在血脑屏障上是否引起耐药性及P-糖蛋白(P-gp)表达增强.方法:原代牛脑微血管内皮细胞(BCEC)加入环孢素A(CsA),长春新碱(VCR),阿霉素(Dox),或粉防己碱(Tet),初始剂量分别为0.0083,0.091,0.34,或0.32 μmol/L,培养至传代剂量翻倍.连续作用21,37,51或69 d后,用罗丹明123(Rh123)检测P-gp功能.将各药物诱导69天的BCEC制膜,用酶联免疫吸附法(ELISA)测定P-gp表达.结果:Dox用药37 d使胞内Rh123浓度降低38%.连续给药51和69 d后,Dox分别使胞内Rh123浓度降低47%和57%,VCR组分别降低36%和40%.而CsA和Tet组一直未见明显变化.维拉帕米(10μmol/L)分别使CsA、Tet、Dox和VCR诱导组BCEC内Rh123的摄取增加92%、85%、143%和186%.Dox和VCR连续用药69 d使P-gp的表达增强45%和32%.结论:长期使用Dox或VCR可在血脑屏障上诱导P-gp介导的耐药性以及P-gp表达增强.%AIM: To study whether long-term administration could induce drug resistance and P-glycoprotein(P-gp) expression at blood-brain barrier(BBB). METHOD: Primary bovine brain capillary endothelial cells(BCECs) were cultured in the presence of cyclosporin A(CsA),vincrinstine(VCR),doxorubicin(Dox),or tetrandrine(Tet) at the original concentration of 0.0083,0.091,0.34,or 0.32 μmol/L,respectively. The drug was maintained until the BCECs approached confluence,at which point the subculture and doubling of drug would be repeated,and the whole process continued through 4-5 cycles. Using rhodamine 123(Rh123) to examine the functional activity of P-gp expressed in drug-treated BCECs after a period of 21,37,51,and 69 d respectively. The plasma membranes of BCECs pretreated with inducing drug for 69 d were isolated and prepared,and the P-gp expression in the plasma membranes was detected by enzyme-linked immunosorbent assay(ELISA). RESULT: No significant change in P-gp function was observed in comparison with the control on d21. Administration of Dox obviously decreased the

  10. AT1 receptor blockade attenuates insulin resistance and myocardial remodeling in rats with diet-induced obesity.

    Directory of Open Access Journals (Sweden)

    Silvio A Oliveira-Junior

    Full Text Available BACKGROUND: Although obesity has been associated with metabolic and cardiac disturbances, the carrier mechanisms for these responses are poorly understood. This study analyzed whether angiotensin II blockade attenuates metabolic and cardiovascular disorders in rats with diet-induced obesity. MATERIAL AND METHODS: Wistar-Kyoto (n = 40 rats were subjected to control (C; 3.2 kcal/g and hypercaloric diets (OB; 4.6 kcal/g for 30 weeks. Subsequently, rats were distributed to four groups: C, CL, OB, and OBL. L groups received Losartan (30 mg/kg/day for five weeks. After this period we performed in vivo glucose tolerance and insulin tolerance tests, and measured triacylglycerol, insulin, angiotensin-converting enzyme activity (ACE, and leptin levels. Cardiovascular analyzes included systolic blood pressure (SBP, echocardiography, myocardial morphometric study, myosin heavy chain composition, and measurements of myocardial protein levels of angiotensin, extracellular signal-regulated (ERK1/2, c-Jun amino-terminal kinases (JNK, insulin receptor subunit β (βIR, and phosphatidylinositol 3-kinase (PI3K by Western Blot. RESULTS: Glucose metabolism, insulin, lipid, and ACE activity disorders observed with obesity were minimized by Losartan. Moreover, obesity was associated with increased SBP, myocardial hypertrophy, interstitial fibrosis and improved systolic performance; these effects were also minimized with Losartan. On a molecular level, OB exhibited higher ERK, Tyr-phosphorylated βIR, and PI3K expression, and reduced myocardial angiotensin and JNK expression. ERK and JNK expression were regulated in the presence of Losartan, while angiotensin, Tyr-βRI, total and Tyr-phosphorylated PI3K expression were elevated in the OBL group. CONCLUSION: Angiotensin II blockade with Losartan attenuates obesity-induced metabolic and cardiovascular changes.

  11. Long-term Study of a Quadrivalent Human Papillomavirus Vaccine

    DEFF Research Database (Denmark)

    Ferris, Daron; Samakoses, Rudiwilai; Block, Stan L;

    2014-01-01

    BACKGROUND: We present a long-term safety, immunogenicity, and effectiveness study of a quadrivalent human papillomavirus (HPV4) vaccine. METHODS: Sexually naive boys and girls aged 9 to 15 years (N = 1781) were assigned (2:1) to receive HPV4 vaccine or saline placebo at day 1 and months 2 and 6....... At month 30, the placebo group (n = 482) received HPV4 vaccine following the same regimen and both cohorts were followed through month 96. Subjects ≥16 years were eligible for effectiveness evaluations. The primary objective was to evaluate the long-term anti-HPV6/11/16/18 serological levels. The...... secondary objective was to estimate vaccine effectiveness against HPV6/11/16/18-related persistent infection or disease. RESULTS: For each of the HPV4 vaccine types, vaccination-induced anti-HPV response persisted through month 96. Among 429 subjects who received HPV4 vaccine at a mean age of 12, none...

  12. Long-term ecophysiological responses to climate change

    DEFF Research Database (Denmark)

    Boesgaard, Kristine Stove; Ro-Poulsen, Helge

    Plant physiology is affected by climate change. Acclimations of photosynthetic processes are induced by short-term changes in climatic conditions. Further acclimation can be caused by longterm adjustments to climate change due to ecosystem-feedbacks. The aim of this PhD was to investigate plant...... physiological responses to climate change in a seasonal and long-term perspective. The effects of elevated CO2, passive night time warming and periodic summer drought as single factor and in combination, on plant physiology were investigated in the long-term multifactorial field experiment CLIMAITE in a Danish...... term responses of plant physiology to the climate change factors were investigated. In the CLIMAITE-experiment it has been shown that 2 years of treatment altered physiological responses in Deschampsiaand Calluna. In the work of this PhD similar responses were observed after 6 years of treatment...

  13. SGK Protein Kinase Facilitates the Expression of Long-Term Potentiation in Hippocampal Neurons

    Science.gov (United States)

    Ma, Yun L.; Tsai, Ming C.; Hsu, Wei L.; Lee, Eminy H.Y.

    2006-01-01

    Previous studies showed that the serum- and glucocorticoid-inducible kinase ("sgk") gene plays an important role in long-term memory formation. The present study further examined the role of SGK in long-term potentiation (LTP). The dominant-negative mutant of "sgk," SGKS422A, was used to inactivate SGK. Results revealed a time-dependent increase…

  14. Radio-induced breast cancers exhibiting aggressive anatomo-pathological characteristics: retrospective study of the long-term follow-up committee of the French Society of Child Cancers; Cancers du sein radio-induits presentant des caracteristiques anatomopathologiques agressives: etude retrospective du comite de suivi a long terme de la Societe francaise des cancers de l'enfant

    Energy Technology Data Exchange (ETDEWEB)

    Demoor, C.; Mahe, M.A.; Supiot, S. [ICO Rene-Gauducheau, Nantes (France); Vathaire, F. de [Inserm UMRS 1018, institut de cancerologie Gustave-Roussy, Villejuif (France); Oberlin, O. [Institut de cancerologie Gustave-Roussy, Villejuif (France); Noel, G. [Centre Paul-Strauss, Strasbourg (France); Brillaud, V. [Institut Bergonie, Bordeaux (France); Bernier, V. [Centre Alexis-Vautrin, Nancy (France); Laprie, A. [Institut Claudius-Regaud, Toulouse (France); Claude, L. [Centre Leon-Berard, Lyon (France)

    2011-10-15

    The authors report an analysis of clinical-pathological characteristics of radio-induced breast cancers registered in six French centres. 82 breast cancers concerning 75 women have been analyzed in terms of patient age, cancer type, interval between both cancers. It appears that radio-induced cancers exhibited significantly more aggressive characteristics. The screening of young women at risk is therefore recommended for an early diagnosis and treatment. Short communication

  15. Long term evolution of spent nuclear fuel in long term storage or geological disposal. Status of the French research program PRECCI

    International Nuclear Information System (INIS)

    This paper aims to give a brief overview of the wide research undertaken in France in order to elucidate the potential long term evolution of spent nuclear fuels in long term storage or geological disposal. A particular emphasis is put on the last scientific results obtained and on the major scientific issue on which R and D is currently focused: the fate of helium, the RN migration within the rod (irradiation-induced diffusion) and the cladding long term creep for the closed system evolution, the kinetics of oxidation and the RN source term for the evolution in gaseous atmosphere, and the radiolytic dissolution and RN source term in presence of water. (author)

  16. Timber beams subjected to long - term loading

    Science.gov (United States)

    Sógel, K.

    2010-09-01

    Wood is a significant structural material, which is often used for timber bearing structures. Elements of timber structures must especially satisfy safety requirements, which are expressed by the ultimate limit states in the established standards. The structure must also satisfy the serviceability limit states. Local and global deformations make it impossible for the structure to serve the purpose it was designed for. It is important to take the deflections and their possible increase into account in the design to provide a structure which can be used during the whole period of service. Based on earlier examinations, it is known that a timber element over the course of long-term loading shows creep behavior. The structure of wood is able to adapt to the conditions of the surrounding environment. The properties of wood are especially affected by the relative humidity of the air and then by the type, intensity and duration of the loading. The most important factors affecting the serviceability of timber structures are volume changes caused by humidity and additional deflections caused by the effects of long-term loading. These phenomena emphasize the importance of serviceability limit states for timber structures. The paper deals with a long-term experimental investigation of timber girders that are currently often used. The aim was to obtain the deflection curves and mark the time dependence and the final deflections. The paper will also define the approximations for simulating the time-dependent deflections and obtain the creep coefficients for calculating the final deflections of the girders investigated.

  17. Long Term R&D for Safeguards

    International Nuclear Information System (INIS)

    Within the Office of Defense Nuclear Non-proliferation Research and Development (DNN R&D), the Nuclear Weapons and Material Security Team conducts research to develop advanced detection and source technologies for the purposes of detecting and characterizing special nuclear materials (SNM); international safeguards and radiological source replacement; nuclear arms control treaty monitoring and verification; and supporting interdiction and nuclear security efforts across NNSA. Our safeguards-specific goal is to develop and demonstrate new technologies and capabilities to cooperatively quantify and track SNM in the nuclear fuel cycle and detect any diversion of these materials for illicit purposes. Our goals and objectives align with a technology goal of the International Atomic Energy's Long Term Strategy for 2012-2023 ''to improve the Department's technical capabilities by making use of scientific and technological innovation, and to enhance its readiness to safeguard new nuclear technology and support new verification missions.'' Toward that end, we work closely with the US Department of Energy's Next Generation Safeguards Initiative and the US Support Programme to meet their specific long term needs. In this talk we will give a brief overview of current research efforts and specifically describe several helium-3 replacement technologies, advanced spent nuclear fuel characterization methods, and upcoming tags and seals technologies. We will present additional research into cross cutting enabling technologies such as advancements in detector materials, electronics, and sources, and basic physics measurements that support long term safeguards R&D. (author)

  18. Long-term governance for sustainability

    International Nuclear Information System (INIS)

    Meritxell Martell spoke of the long-term aspects of radioactive waste management. She pointed out that decision-making processes need to be framed within the context of sustainability, which means that a balance should be sought between scientific considerations, economic aspects and structural conditions. Focusing on structural aspects, Working Group 3 of COWAM-Spain came to the conclusion that the activity of the regulator is a key factor of long-term management. Another finding is that from a sustainability perspective multi-level governance is more effective for coping with the challenges of radioactive waste management than one tier of government-making decisions. The working group also felt that the current Local Information Committees need to evolve towards more institutionalized and legitimized mechanisms for long-term involvement. Ms. Martell introduced a study comparing the efficiency of economic instruments to advance sustainable development in nuclear communities vs. municipalities in mining areas. The study found that funds transferred to nuclear zones had become a means to facilitate local acceptance of nuclear facilities rather than a means to promote socio-economic development. Another finding is that economic instruments are not sufficient guarantees of sustainable development by themselves; additional preconditions include leadership, vision and entrepreneur-ship on the part of community leaders, private or public investments, among others. Finally, Ms. Martell summarised the challenges faced by the Spanish radioactive waste management programme, which include the need for strategic thinking, designing the future in a participatory fashion, and working with local and regional governments and citizens to devise mechanisms for social learning, economic development and environmental protection. (author)

  19. LTE (4G) – Long Term Evolution

    OpenAIRE

    Juhala, Arttu

    2014-01-01

    Tässä opinnäytetyössä käsitellään matkapuhelinverkko teknologian neljättä sukupolvea ja tarkemmin Long Term Evolutionia eli LTE:tä. Tutustutaan 4G LTE – matkapuhelinverkon historiaan, teknologian kehitykseen ja rakenteeseen. Lisäksi esitellään tarkemmin tekniikoita, joita LTE käyttää. Työssä on tehty pienimuotoinen mittausesimerkki pakettidatan siirrosta signaali analysaattorilla, sekä testattu käytännössä operaattorin tarjoamaa rajatonta 4G liittymää Tampereen keskustassa. Lopuksi työssä ver...

  20. Long-term effects of class size

    OpenAIRE

    Fredriksson, Peter; Öckert, Björn; Oosterbeek, Hessel

    2012-01-01

    This paper evaluates the long-term effects of class size in primary school. We use rich administrative data from Sweden and exploit variation in class size created by a maximum class size rule. Smaller classes in the last three years of primary school (age 10 to 13) are not only beneficial for cognitive test scores at age 13 but also for non-cognitive scores at that age, for cognitive test scores at ages 16 and 18, and for completed education and wages at age 27 to 42. The estimated effect on...

  1. Long-Term Effects of Class Size

    OpenAIRE

    Fredriksson, Peter; Öckert, Björn; Oosterbeek, Hessel

    2011-01-01

    This paper evaluates the long-term effects of class size in primary school. We use rich administrative data from Sweden and exploit variation in class size created by a maximum class size rule. Smaller classes in the last three years of primary school (age 10 to 13) are not only beneficial for cognitive test scores at age 13 but also for non-cognitive scores at that age, for cognitive test scores at ages 16 and 18, and for completed education and wages at age 27 to 42. The estimated effect on...

  2. Long-term effects of class size

    OpenAIRE

    Fredriksson, Peter; Öckert, Björn; Oosterbeek, Hessel

    2011-01-01

    This paper evaluates the long-term effects of class size in primary school. We use rich administrative data from Sweden and exploit variation in class size created by a maximum class size rule. Smaller classes in the last three years of primary school (age 10 to 13) are not only beneficial for cognitive test scores at age 13 but also for non-cognitive scores at that age, for cognitive test scores at ages 16 and 18, and for completed education and wages at age 27 to 42. The estimated effect on...

  3. Long-term effects of class size

    OpenAIRE

    Fredriksson, Peter; Öckert, Björn; Oosterbeek, Hessel

    2012-01-01

    This paper evaluates the long-term effects of class size in primary school. We use rich data from Sweden and exploit variation in class size created by a maximum class size rule. Smaller classes in the last three years of primary school (age 10 to 13) are beneficial for cognitive and non-cognitive ability at age 13, and improve achievement at age 16. Most importantly, we find that smaller classes have positive effects on completed education, wages, and earnings at age 27 to 42. The estimated ...

  4. Declining Long-Term Employment in Japan

    OpenAIRE

    KAWAGUCHI Daiji; UENO Yuko

    2011-01-01

    This paper documents the secular decline of years of job tenure in Japan based on micro data from two representative government surveys, namely the household-based Employment Status Survey (ESS) and the establishment-based Basic Survey of Wage Structure (BSWS). Workers born in 1970 have experienced about 20 percent fewer years of job tenure than those born in 1945, based on an analysis of ESS data. The decline of the long-term employment relationship is uniformly observed across firm sizes an...

  5. The long-term stability of becquerelite

    International Nuclear Information System (INIS)

    Uranium-series disequilibria data, in conjunction with petrographic analyses, indicate that the uranyl oxide hydrate becquerelite can persist for hundreds of thousands of years, possibly longer. Becquerelite probably forms continuously as ground water compositions permit and is resistant to U leaching by ground water. On the time scale of interest for the geologic disposal of spent UO2 nuclear fuel, becquerelite is a long-lived sink for uranium in oxidizing, U and Ca-bearing ground waters. Such long-term stability also supports recent solubility experiments that indicate natural becquerelite has a lower solubility product than that determined for synthetic becquerelites

  6. Long Term Archiving and CCSDS Standards

    Science.gov (United States)

    Boucon, Danièle

    This article presents some conceptual and implementation CCSDS -Consultative Committee for Space Data Systemsstandards for long term archiving. It focuses on the most recent one, the Producer Archive Interface Specification (PAIS) standard. This standard, currently available as a draft on the CCSDS web site, will be published by the beginning of 2014. It will enable the Producer to share with the Archive a sufficiently precise and unambiguous formal definition of the Digital Objects to be produced and transferred, by means of a model. It will also enable a precise definition of the packaging of these objects in the form of Submission Information Packages (SIPs), including the order in which they should be transferred.

  7. The long term stability of lidar calibrations

    DEFF Research Database (Denmark)

    Courtney, Michael; Gayle Nygaard, Nicolai

    Wind lidars are now used extensively for wind resource measurements. One of the requirements for the data to be accepted in support of project financing (so-called ‘banka-bility’) is to demonstrate the long-term stability of lidar cali-brations. Calibration results for six Leosphere WindCube li-dars......-ters pertaining in the different calibration periods. This is supported by sliding-window analyses of one lidar at one location where the same order of variation is observed as between pre-service and post-service calibrations....

  8. Long term youth unemployment or disposable workforce?

    OpenAIRE

    Bruno Contini; Elisa Grand

    2010-01-01

    This paper explores a process which I denote as “young workforce disposal” (YWD). YWD reflects the fact that many young people enter the labor market as dependent employees, at some later time they are dismissed and (presumably) move into never-ending unemployment. Long term unemployment may last two, three, four years, but, in the end, it should lead to re-entry in working activities. If it does not, i.e. if we observe young men separating from their jobs for whatever reason, and, for as lon...

  9. Long Term Durability of Glass Reinforced Composites

    OpenAIRE

    Cain, Jason James

    2008-01-01

    This dissertation discusses topics related to the performance and long-term durability of glass-reinforced composites. The first portion of this dissertation describes work to assess the effect that post-curing has on widely used E-glass/vinyl-ester composites (E-glass/Derakane 510-A and E-glass/Derakane 8084). It is shown that post-curing can have significant positive effects on the initial material properties of glass-reinforced vinyl ester composites. Furthermore, the post-cure of 82Â...

  10. Human Behaviour in Long-Term Missions

    Science.gov (United States)

    1997-01-01

    In this session, Session WP1, the discussion focuses on the following topics: Psychological Support for International Space Station Mission; Psycho-social Training for Man in Space; Study of the Physiological Adaptation of the Crew During A 135-Day Space Simulation; Interpersonal Relationships in Space Simulation, The Long-Term Bed Rest in Head-Down Tilt Position; Psychological Adaptation in Groups of Varying Sizes and Environments; Deviance Among Expeditioners, Defining the Off-Nominal Act in Space and Polar Field Analogs; Getting Effective Sleep in the Space-Station Environment; Human Sleep and Circadian Rhythms are Altered During Spaceflight; and Methodological Approach to Study of Cosmonauts Errors and Its Instrumental Support.

  11. Long-term plant availability of actinides

    International Nuclear Information System (INIS)

    Environmental releases of actinide elements raise issues about which data are very limited. Quantitative information is required to assess the long-term behavior of actinides and their potential hazards resulting from the transport through food chains leading to man. Of special interest is the effect of time on the changes in the availability of actinide elements for uptake by plants from soil. This study provides valuable information on the effects of weathering and aging on the uptake of actinides from soil by range and crop plants grown under realistic field conditions

  12. P2X7 receptor blockade protects against cisplatin-induced nephrotoxicity in mice by decreasing the activities of inflammasome components, oxidative stress and caspase-3

    International Nuclear Information System (INIS)

    Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. The purinergic 2X7 receptor (P2X7R) plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the expression of P2X7R in cisplatin-induced nephrotoxicity in C57BL/6 mice, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after P2X7R blockade in vivo using an antagonist A-438079. Moreover, we measured the changes of nod-like receptor family, pyrin domain containing proteins (NLRP3) inflammasome components, oxidative stress, and proapoptotic genes in renal tissues in cisplatin-induced nephrotoxicity after treatment with A-438079. We found that the expression of P2X7R was significantly upregulated in the renal tubular epithelial cells in cisplatin-induced nephrotoxicity compared with that of the normal control group. Furthermore, pretreatment with A-438079 markedly attenuated the cisplatin-induced renal injury while lightening the histological damage, inflammatory response and apoptosis in renal tissue, and improved the renal function. These effects were associated with the significantly reduced levels of NLRP3 inflammasome components, oxidative stress, p53 and caspase-3 in renal tissues in cisplatin-induced nephrotoxicity. In conclusions, our studies suggest that the upregulated activity of P2X7R might play important roles in the development of cisplatin-induced nephrotoxicity, and P2X7R blockade might become an effective therapeutic strategy for this disease. - Highlights: • The P2X7R expression was markedly upregulated in cisplatin-induced nephrotoxicity. • P2X7R blockade significantly attenuated the cisplatin-induced renal injury. • P2X7R blockade reduced activities of NLRP3 inflammasome components in renal tissue. • P2X7R blockade

  13. P2X7 receptor blockade protects against cisplatin-induced nephrotoxicity in mice by decreasing the activities of inflammasome components, oxidative stress and caspase-3

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yuanyuan; Yuan, Fahuan; Cao, Xuejiao [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China); Zhai, Zhifang [Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Gang Huang [Department of Medical Genetics, Third Military Medical University, Chongqing 430038 (China); Du, Xiang; Wang, Yiqin; Zhang, Jingbo; Huang, Yunjian; Zhao, Jinghong [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China); Hou, Weiping, E-mail: hwp0518@aliyun.com [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China)

    2014-11-15

    Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. The purinergic 2X7 receptor (P2X7R) plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the expression of P2X7R in cisplatin-induced nephrotoxicity in C57BL/6 mice, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after P2X7R blockade in vivo using an antagonist A-438079. Moreover, we measured the changes of nod-like receptor family, pyrin domain containing proteins (NLRP3) inflammasome components, oxidative stress, and proapoptotic genes in renal tissues in cisplatin-induced nephrotoxicity after treatment with A-438079. We found that the expression of P2X7R was significantly upregulated in the renal tubular epithelial cells in cisplatin-induced nephrotoxicity compared with that of the normal control group. Furthermore, pretreatment with A-438079 markedly attenuated the cisplatin-induced renal injury while lightening the histological damage, inflammatory response and apoptosis in renal tissue, and improved the renal function. These effects were associated with the significantly reduced levels of NLRP3 inflammasome components, oxidative stress, p53 and caspase-3 in renal tissues in cisplatin-induced nephrotoxicity. In conclusions, our studies suggest that the upregulated activity of P2X7R might play important roles in the development of cisplatin-induced nephrotoxicity, and P2X7R blockade might become an effective therapeutic strategy for this disease. - Highlights: • The P2X7R expression was markedly upregulated in cisplatin-induced nephrotoxicity. • P2X7R blockade significantly attenuated the cisplatin-induced renal injury. • P2X7R blockade reduced activities of NLRP3 inflammasome components in renal tissue. • P2X7R blockade

  14. Distinct dopamine neurons mediate reward signals for short- and long-term memories

    OpenAIRE

    Yamagata, N; T. Ichinose; Aso, Y; Placais, P.; Friedrich, A.; Sima, R.; Preat, T.; Rubin, G; Tanimoto, H.

    2014-01-01

    Drosophila melanogaster can acquire a stable appetitive olfactory memory when the presentation of a sugar reward and an odor are paired. However, the neuronal mechanisms by which a single training induces long-term memory are poorly understood. Here we show that two distinct subsets of dopamine neurons in the fly brain signal reward for short-term (STM) and long-term memories (LTM). One subset induces memory that decays within several hours, whereas the other induces memory that gradually dev...

  15. Antisense oligonucleotides-induced local blockade of T-bet expression leads to airway inflammation in rats

    Institute of Scientific and Technical Information of China (English)

    Gang WANG; Chun-tao LIU; Zeng-li WANG; Li-li JIANG; Cuniang YAN; Feng-min LUO

    2006-01-01

    Aim: To explore whether local blockade of T-box expressed in T cells (T-bet) expression in the 1ungs could lead to airway inflammation. Methods: Twenty-four rats were randomly divided into 4 groups: saline group, ovalbumin (OVA)-sensitized group, nonsense group, and the antisense group. The OVA-sensitized rats were sensitized and challenged with OVA, and the rats in the nonsense and antisense groups were subjected to an aerosol delivery of the nonsense and antisense oligonucleotides (AS-ODN)of T-bet(0.1%, w/v). The levels of interferon-γ(IFN-γ), interleukin-4(IL-4), and IL-5 in the bronchoalveolar lavage fluid (BALF) were detected by ELISA, and the mRNA and the protein expression of T-bet and GATA-3 genes were examined by in situ hybridization and Western blot analysis, respectively. Results: The expression of T-bet mRNA and protein in the lungs of the rats in the antisense group were inhibited effectively. The lungs of the rats in the antisense and OVA-sensitized groups showed eosinophil and lymphocyte inflammatory infiltration, and eosinophilia located predominantly around the airways. The number of GATA-3 mRNA-positive cells and the level of GAllA-3 protein in the 1ungs of the rats in the antisense and the OVA-sensitized groups significantly increased. The level of IL-4 and IL-5 in the BALF in the antisense and OVA-sensitized groups were elevated, but the level of IFN-γ decreased markedly. Conclusion: Antisense ODN-induced local blockade of T-bet expression leads to airway inflammation with a selective alteration in patterns of cytokine expression and recruitment of eosinophil cells similar to that in the OVA-sensitized

  16. Blockade of Retinol Metabolism Protects T Cell-Induced Hepatitis by Increasing Migration of Regulatory T Cells.

    Science.gov (United States)

    Lee, Young-Sun; Yi, Hyon-Seung; Suh, Yang-Gun; Byun, Jin-Seok; Eun, Hyuk Soo; Kim, So Yeon; Seo, Wonhyo; Jeong, Jong-Min; Choi, Won-Mook; Kim, Myung-Ho; Kim, Ji Hoon; Park, Keun-Gyu; Jeong, Won-Il

    2015-11-01

    Retinols are metabolized into retinoic acids by alcohol dehydrogenase (ADH) and retinaldehyde dehydrogenase (Raldh). However, their roles have yet to be clarified in hepatitis despite enriched retinols in hepatic stellate cells (HSCs). Therefore, we investigated the effects of retinols on Concanavalin A (Con A)-mediated hepatitis. Con A was injected into wild type (WT), Raldh1 knock-out (Raldh1(-/-)), CCL2(-/-) and CCR2(-/-) mice. For migration study of regulatory T cells (Tregs), we used in vivo and ex vivo adoptive transfer systems. Blockade of retinol metabolism in mice given 4-methylpyrazole, an inhibitor of ADH, and ablated Raldh1 gene manifested increased migration of Tregs, eventually protected against Con A-mediated hepatitis by decreasing interferon-γ in T cells. Moreover, interferon-γ treatment increased the expression of ADH3 and Raldh1, but it suppressed that of CCL2 and IL-6 in HSCs. However, the expression of CCL2 and IL-6 was inversely increased upon the pharmacologic or genetic ablation of ADH3 and Raldh1 in HSCs. Indeed, IL-6 treatment increased CCR2 expression of Tregs. In migration assay, ablated CCR2 in Tregs showed reduced migration to HSCs. In adoptive transfer of Tregs in vivo and ex vivo, Raldh1-deficient mice showed more increased migration of Tregs than WT mice. Furthermore, inhibited retinol metabolism increased survival rate (75%) compared with that of the controls (25%) in Con A-induced hepatitis. These results suggest that blockade of retinol metabolism protects against acute liver injury by increased Treg migration, and it may represent a novel therapeutic strategy to control T cell-mediated acute hepatitis. PMID:26537191

  17. CB1 receptor blockade counters age-induced insulin resistance and metabolic dysfunction.

    Science.gov (United States)

    Lipina, Christopher; Vaanholt, Lobke M; Davidova, Anastasija; Mitchell, Sharon E; Storey-Gordon, Emma; Hambly, Catherine; Irving, Andrew J; Speakman, John R; Hundal, Harinder S

    2016-04-01

    The endocannabinoid system can modulate energy homeostasis by regulating feeding behaviour as well as peripheral energy storage and utilization. Importantly, many of its metabolic actions are mediated through the cannabinoid type 1 receptor (CB1R), whose hyperactivation is associated with obesity and impaired metabolic function. Herein, we explored the effects of administering rimonabant, a selective CB1R inverse agonist, upon key metabolic parameters in young (4 month old) and aged (17 month old) adult male C57BL/6 mice. Daily treatment with rimonabant for 14 days transiently reduced food intake in young and aged mice; however, the anorectic response was more profound in aged animals, coinciding with a substantive loss in body fat mass. Notably, reduced insulin sensitivity in aged skeletal muscle and liver concurred with increased CB1R mRNA abundance. Strikingly, rimonabant was shown to improve glucose tolerance and enhance skeletal muscle and liver insulin sensitivity in aged, but not young, adult mice. Moreover, rimonabant-mediated insulin sensitization in aged adipose tissue coincided with amelioration of low-grade inflammation and repressed lipogenic gene expression. Collectively, our findings indicate a key role for CB1R in aging-related insulin resistance and metabolic dysfunction and highlight CB1R blockade as a potential strategy for combating metabolic disorders associated with aging. PMID:26757949

  18. Resistance to atracurium-induced neuromuscular blockade in patients with intractable seizure disorders treated with anticonvulsants.

    Science.gov (United States)

    Tempelhoff, R; Modica, P A; Jellish, W S; Spitznagel, E L

    1990-12-01

    Previous studies have demonstrated that, with the exception of atracurium, resistance to the neuromuscular blocking effects of various muscle relaxants develops in patients receiving anticonvulsant therapy. We studied the effects of 0.5 mg/kg IV atracurium in 53 neurosurgical patients: 21 nonepileptic patients receiving no anticonvulsant therapy (MED = 0); 14 epileptic patients treated with carbamazepine for years (MED = 1); and 18 epileptic patients treated with carbamazepine plus either phenytoin or valproic acid for years (MED = 2). The evoked compound electromyogram of the adductor pollicis brevis was recorded, and results were analyzed using analysis of covariance, with weight and age as covariables. The onset time was not significantly different among the three groups. Times for recovery of baseline and train-of-four responses to stimuli were significantly shorter in the MED = 1 and MED = 2 groups than in control patients (MED = 0). The recovery index (time between 25% and 75% recovery of baseline electromyogram values) was progressively shorter in the three groups (MED = 0: 8.02 min; MED = 1: 5.93 min; MED = 2: 1.96 min; P less than 0.001). This study demonstrates that atracurium, when used on epileptic patients requiring long-term (that is, years of) anticonvulsant therapy, has a shorter duration of action than when used in nonepileptic patients. PMID:2240640

  19. Long-term environmental behaviour of radionuclides

    International Nuclear Information System (INIS)

    The radioactive pollution of the environment results from the atmospheric nuclear weapons testing (during the mid-years of twentieth century), from the development of the civilian nuclear industry and from accidents such as Chernobyl. Assessing the resulting radiation that humans might receive requires a good understanding of the long-term behaviour of radionuclides in the environment. This document reports on a joint European effort to advance this understanding, 3 multinational projects have been coordinated: PEACE, EPORA and LANDSCAPE. This report proposes an overview of the results obtained and they are presented in 6 different themes: i) redistribution in the soil-plant system, ii) modelling, iii) countermeasures, iv) runoff v) spatial variations, and vi) dose assessment. The long term behaviour of the radionuclides 137Cs, 90Sr and 239-240Pu is studied through various approaches, these approaches range from in-situ experiments designed to exploit past contamination events to laboratory simulations. A broad scope of different ecosystems ranging from arctic and boreal regions down to mediterranean ones has been considered. (A.C.)

  20. Long-Term Care Policy: Singapore's Experience.

    Science.gov (United States)

    Chin, Chee Wei Winston; Phua, Kai-Hong

    2016-01-01

    Singapore, like many developed countries, is facing the challenge of a rapidly aging population and the increasing need to provide long-term care (LTC) services for elderly in the community. The Singapore government's philosophy on care for the elderly is that the family should be the first line of support, and it has relied on voluntary welfare organizations (VWOs) or charities for the bulk of LTC service provision. For LTC financing, it has emphasized the principles of co-payment and targeting of state support to the low-income population through means-tested government subsidies. It has also instituted ElderShield, a national severe disability insurance scheme. This paper discusses some of the challenges facing LTC policy in Singapore, particularly the presence of perverse financial incentives for hospitalization, the pitfalls of over-reliance on VWOs, and the challenges facing informal family caregivers. It discusses the role of private LTC insurance in LTC financing, bearing in mind demand- and supply-side failures that have plagued the private LTC insurance market. It suggests the need for more standardized needs assessment and portable LTC benefits, with reference to the Japanese Long-Term Care Insurance program, and also discusses the need to provide more support to informal family caregivers. PMID:26808468

  1. Long term testing of PSI-membranes

    Energy Technology Data Exchange (ETDEWEB)

    Huslage, J.; Brack, H.P.; Geiger, F.; Buechi, F.N.; Tsukada, A.; Scherer, G.G. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1999-08-01

    Long term tests of PSI membranes based on radiation-grafted FEP and ETFE films were carried out and FEP-based membranes were evaluated by monitoring the in-situ membrane area resistance measured by a current pulse method. By modifying our irradiation procedure and using the double crosslinking concept we obtain reproducible membrane cell lifetimes (in term of in-situ membrane resistance) of greater than 5000 hours at 60-65{sup o}C. Preliminary tests at 80-85{sup o}C with lifetimes of greater than 2500 demonstrate the potential long term stability of PSI proton exchange membranes based on FEP over the whole operating temperature range of low-temperature polymer electrolyte fuel cells. Radiation grafted PSI membranes based on ETFE have better mechanical properties than those of the FEP membranes. Mechanical properties are particularly important in large area cells and fuel cell stacks. ETFE membranes have been tested successfully for approximately 1000 h in a 2-cell stack (100 cm{sup 2} active area each cell). (author) 4 figs., 4 refs.

  2. Long-term environmental behaviour of radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Brechignac, F.; Moberg, L.; Suomela, M

    2000-04-01

    The radioactive pollution of the environment results from the atmospheric nuclear weapons testing (during the mid-years of twentieth century), from the development of the civilian nuclear industry and from accidents such as Chernobyl. Assessing the resulting radiation that humans might receive requires a good understanding of the long-term behaviour of radionuclides in the environment. This document reports on a joint European effort to advance this understanding, 3 multinational projects have been coordinated: PEACE, EPORA and LANDSCAPE. This report proposes an overview of the results obtained and they are presented in 6 different themes: (i) redistribution in the soil-plant system, (ii) modelling, (iii) countermeasures, (iv) runoff (v) spatial variations, and (vi) dose assessment. The long term behaviour of the radionuclides {sup 137}Cs, {sup 90}Sr and {sup 239-240}Pu is studied through various approaches, these approaches range from in-situ experiments designed to exploit past contamination events to laboratory simulations. A broad scope of different ecosystems ranging from arctic and boreal regions down to mediterranean ones has been considered. (A.C.)

  3. Long term changes in the polar vortices

    Science.gov (United States)

    Braathen, Geir O.

    2015-04-01

    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented.

  4. The evolution of an asymmetric deltaic lobe (Sf. Gheorghe, Danube) in association with cyclic development of the river-mouth bar: Long-term pattern and present adaptations to human-induced sediment depletion

    Science.gov (United States)

    Preoteasa, Luminiţa; Vespremeanu-Stroe, Alfred; Tătui, Florin; Zăinescu, Florin; Timar-Gabor, Alida; Cîrdan, Ionela

    2016-01-01

    constant at c.10 m/year. Abrupt changes occurred within the last cycle (since the beginning of the 20th century) as a consequence of human-induced depletion of sediment supplied by the Danube flow, and is mainly expressed by the complete cessation of the updrift coastal progradation and the prevalence of erosion in front of the river mouth. These changes, which engendered a threefold increase of the Si (0.37 at present), are reflected by the recent (1930s-present) river mouth dynamics, characterized by cessation of its long-term seaward expansion in favor of downdrift migration. This is indicative of the transition of the Sf. Gheorghe mouth from an asymmetric to a deflected wave-influenced delta morphology whose current developments mark a significant change in the multicentennial cyclic evolutionary pattern. The asymmetric to deflected transition reflects the net increase in the influence of wave-driven sediment circulation on river mouth morphology, corresponding to a critical Si threshold of ca. 0.2 (≤ 0.2: asymmetric; > 0.2: deflected).

  5. Inhibition of allergic airway inflammation by antisense-induced blockade of STAT6 expression

    Institute of Scientific and Technical Information of China (English)

    TIAN Xin-rui; TIAN Xin-li; BO Jian-ping; LI Shao-gang; LIU Zhuo-la; NIU Bo

    2011-01-01

    Background The signal transducer and activator of transcription 6 (STAT6) expression in lung epithelial cells plays a pivotal role in asthma pathogenesis. Activation of STAT6 expression results in T helper cell type 2 (Th2) cell differentiation leading to Th2-mediated IgE production, development of allergic airway inflammation and hyperreactivity. Therefore,antagonizing the expression and/or the function of STAT6 could be used as a mode of therapy for allergic airway inflammation.Methods In this study, we synthesized a 20-mer phosphorothioate antisense oligonucleotide (ASODN) overlapping the translation starting site of STAT6 and constructed STAT6 antisense RNA (pANTI-STAT6), then transfected them into murine spleen lymphocytes and analyzed the effects of antagonizing STAT6 function in vitro and in a murine model of asthma.Results In vitro, we showed suppression of STAT6 expression and interleukin (IL)-4 production of lymphocytes by STAT6 ASODN. This effect was more prominent when cells were cultured with pANTI-STAT6. In a murine model of asthma associated with allergic pulmonary inflammation in ovalbumin (OVA)-sensitized mice, local intranasal administration of fluorescein isothiocyanate (FITC)-labeled STAT6 ASODN to DNA uptake in lung cells was accompanied by a reduction of intracellular STAT6 expression. Such intrapulmonary blockade of STAT6 expression abrogated signs of lung inflammation, infiltration of eosinophils and Th2 cytokine production.Conclusion These data suggest a critical role of STAT6 in the pathogenesis of asthma and the use of local delivery of STAT6 ASODN as a novel approach for the treatment of allergic airway inflammation such as in asthma.

  6. Long term follow up of patients treated for Helicobacter pylori infection

    OpenAIRE

    Mera, R; Fontham, E T H; L. E. Bravo; Bravo, J C; Piazuelo, M B; Camargo, M. C.; Correa, P.

    2005-01-01

    Background: Helicobacter pylori infection induces progressive inflammatory changes in the gastric mucosa that may lead to gastric cancer. Understanding long term effects resulting from the cure of this infection is needed to design cancer prevention strategies.

  7. Long-Term Immunity to Lethal Acute or Chronic Type II Toxoplasma gondii Infection Is Effectively Induced in Genetically Susceptible C57BL/6 Mice by Immunization with an Attenuated Type I Vaccine Strain▿

    OpenAIRE

    Gigley, Jason P.; Fox, Barbara A.; Bzik, David J.

    2009-01-01

    C57BL/6 (B6) mice are genetically highly susceptible to chronic type II Toxoplasma gondii infections that invariably cause lethal toxoplasmic encephalitis. We examined the ability of an attenuated type I vaccine strain to elicit long-term immunity to lethal acute or chronic type II infections in susceptible B6 mice. Mice immunized with the type I cps1-1 vaccine strain were not susceptible to a lethal (100-cyst) challenge with the type II strain ME49. Immunized mice challenged with 10 ME49 cys...

  8. Long term performance of radon mitigation systems

    International Nuclear Information System (INIS)

    Researchers installed radon mitigation systems in 12 houses in Spokane, Washington and Coeur d'Alene, Idaho during the heating season 1985--1986 and continued to monitor indoor radon quarterly and annually for ten years. The mitigation systems included active sub-slab ventilation, basement over-pressurization, and crawlspace isolation and ventilation. The occupants reported various operational problems with these early mitigation systems. The long-term radon measurements were essential to track the effectiveness of the mitigation systems over time. All 12 homes were visited during the second year of the study, while a second set 5 homes was visited during the fifth year to determine the cause(s) of increased radon in the homes. During these visits, the mitigation systems were inspected and measurements of system performance were made. Maintenance and modifications were performed to improve system performance in these homes

  9. A long-term programme for IAEA

    International Nuclear Information System (INIS)

    At its fifth regular session in 1961, the IAEA General Conference adopted a resolution calling for the preparation of a long-term programme for the Agency's activities. The programme, which was prepared after extensive consultations with experts from many Member States and is intended to serve as a guide in planning and carrying out the Agency's work from 1965, has been presented to the seventh session of the General Conference by the Board of Governors and the Director General. It envisages that the Agency's main role during the next few years will be, on the one hand, to assist in preparing Member States for the introduction of atomic energy in its various peaceful uses, especially in the production of power, and, on the other, to stimulate and co-ordinate scientific and technological development with a view to making the advantages of peaceful atomic applications available to the maximum number of countries in the shortest possible time

  10. Estimating long-term health effects

    International Nuclear Information System (INIS)

    The long-term health effects from iodine 131 and cesium 137 as a result of the accident at Chernobyl Nuclear Power Plant in the USSR are discussed. Computer-generated radiation exposure distributions to the population in Europe have resulted in the following estimates: 2000-40,000 thyroid tumor cases from iodine 131 inhalation of which a few percent might be fatal; 10,000-250,000 potential thyroid tumor cases from iodine 131 absorbed via the grass-cow-milk route in the absence of actions by the public health authorities to block this exposure route; 3500-70,000 cancer cases from whole-body doses of cesium 137 (external and internal), of which approximately half might be fatal. Although there are uncertainties in these estimates they serve to indicate the magnitude of the problem

  11. Long-term variations of solar activity

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Using the Lomb-Scargle periodogram we analyzed two sunspot series: the one over the past 11000 years at the 10-year interval based upon the survey data of 14C concentration in tree-rings, reconstructed by Solanki et al.; and the sunspot number over the past 7000 years, derived from geomagnetic variations by Usoskin et al. We found the periods and quasi-periods in solar activity, such as about 225, 352, 441, 522 and 561 a, and near 1000 and 2000 a. An approach of wavelet transform was applied to check the two sunspot time series, with emphasis on investigating time-varying characteristics in the long-term fluctuations of solar activity. The results show that the lengths and amplitudes of the periods have changed with time, and large variations have taken place during some periods.

  12. Long-Term Stability of Horseshoe Orbits

    CERN Document Server

    Ćuk, Matija; Holman, Matthew J

    2012-01-01

    Unlike Trojans, horseshoe coorbitals are not generally considered to be long-term stable (Dermott and Murray, 1981; Murray and Dermott, 1999). As the lifetime of Earth's and Venus's horseshoe coorbitals is expected to be about a Gyr, we investigated the possible contribution of late-escaping inner planet coorbitals to the lunar Late Heavy Bombardment. Contrary to analytical estimates, we do not find many horseshoe objects escaping after first 100 Myr. In order to understand this behaviour, we ran a second set of simulations featuring idealized planets on circular orbits with a range of masses. We find that horseshoe coorbitals are generally long lived (and potentially stable) for systems with primary-to-secondary mass ratios larger than about 1200. This is consistent with results of Laughlin and Chambers (2002) for equal-mass pairs or coorbital planets and the instability of Jupiter's horseshoe companions (Stacey and Connors, 2008). Horseshoe orbits at smaller mass ratios are unstable because they must approa...

  13. Long-term reductions in tinnitus severity

    Directory of Open Access Journals (Sweden)

    Folmer Robert L

    2002-09-01

    Full Text Available Abstract Background This study was undertaken to assess long-term changes in tinnitus severity exhibited by patients who completed a comprehensive tinnitus management program; to identify factors that contributed to changes in tinnitus severity within this population; to contribute to the development and refinement of effective assessment and management procedures for tinnitus. Methods Detailed questionnaires were mailed to 300 consecutive patients prior to their initial appointment at the Oregon Health & Science University Tinnitus Clinic. All patients were then evaluated and treated within a comprehensive tinnitus management program. Follow-up questionnaires were mailed to the same 300 patients 6 to 36 months after their initial tinnitus clinic appointment. Results One hundred ninety patients (133 males, 57 females; mean age 57 years returned follow-up questionnaires 6 to 36 months (mean = 22 months after their initial tinnitus clinic appointment. This group of patients exhibited significant long-term reductions in self-rated tinnitus loudness, Tinnitus Severity Index scores, tinnitus-related anxiety and prevalence of current depression. Patients who improved their sleep patterns or Beck Depression Inventory scores exhibited greater reductions of tinnitus severity scores than patients who continued to experience insomnia and depression at follow-up. Conclusions Individualized tinnitus management programs that were designed for each patient contributed to overall reductions in tinnitus severity exhibited on follow-up questionnaires. Identification and treatment of patients experiencing anxiety, insomnia or depression are vital components of an effective tinnitus management program. Utilization of acoustic therapy also contributed to improvements exhibited by these patients.

  14. Long term radiological impact of thorium extraction

    International Nuclear Information System (INIS)

    Thorium extraction produces a certain amount of radioactive wastes. Potential long term radiological impact of these residues has been calculated using the recent ICRP-68 ingestion dose factors in connection with the computing code DECAY, developed at Orsay and described in this work. This code solves the well known Bateman's equations which govern the time dependence of a set of coupled radioactive nuclei. Monazites will be very likely the minerals to be exploited first, in case of an extensive use of thorium as nuclear fuel. Because monazites contain uranium as well, mining residues will contain not only the descendants of 232Th and a certain proportion of non-extracted thorium (taken here to be 5%), but also this uranium, if left in the wastes for economical reasons. If no uranium would be present at all in the mineral, the potential radiotoxicity would strongly decrease in approximately 60 years, at the pace of the 5.8 years period of 228Ra, which becomes the longest-lived radionuclide of the 4n radioactive family in the residues. Moreover, there is no risk due to radon exhalation, because of the very short period of 220Rn. These significant differences between uranium and thorium mining have to be considered in view of some estimated long term real radiological impacts due to uranium residues, which could reach a value of the order of 1 mSv/year, the dose limit recommended for the public by the recent ICRP-60. (authors). 15 refs., 4 figs., 3 tabs., 43 appendices

  15. Managing Records for the Long Term - 12363

    International Nuclear Information System (INIS)

    The U.S. Department of Energy (DOE) is responsible for managing vast amounts of information documenting historical and current operations. This information is critical to the operations of the DOE Office of Legacy Management. Managing legacy records and information is challenging in terms of accessibility and changing technology. The Office of Legacy Management is meeting these challenges by making records and information management an organizational priority. The Office of Legacy Management mission is to manage DOE post-closure responsibilities at former Cold War weapons sites to ensure the future protection of human health and the environment. These responsibilities include environmental stewardship and long-term preservation and management of operational and environmental cleanup records associated with each site. A primary organizational goal for the Office of Legacy Management is to 'Preserve, Protect, and Share Records and Information'. Managing records for long-term preservation is an important responsibility. Adequate and dedicated resources and management support are required to perform this responsibility successfully. Records tell the story of an organization and may be required to defend an organization in court, provide historical information, identify lessons learned, or provide valuable information for researchers. Loss of records or the inability to retrieve records because of poor records management processes can have serious consequences and even lead to an organisation's downfall. Organizations must invest time and resources to establish a good records management program because of its significance to the organization as a whole. The Office of Legacy Management will continue to research and apply innovative ways of doing business to ensure that the organization stays at the forefront of effective records and information management. DOE is committed to preserving records that document our nation's Cold War legacy, and the Office of Legacy

  16. Biochemical effects on long-term frozen human costal cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Santin, Stefany P.; Martinho Junior, Antonio C.; Yoshito, Daniele; Soares, Fernando A.N.; Mathor, Monica B., E-mail: mathor@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Currently, the progresses on treatment of musculoskeletal diseases with the evolving of artificial implants and the success of tissue transplantation between genetically different individuals have conducted to an increase in radiosterilization. Regarding to tissue transplantation, it is essential to have sterile tissue and many tissue banks use radiosterilization as an effective method to sterilize these tissues. However, high doses of ionizing radiation and the preservation method may induce structural modifications in the tissues, as degradation of structural scaffold, decreasing its mechanical properties. Particularly, cartilage have been preserved in high concentrations of glycerol or deep-frozen at -70 degree C for storage after radiosterilization. Therefore, it is important to study the modifications induced in cartilage by preservation methods and by radiosterilization to determine the appropriated parameters for high quality of human allografts. Costal cartilages were obtained from cadaveric donors and were frozen at -20 degree C for 2 years long in order to compare with previous studies for fresh, deep-frozen and glycerolised cartilages. The mechanical tests were carried out in a universal testing machine until sample failure. According our results, there is no significant statistical difference between stress at break of fresh, long-term - 20 degree C frozen cartilages and deep-frozen cartilage. This early result suggests, regarding to tensile property, that long-term - 20 degree C frozen cartilages corresponds to glycerolised costal cartilages irradiated with 25 kGy or deep-frozen cartilages irradiated with 25 and 50 kGy. Thus, this long-term frozen cartilages may be used for tissue banks, but more studies about effects of ionizing radiation are necessary. (author)

  17. Biochemical effects on long-term frozen human costal cartilage

    International Nuclear Information System (INIS)

    Currently, the progresses on treatment of musculoskeletal diseases with the evolving of artificial implants and the success of tissue transplantation between genetically different individuals have conducted to an increase in radiosterilization. Regarding to tissue transplantation, it is essential to have sterile tissue and many tissue banks use radiosterilization as an effective method to sterilize these tissues. However, high doses of ionizing radiation and the preservation method may induce structural modifications in the tissues, as degradation of structural scaffold, decreasing its mechanical properties. Particularly, cartilage have been preserved in high concentrations of glycerol or deep-frozen at -70 degree C for storage after radiosterilization. Therefore, it is important to study the modifications induced in cartilage by preservation methods and by radiosterilization to determine the appropriated parameters for high quality of human allografts. Costal cartilages were obtained from cadaveric donors and were frozen at -20 degree C for 2 years long in order to compare with previous studies for fresh, deep-frozen and glycerolised cartilages. The mechanical tests were carried out in a universal testing machine until sample failure. According our results, there is no significant statistical difference between stress at break of fresh, long-term - 20 degree C frozen cartilages and deep-frozen cartilage. This early result suggests, regarding to tensile property, that long-term - 20 degree C frozen cartilages corresponds to glycerolised costal cartilages irradiated with 25 kGy or deep-frozen cartilages irradiated with 25 and 50 kGy. Thus, this long-term frozen cartilages may be used for tissue banks, but more studies about effects of ionizing radiation are necessary. (author)

  18. Propofol effects on cerebellar long-term depression.

    Science.gov (United States)

    Lee, Kwan Young; Kim, Young Im; Kim, Se Hoon; Park, Hyung Seo; Park, Youn Joon; Ha, Myung Sook; Jin, Yunju; Kim, Dong Kwan

    2015-11-16

    Propofol is an intravenously administered anesthetic that induces γ-aminobutyric acid-mediated inhibition in the central nervous system. It has been implicated in prolonged movement disorders. Since the cerebellum is important for motor coordination and learning, we investigated the potential effects of propofol on cerebellar circuitry. Using the whole-cell patch-clamp technique in Wister rat cerebellar slices, we demonstrated that propofol administration impaired long-term depression from the parallel fiber (PF) to Purkinje cell (PC) synapses (PF-LTD). Also, propofol reduced metabotropic glutamate receptor 1 (mGluR1)-mediated and group I mGluR agonist-induced slow currents in PCs. These results suggest that the propofol-induced PF-LTD impairment may be related to an alteration in mGluR1 signaling, which is essential to motor learning. PMID:26455962

  19. Effect of serotonin transporter blockade on L-DOPA-induced dyskinesia in animal models of Parkinson's disease.

    Science.gov (United States)

    Fidalgo, C; Ko, W K D; Tronci, E; Li, Q; Stancampiano, R; Chuan, Q; Bezard, E; Carta, M

    2015-07-01

    Serotonin transporter blockade with selective serotonin reuptake inhibitors (SSRIs) was recently shown to counteract L-DOPA-induced dyskinesia in 6-hydroxydopamine (6-OHDA)-lesioned rats. However, this effect has never been described in Parkinson's disease (PD) patients, despite that they often receive SSRIs for the treatment of depression. In the present study, we investigated the efficacy of the SSRI citalopram against dyskinesia in two experimental models of PD, the 6-OHDA-lesioned rat and 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-treated macaque. First, we studied the acute and chronic effect of citalopram, given at different time points before L-DOPA, in L-DOPA-primed parkinsonian rats. Moreover, the acute effect of citalopram was also evaluated in dyskinetic MPTP-treated macaques. In L-DOPA-primed rats, a significant and long-lasting reduction of L-DOPA-induced dyskinesia (LID) was observed only when citalopram was given 30 min before L-DOPA, suggesting that the time of injection relative to L-DOPA is a key factor for the efficacy of the treatment. Interestingly, an acute challenge with the 5-HT1A/1B receptor agonist eltoprazine, given at the end of the chronic study, was equally effective in reducing LID in rats previously chronically treated with L-DOPA or L-DOPA plus citalopram, suggesting that no auto-receptor desensitization was induced by chronic citalopram treatment. In MPTP-treated macaques, citalopram produced a striking suppression of LID but at the expense of L-DOPA therapeutic efficacy, which represents a concern for possible clinical application. PMID:25907446

  20. Robotics for Long-Term Monitoring

    International Nuclear Information System (INIS)

    While long-term monitoring and stewardship means many things to many people, DOE has defined it as The physical controls, institutions, information, and other mechanisms needed to ensure protection of people and the environment at sites where DOE has completed or plans to complete cleanup (e.g., landfill closures, remedial actions, and facility stabilization). Across the United States, there are thousands of contaminated sites with multiple contaminants released from multiple sources where contaminants have transported and commingled. The U.S. government and U.S. industry are responsible for most of the contamination and are landowners of many of these contaminated properties. These sites must be surveyed periodically for various criteria including structural deterioration, water intrusion, integrity of storage containers, atmospheric conditions, and hazardous substance release. The surveys, however, are intrusive, time-consuming, and expensive and expose survey personnel to radioactive contamination. In long-term monitoring, there's a need for an automated system that will gather and report data from sensors without costly human labor. In most cases, a SCADA (Supervisory Control and Data Acquisition) unit is used to collect and report data from a remote location. A SCADA unit consists of an embedded computer with data acquisition capabilities. The unit can be configured with various sensors placed in different areas of the site to be monitored. A system of this type is static, i.e., the sensors, once placed, cannot be moved to other locations within the site. For those applications where the number of sampling locations would require too many sensors, or where exact location of future problems is unknown, a mobile sensing platform is an ideal solution. In many facilities that undergo regular inspections, the number of video cameras and air monitors required to eliminate the need for human inspections is very large and far too costly. HCET's remote harsh

  1. Melatonin Counteracts at a Transcriptional Level the Inflammatory and Apoptotic Response Secondary to Ischemic Brain Injury Induced by Middle Cerebral Artery Blockade in Aging Rats

    OpenAIRE

    Paredes, Sergio D.; Rancan, Lisa; Kireev, Roman; González, Alberto; Louzao, Pedro; González, Pablo; Rodríguez-Bobada, Cruz; García, Cruz; Vara, Elena; Tresguerres, Jesús A.F.

    2015-01-01

    Abstract Aging increases oxidative stress and inflammation. Melatonin counteracts inflammation and apoptosis. This study investigated the possible protective effect of melatonin on the inflammatory and apoptotic response secondary to ischemia induced by blockade of the right middle cerebral artery (MCA) in aging male Wistar rats. Animals were subjected to MCA obstruction. After 24 h or 7 days of procedure, 14-month-old nontreated and treated rats with a daily dose of 10 mg/kg melatonin were s...

  2. The Long-Term Outcomes of Double White Dwarf Mergers

    Science.gov (United States)

    Schwab, Josiah

    2016-01-01

    Binary star systems composed of two white dwarfs are a natural outcome of stellar evolution. Angular momentum losses from gravitational wave radiation cause the binary system's orbit to shrink until the two white dwarfs merge. The final outcome of the merger depends on the masses of the white dwarfs. Some potential outcomes, such as supernova explosions, may occur during or soon after the merger. Other outcomes, which I will refer to as "long-term" outcomes, occur as the merger remnant cools and its structure adjusts to the new state created during the energetic merger.In my dissertation, I quantitatively explore the long-term outcomes of the mergers of two white dwarfs. I focus primarily on the formation of neutron stars via accretion-induced collapse and the formation of two types of unusual stars, the single sub-dwarf B stars (hot, core helium fusing stars) and the R Coronae Borealis stars (cool, carbon-rich giant stars). Beginning with the results from my previous simulations of the short-lived viscous disk initially present in these remnants, I use the state-of-the-art MESA stellar evolution code to follow their thermal evolution.This work improves the quantitative understanding of which white dwarf binaries lead to a particular outcome and better characterizes the observational signatures of these outcomes. For systems that will undergo accretion-induced collapse, these simulations yield improved progenitor models that can then be used to explore the collapse and formation of a neutron star.

  3. Comparison of long-term care in an acute care institution and in a long-term care institution

    OpenAIRE

    Friedman, R; Kalant, N.

    1998-01-01

    BACKGROUND: Acute care hospitals in Quebec are required to reserve 10% of their beds for patients receiving long-term care while awaiting transfer to a long-term care facility. It is widely believed that this is inefficient because it is more costly to provide long-term care in an acute care hospital than in one dedicated to long-term care. The purpose of this study was to compare the quality and cost of long-term care in an acute care hospital and in a long-term care facility. METHODS: A con...

  4. Elevated rheumatoid factor and long term risk of rheumatoid arthritis

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Schnohr, Peter;

    2012-01-01

    To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis.......To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis....

  5. DIFFERENTIAL DIAGNOSIS OF LONG TERM TONGUE ULCERS

    Directory of Open Access Journals (Sweden)

    Hegde Nidarsh D.

    2012-08-01

    Full Text Available Oral ulcers is a very common disorder of the oral mucosa. Patients with signs or symptoms of oral ulcers are sometimes referred to gastroenterology clinics, however, in most instances the ulcers does not reflect gastrointestinal disease, some with a chronic non- healing ulcer are advised biopsy. Indeed, a spectrum of disorders can give rise to oral mucosal ulcers ranging from minor local trauma to significant local disease such as malignancy or systemic illness. Lesions of the tongue have a broad differential diagnosis ranging from benign idiopathic processes to infections, cancers, and infiltrative disorders. This article will focus on common ulcerative disorders of the tongue in aspects of their clinical features and differential diagnosis, two case reports with the diagnosis and conservative management for long-term chronic ulcers. The two cases which are reported in this article had a differential diagnosis of Squamous cell carcinoma of the tongue. The clinical picture was craterlike lesion, having a velvety-red base and a rolled, indurated border and most important painless in both cases. Removal of the irritant which was the tooth, rehabilitation of the oral mucosa by lubrication with Cocus Nucifera resulted in the healing of the ulcers. Functional components of Cocus Nucifera are Squaline, tocopherol, phytosterols and other sterols which are all plant steroids.

  6. Long-term corrosion testing pan.

    Energy Technology Data Exchange (ETDEWEB)

    Wall, Frederick Douglas; Brown, Neil R. (Los Alamos National Laboratory, Los Alamos, NM)

    2008-08-01

    This document describes the testing and facility requirements to support the Yucca Mountain Project long-term corrosion testing needs. The purpose of this document is to describe a corrosion testing program that will (a) reduce model uncertainty and variability, (b) reduce the reliance upon overly conservative assumptions, and (c) improve model defensibility. Test matrices were developed for 17 topical areas (tasks): each matrix corresponds to a specific test activity that is a subset of the total work performed in a task. A future document will identify which of these activities are considered to be performance confirmation activities. Detailed matrices are provided for FY08, FY09 and FY10 and rough order estimates are provided for FY11-17. Criteria for the selection of appropriate test facilities were developed through a meeting of Lead Lab and DOE personnel on October 16-17, 2007. These criteria were applied to the testing activities and recommendations were made for the facility types appropriate to carry out each activity. The facility requirements for each activity were assessed and activities were identified that can not be performed with currently available facilities. Based on this assessment, a total of approximately 10,000 square feet of facility space is recommended to meet all future testing needs, given that all testing is consolidated to a single location. This report is a revision to SAND2007-7027 to address DOE comments and add a series of tests to address NWTRB recommendations.

  7. Long-term corrosion testing plan.

    Energy Technology Data Exchange (ETDEWEB)

    Wall, Frederick Douglas; Brown, Neil R. (Los Alamos National Laboratory, Los Alamos, NM)

    2009-02-01

    This document describes the testing and facility requirements to support the Yucca Mountain Project long-term corrosion testing program. The purpose of this document is to describe a corrosion testing program that will (a) reduce model uncertainty and variability, (b) reduce the reliance upon overly conservative assumptions, and (c) improve model defensibility. Test matrices were developed for 17 topical areas (tasks): each matrix corresponds to a specific test activity that is a subset of the total work performed in a task. A future document will identify which of these activities are considered to be performance confirmation activities. Detailed matrices are provided for FY08, FY09 and FY10 and rough order estimates are provided for FY11-17. Criteria for the selection of appropriate test facilities were developed through a meeting of Lead Lab and DOE personnel on October 16-17, 2007. These criteria were applied to the testing activities and recommendations were made for the facility types appropriate to carry out each activity. The facility requirements for each activity were assessed and activities were identified that can not be performed with currently available facilities. Based on this assessment, a total of approximately 10,000 square feet of facility space is recommended to accommodate all future testing, given that all testing is consolidated to a single location. This report is a revision to SAND2008-4922 to address DOE comments.

  8. Long-Term Soft Denture Lining Materials

    Directory of Open Access Journals (Sweden)

    Grzegorz Chladek

    2014-08-01

    Full Text Available Long-term soft denture lining (LTSDL materials are used to alleviate the trauma associated with wearing complete dentures. Despite their established clinical efficacy, the use of LTSDLs has been limited due to the unfavorable effects of the oral environment on some of their mechanical and performance characteristics. The unresolved issue of LTSDL colonization by Candida albicans is particularly problematic. Silicone-based LTSDL (SLTSDL materials, which are characterized by more stable hardness, sorption and solubility than acrylic-based LTSDLs (ALTSDLs, are currently the most commonly used LTSDLs. However, SLTSDLs are more prone to debonding from the denture base. Moreover, due to their limitations, the available methods for determining bond strength do not fully reflect the actual stability of these materials under clinical conditions. SLTSDL materials exhibit favorable viscoelastic properties compared with ALTSDLs. Furthermore, all of the lining materials exhibit an aging solution-specific tendency toward discoloration, and the available cleansers are not fully effective and can alter the mechanical properties of LTSDLs. Future studies are needed to improve the microbiological resistance of LTSDLs, as well as some of their performance characteristics.

  9. Long-term corrosion testing plan

    International Nuclear Information System (INIS)

    This document describes the testing and facility requirements to support the Yucca Mountain Project long-term corrosion testing program. The purpose of this document is to describe a corrosion testing program that will (a) reduce model uncertainty and variability, (b) reduce the reliance upon overly conservative assumptions, and (c) improve model defensibility. Test matrices were developed for 17 topical areas (tasks): each matrix corresponds to a specific test activity that is a subset of the total work performed in a task. A future document will identify which of these activities are considered to be performance confirmation activities. Detailed matrices are provided for FY08, FY09 and FY10 and rough order estimates are provided for FY11-17. Criteria for the selection of appropriate test facilities were developed through a meeting of Lead Lab and DOE personnel on October 16-17, 2007. These criteria were applied to the testing activities and recommendations were made for the facility types appropriate to carry out each activity. The facility requirements for each activity were assessed and activities were identified that can not be performed with currently available facilities. Based on this assessment, a total of approximately 10,000 square feet of facility space is recommended to accommodate all future testing, given that all testing is consolidated to a single location. This report is a revision to SAND2008-4922 to address DOE comments.

  10. Long-term corrosion testing pan

    International Nuclear Information System (INIS)

    This document describes the testing and facility requirements to support the Yucca Mountain Project long-term corrosion testing needs. The purpose of this document is to describe a corrosion testing program that will (a) reduce model uncertainty and variability, (b) reduce the reliance upon overly conservative assumptions, and (c) improve model defensibility. Test matrices were developed for 17 topical areas (tasks): each matrix corresponds to a specific test activity that is a subset of the total work performed in a task. A future document will identify which of these activities are considered to be performance confirmation activities. Detailed matrices are provided for FY08, FY09 and FY10 and rough order estimates are provided for FY11-17. Criteria for the selection of appropriate test facilities were developed through a meeting of Lead Lab and DOE personnel on October 16-17, 2007. These criteria were applied to the testing activities and recommendations were made for the facility types appropriate to carry out each activity. The facility requirements for each activity were assessed and activities were identified that can not be performed with currently available facilities. Based on this assessment, a total of approximately 10,000 square feet of facility space is recommended to meet all future testing needs, given that all testing is consolidated to a single location. This report is a revision to SAND2007-7027 to address DOE comments and add a series of tests to address NWTRB recommendations

  11. Long term results of mandibular distraction

    Directory of Open Access Journals (Sweden)

    Batra Puneet

    2006-03-01

    Full Text Available Mandibular distraction osteogenesis has become a popular surgical modality due to its many advantages over conventional orthognathic surgical procedures. However, in spite of the technique having been used for over 15 years, no concrete long term results are available regarding the stability of results. We discuss the various studies which have reported either in favour or against the stablility of results after distraction. We report a series of 6 cases (3 unilateral and 3 bilateral distraction where distraction was carried out before puberty and followed them up to seven years after removal of distractors. This case series shows that results achieved by distraction osteogenesis are unstable or best unpredictable with respect to producing a permanent size increase in the mandible. The role of the distraction osteogenesis in overcoming the pterygomassetric sling is questionable. We suggest a multicenter study with adequate patient numbers treated with a similar protocol and documented after growth cessation to have meaningful conclusions on the debate of distraction osteogenesis versus orthognathic surgery.

  12. CERN Services for Long Term Data Preservation

    CERN Document Server

    Shiers, Jamie; Blomer, Jakob; Ganis, Gerardo; Dallmeier-Tiessen, Sunje; Simko, Tibor; Cancio Melia, German; CERN. Geneva. IT Department

    2016-01-01

    In this paper we describe the services that are offered by CERN for Long Term preservation of High Energy Physics (HEP) data, with the Large Hadron Collider (LHC) as a key use case. Data preservation is a strategic goal for European High Energy Physics (HEP), as well as for the HEP community worldwide and we position our work in this global content. Specifically, we target the preservation of the scientific data, together with the software, documentation and computing environment needed to process, (re-)analyse or otherwise (re-)use the data. The target data volumes range from hundreds of petabytes (PB – 10^15 bytes) to hundreds of exabytes (EB – 10^18 bytes) for a target duration of several decades. The Use Cases driving data preservation are presented together with metrics that allow us to measure how close we are to meeting our goals, including the possibility for formal certification for at least part of this work. Almost all of the services that we describe are fully generic – the exception being A...

  13. Long term results of Wilms' tumor

    International Nuclear Information System (INIS)

    Sixteen long term survivors of Wilms' tumor which were experienced in our deprtment were analyzed. No patients showed abnormalities in non-specific cell mediated immunity, endocrine function, secondary sexual development or renal function. In patients who were followed more than 10 years after surgery, the function of the remaining kidney, as determined by DMSA uptake, was well developed. In 15 patients who were treated by radiotherapy, changes in the spinal bodies were seen in all 15, scoliosis (average 9 deg) in 14 and hypoplasia in the iliac bone on the irradiated side in 12. In 14 patients who were examined by CT scan, atrophies of the erector spinae and illopsoas muscles on the irradiated side were seen in all cases. A significant correlation between the severity of the atrophic erector spinae muscle and the degree of scoliosis was obtained. Sixty nine patients with Wilms' tumor who survived more than ten years after surgery were found in the files of 13 institutions in our conutry. Our of them, 25 (36%) developed late disturbances and many of them were due to irradiation therapy. (author)

  14. Long term prospects for world gas trade

    International Nuclear Information System (INIS)

    Results are presented from a world gas trade model used to forecast long term gas markets. Assumptions that went into the model are described, including the extent of current proven gas reserves, production ratios, total energy and gas demand, gas supply cost curves for each producing country, available gas liquefaction and transportation facilities, and liquefied natural gas (LNG) shipping costs. The results indicate that even with generally very low supply costs for most gas producing basins, gas trade will continue to be restricted by the relatively high cost of transportation, whether by pipeline or tanker. As a consequence, future gas trade will tend to be regionally oriented. United States gas imports will come mostly from Canada, Venezuela, and Mexico; Western Europe will largely be supplied by the Soviet Union and Africa, and Japan's requirements will generally be met by Pacific Rim producers. Although the Middle East has vast quantities of gas reserves, its export growth will continue to be hampered by its remote location from major markets. 16 figs

  15. Long-term predictions using natural analogues

    Energy Technology Data Exchange (ETDEWEB)

    Ewing, R.C. [Univ. of New Mexico, Albuquerque, NM (United States)

    1995-09-01

    One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10{sup 3}-10{sup 5} years) required by regulatory agencies for performance assessment. The direct validation of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems (e.g., {open_quotes}natural analogues{close_quotes}) provide perhaps the only means of partial {open_quotes}validation,{close_quotes} as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (nm to km) and temporal (10{sup 3}-10{sup 8} years) scales and in highly complex terranes in which unknown synergisms may affect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the {open_quotes}validation{close_quotes} of performance assessments.

  16. Allogeneic radiation chimeras: long-term studies

    International Nuclear Information System (INIS)

    Lethally irradiated mice protected with allogeneic fetal liver cells or with syngeneic or allogeneic marrow and spleen cells treated with antisera to mouse immunoglobulins or to the T cell-associated 0 antigen and their controls were observed for up to 750 days. The best survival rates were found in the large groups given syngeneic marrow and spleen or allogeneic fetal liver cells (70-85 percent 700-day survival); in contrast, 43 percent of the group injected with allogeneic cells treated with anti-0 serum and 19 percent of those given antimmunoglobulin-treated cells were alive 700 days postradiation. Pulmonary infection was the most frequent cause of death of long-term survivors in all groups. Tumor incidence was increased in recipients of allogeneic cells (13 percent versus 4 percent among syngeneic chimeras), but the renal pathology seen in these groups was no greater than that noted in the syngeneic controls. Beginning 600 days after irradiation, mice from experimental and control groups were killed and their spleens were cultured with thymus-dependent antigens and the mitogens concanavalin Λ and lipopolysaccharide, Escherichia coli. The most frequent finding in all groups was mild to moderate impairment of T cell-dependent responses. (U.S.)

  17. Effective long term operation for Dukovany NPP

    International Nuclear Information System (INIS)

    Dukovany NPP now started third decade of service that is also its last decade of design life time. It is clear that the NPP has all considerations for service past the design life time called Long Term Operation (LTO). This LTO has two main aspects, technical and economical, that influence each other. From technical view the age of NPP systems, structures and components (SSCs) affects negatively the ability to perform necessary design changes in a good quality and also the long lived SSC reliability. These possible impacts have also their safety aspects and to obtain regulatory body agreement with LTO of NPP it is necessary to show that these impacts are acceptable. It means to show that all applied design changes are done in agreement with NPP design bases (DB) and all ageing impacts on SSCs functions important for safety are properly managed. From economical view that is significant for NPP owner it is necessary to demonstrate a required profitability of investment for effective LTO. These are reasons why Dukovany NPP performs three following projects: - Safety design bases collation and reconstitution, - Enhancement of plant life management program (New program preparation), - Technical-economical (TE) study of NPP LTO. All of these projects are managed by Nuclear Research Institute Rez plc (NRI) and performed in close cooperation with NPP staff and different co-operaters. This presentation will be concentrated to the last named project.

  18. Downlink Scheduling in Long Term Evolution

    Directory of Open Access Journals (Sweden)

    Anwar Hossain

    2015-06-01

    Full Text Available This is an investigated research article on resource block scheduling of Long Term Evolution (LTE. LTE is one of the evolutions of the Universal Mobile Telecommunication System (UMTS. It provides internet access to mobile users through smart phone, laptop and other android devices. LTE offers a high speed data and multimedia services. It supports data rates up to 100 Mbps in the downlink and 50 Mbps in the uplink transmission. Our research investigation was aim to the downlink scheduling. We have considered The Best CQI scheduling algorithm and the Round Robin scheduling algorithm. The implementation, analysis and comparison of these scheduling algorithms have been performed through MATLAB simulator. We have analyzed the impact of the scheduling schemes on the throughput and the fairness of both scheduling schemes. Here we have proposed a new scheduling algorithm that achieves a compromise between the throughput and the fairness. Orthogonal Frequency Division Multiplexing (OFDM has been adopted as the downlink transmission scheme. We have considered the impact of the channel delay on the throughput. In addition, MIMO transceiver systems have been implemented to increase the throughput

  19. The long term macroeconomic role for energy

    International Nuclear Information System (INIS)

    Arguments about the role of energy in economic systems are incomplete without analysis of the effects of changes in the price of energy. It may be true (because energy can substitute for so many other things) that we can continue to increase energy output per capita as long as we are prepared to increase energy consumption per unit of output, but if the price of energy is higher than consumers are prepared to pay the process will come to a stop. It follows that the output at any point in time is the result of an equilibrium between a great many factors in the economy one of which is the price of energy. The question that I now pose is whether the price of energy is an especially important factor. The subject is analyzed under the headings: the economics of energy price; a first attempt to model long-term effects; what is a price hike; modelling energy price hikes; implications and lessons for nuclear energy; the present reality. (author)

  20. BK K+ channel blockade inhibits radiation-induced migration/brain infiltration of glioblastoma cells.

    Science.gov (United States)

    Edalat, Lena; Stegen, Benjamin; Klumpp, Lukas; Haehl, Erik; Schilbach, Karin; Lukowski, Robert; Kühnle, Matthias; Bernhardt, Günther; Buschauer, Armin; Zips, Daniel; Ruth, Peter; Huber, Stephan M

    2016-03-22

    Infiltration of the brain by glioblastoma cells reportedly requires Ca2+ signals and BK K+ channels that program and drive glioblastoma cell migration, respectively. Ionizing radiation (IR) has been shown to induce expression of the chemokine SDF-1, to alter the Ca2+ signaling, and to stimulate cell migration of glioblastoma cells. Here, we quantified fractionated IR-induced migration/brain infiltration of human glioblastoma cells in vitro and in an orthotopic mouse model and analyzed the role of SDF-1/CXCR4 signaling and BK channels. To this end, the radiation-induced migratory phenotypes of human T98G and far-red fluorescent U-87MG-Katushka glioblastoma cells were characterized by mRNA and protein expression, fura-2 Ca2+ imaging, BK patch-clamp recording and transfilter migration assay. In addition, U-87MG-Katushka cells were grown to solid glioblastomas in the right hemispheres of immunocompromised mice, fractionated irradiated (6 MV photons) with 5 × 0 or 5 × 2 Gy, and SDF-1, CXCR4, and BK protein expression by the tumor as well as glioblastoma brain infiltration was analyzed in dependence on BK channel targeting by systemic paxilline application concomitant to IR. As a result, IR stimulated SDF-1 signaling and induced migration of glioblastoma cells in vitro and in vivo. Importantly, paxilline blocked IR-induced migration in vivo. Collectively, our data demonstrate that fractionated IR of glioblastoma stimulates and BK K+ channel targeting mitigates migration and brain infiltration of glioblastoma cells in vivo. This suggests that BK channel targeting might represent a novel approach to overcome radiation-induced spreading of malignant brain tumors during radiotherapy. PMID:26893360

  1. IL-1β Receptor Blockade Protects Islets Against Pro-inflammatory Cytokine Induced Necrosis and Apoptosis

    OpenAIRE

    Schwarznau, Alice; Hanson, Matthew S.; Sperger, Jamie M.; Schram, Brian R; Danobeitia, Juan S.; Greenwood, Krista K.; Vijayan, Ashwanth; Fernandez, Luis A.

    2009-01-01

    Pro-inflammatory cytokines (PIC) impair islet viability and function by activating inflammatory pathways that induce both necrosis and apoptosis. The aim of this study was to utilize an in vitro rat islet model to evaluate the efficacy of a clinically approved IL-1 receptor antagonist (Anakinra) in blocking PIC induced islet impairment. Isolated rat islets were cultured for 48h ± PIC (IL-1β, IFNγ, and TNFα and ±IL-1ra then assayed for cellular integrity by flow cytometry, MAPK phosphorylation...

  2. Blockade of LFA-1 augments in vitro differentiation of antigen-induced Foxp3+ Treg cells

    OpenAIRE

    Verhagen, Johan; Wraith, David C.

    2014-01-01

    Adoptive transfer of antigen-specific, in vitro-induced Foxp3+ Treg (iTreg) cells protects against autoimmune disease. To generate antigen-specific iTreg cells at high purity, however, remains a challenge. Whereas polyclonal T cell stimulation with anti-CD3 and anti-CD28 antibody yields Foxp3+ iTreg cells at a purity of 90–95%, antigen-induced iTreg cells typically do not exceed a purity of 65–75%, even in a TCR-transgenic model. In a similar vein to thymic Treg cell selection, iTreg cell dif...

  3. Flexibility and reliability in long-term planning exercises dedicated to the electricity sector

    Energy Technology Data Exchange (ETDEWEB)

    Maizi, Nadia; Drouineau, Mathilde; Assoumou, Edi; Mazauric, Vincent

    2010-09-15

    Long-term planning models are useful to build plausible options for future energy systems and must consequently address the technological feasibility and associated cost of these options. This paper focuses on the electricity sector and on problems of flexibility and reliability in power systems in order to improve results provided by long-term planning exercises: flexibility needs are integrated as an additional criterion for new investment decisions and, reliability requirements are assessed through the level of electrical losses they induced and a related cost. These approaches are implemented in a long-term planning model and demonstrated through a study of the Reunion Island.

  4. Brief subthreshold events can act as Hebbian signals for long-term plasticity.

    Directory of Open Access Journals (Sweden)

    Elodie Fino

    Full Text Available BACKGROUND: Action potentials are thought to be determinant for the induction of long-term synaptic plasticity, the cellular basis of learning and memory. However, neuronal activity does not lead systematically to an action potential but also, in many cases, to synaptic depolarizing subthreshold events. This is particularly exemplified in corticostriatal information processing. Indeed, the striatum integrates information from the whole cerebral cortex and, due to the membrane properties of striatal medium spiny neurons, cortical inputs do not systematically trigger an action potential but a wide range of subthreshold postsynaptic depolarizations. Accordingly, we have addressed the following question: does a brief subthreshold event act as a Hebbian signal and induce long-term synaptic efficacy changes? METHODOLOGY/PRINCIPAL FINDINGS: Here, using perforated patch-clamp recordings on rat brain corticostriatal slices, we demonstrate, that brief (30 ms subthreshold depolarizing events in quasi-coincidence with presynaptic activity can act as Hebbian signals and are sufficient to induce long-term synaptic plasticity at corticostriatal synapses. This "subthreshold-depolarization dependent plasticity" (SDDP induces strong, significant and bidirectional long-term synaptic efficacy changes at a very high occurrence (81% for time intervals between pre- and postsynaptic stimulations (Deltat of -110induce robust long-term depression (cannabinoid type-1 receptor-activation dependent as well as long-term potentiation (NMDA receptor-activation dependent. CONCLUSION/SIGNIFICANCE: Our data show the existence of a robust, reliable and timing-dependent bidirectional long-term plasticity induced by brief subthreshold events paired with presynaptic activity. The existence of a subthreshold-depolarization dependent plasticity extends considerably, beyond the action potential, the neuron's capabilities to

  5. Effect of tyrosine kinase blockade on norepinephrine-induced cytosolic calcium response in rat afferent arterioles

    DEFF Research Database (Denmark)

    Salomonsson, Max; Arendshorst, William J

    2004-01-01

    We used genistein (Gen) and tyrphostin 23 (Tyr-23) to evaluate the importance of tyrosine phosphorylation in norepinephrine (NE)-induced changes in intracellular free calcium concentration ([Ca(2+)](i)) in rat afferent arterioles. [Ca(2+)](i) was measured in microdissected arterioles using ratiom...

  6. Scientific Understanding from Long Term Observations: Insights from the Long Term Ecological Research (LTER) Program

    Science.gov (United States)

    Gosz, J.

    2001-12-01

    The network dedicated to Long Term Ecological Research (LTER) in the United States has grown to 24 sites since it was formed in 1980. Long-term research and monitoring are performed on parameters thatare basic to all ecosystems and are required to understand patterns, processes, and relationship to change. Collectively, the sites in the LTER Network provide opportunities to contrast marine, coastal, and continental regions, the full range of climatic gradients existing in North America, and aquatic and terrestrial habitats in a range of ecosystem types. The combination of common core areas and long-term research and monitoring in many habitats have allowed unprecedented abilities to understand and compare complex temporal and spatial dynamics associated with issues like climate change, effects of pollution, biodiversity and landuse. For example, McMurdo Dry Valley in the Antarctic has demonstrated an increase in glacier mass since 1993 which coincides with a period of cooler than normal summers and more than average snowfall. In contrast, the Bonanza Creek and Toolik Lake sites in Alaska have recorded a warming period unprecedented in the past 200 years. Nitrogen deposition effects have been identified through long-term watershed studies on biogeochemical cycles, especially at Coweeta Hydrological Lab, Harvard Forest, and the Hubbard Brook Experimental Forest. In aquatic systems, such as the Northern Temperate Lakes site, long-term data revealed time lags in effects of invaders and disturbance on lake communities. Biological recovery from an effect such as lake acidification was shown to lag behind chemical recovery. The long-term changes documented over 2 decades have been instrumental in influencing management practices in many of the LTER areas. In Puerto Rico, the Luquillo LTER demonstrated that dams obstruct migrations of fish and freshwater shrimp and water abstraction at low flows can completely obliterate downstream migration of juveniles and damage

  7. Long-term phenological shifts in raptor migration and climate.

    Directory of Open Access Journals (Sweden)

    Mikaël Jaffré

    Full Text Available Climate change is having a discernible effect on many biological and ecological processes. Among observed changes, modifications in bird phenology have been widely documented. However, most studies have interpreted phenological shifts as gradual biological adjustments in response to the alteration of the thermal regime. Here we analysed a long-term dataset (1980-2010 of short-distance migratory raptors in five European regions. We revealed that the responses of these birds to climate-induced changes in autumn temperatures are abrupt and synchronous at a continental scale. We found that when the temperatures increased, birds delayed their mean passage date of autumn migration. Such delay, in addition to an earlier spring migration, suggests that a significant warming may induce an extension of the breeding-area residence time of migratory raptors, which may eventually lead to residency.

  8. HLW Long-term Management Technology Development

    International Nuclear Information System (INIS)

    Permanent disposal of spent nuclear fuels from the power generation is considered to be the unique method for the conservation of human being and nature in the present and future. In spite of spent nuclear fuels produced from power generation, based on the recent trends on the gap between supply and demand of energy, the advance on energy price and reduction of carbon dioxide, nuclear energy is expected to play a role continuously in Korea. It means that a new concept of nuclear fuel cycle is needed to solve problems on spent nuclear fuels. The concept of the advanced nuclear fuel cycle including PYRO processing and SFR was presented at the 255th meeting of the Atomic Energy Commission. According to the concept of the advanced nuclear fuel cycle, actinides and long-term fissile nuclides may go out of existence in SFR. And then it is possible to dispose of short term decay wastes without a great risk bearing. Many efforts had been made to develop the KRS for the direct disposal of spent nuclear fuels in the representative geology of Korea. But in the case of the adoption of Advanced nuclear fuel cycle, the disposal of PYRO wastes should be considered. For this, we carried out the Safety Analysis on HLW Disposal Project with 5 sub-projects such as Development of HLW Disposal System, Radwaste Disposal Safety Analysis, Feasibility study on the deep repository condition, A study on the Nuclide Migration and Retardation Using Natural Barrier, and In-situ Study on the Performance of Engineered Barriers

  9. Perinatal respiratory infections and long term consequences

    Directory of Open Access Journals (Sweden)

    Luciana Indinnimeo

    2015-10-01

    Full Text Available Respiratory syncytial virus (RSV is the most important pathogen in the etiology of respiratory infections in early life. 50% of children are affected by RSV within the first year of age, and almost all children become infected within two years. Numerous retrospective and prospective studies linking RSV and chronic respiratory morbidity show that RSV bronchiolitis in infancy is followed by recurrent wheezing after the acute episod. According to some authors a greater risk of wheezing in children with a history of RSV bronchiolitis would be limited to childhood, while according to others this risk would be extended into adolescence and adulthood. To explain the relationship between RSV infection and the development of bronchial asthma or the clinical pathogenetic patterns related to a state of bronchial hyperreactivity, it has been suggested that RSV may cause alterations in the response of the immune system (immunogenic hypothesis, activating directly mast cells and basophils and changing the pattern of differentiation of immune cells present in the bronchial tree as receptors and inflammatory cytokines. It was also suggested that RSV infection can cause bronchial hyperreactivity altering nervous airway modulation, acting on nerve fibers present in the airways (neurogenic hypothesis.The benefits of passive immunoprophylaxis with palivizumab, which seems to represent an effective approach in reducing the sequelae of RSV infection in the short- and long-term period, strengthen the implementation of prevention programs with this drug, as recommended by the national guidelines of the Italian Society of Neonatology. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy · October 26th-31st, 2015 · From the womb to the adultGuest Editors: Vassilios Fanos (Cagliari, Italy, Michele Mussap (Genoa, Italy, Antonio Del Vecchio (Bari, Italy, Bo Sun (Shanghai, China, Dorret I. Boomsma (Amsterdam, the

  10. Early calcium increase triggers the formation of olfactory long-term memory in honeybees

    Directory of Open Access Journals (Sweden)

    Matsumoto Yukihisa

    2009-06-01

    Full Text Available Abstract Background Synaptic plasticity associated with an important wave of gene transcription and protein synthesis underlies long-term memory processes. Calcium (Ca2+ plays an important role in a variety of neuronal functions and indirect evidence suggests that it may be involved in synaptic plasticity and in the regulation of gene expression correlated to long-term memory formation. The aim of this study was to determine whether Ca2+ is necessary and sufficient for inducing long-term memory formation. A suitable model to address this question is the Pavlovian appetitive conditioning of the proboscis extension reflex in the honeybee Apis mellifera, in which animals learn to associate an odor with a sucrose reward. Results By modulating the intracellular Ca2+ concentration ([Ca2+]i in the brain, we show that: (i blocking [Ca2+]i increase during multiple-trial conditioning selectively impairs long-term memory performance; (ii conversely, increasing [Ca2+]i during single-trial conditioning triggers long-term memory formation; and finally, (iii as was the case for long-term memory produced by multiple-trial conditioning, enhancement of long-term memory performance induced by a [Ca2+]i increase depends on de novo protein synthesis. Conclusion Altogether our data suggest that during olfactory conditioning Ca2+ is both a necessary and a sufficient signal for the formation of protein-dependent long-term memory. Ca2+ therefore appears to act as a switch between short- and long-term storage of learned information.

  11. PD-1/CTLA-4 Blockade Inhibits Epstein-Barr Virus-Induced Lymphoma Growth in a Cord Blood Humanized-Mouse Model.

    Directory of Open Access Journals (Sweden)

    Shi-Dong Ma

    2016-05-01

    Full Text Available Epstein-Barr virus (EBV infection causes B cell lymphomas in humanized mouse models and contributes to a variety of different types of human lymphomas. T cells directed against viral antigens play a critical role in controlling EBV infection, and EBV-positive lymphomas are particularly common in immunocompromised hosts. We previously showed that EBV induces B cell lymphomas with high frequency in a cord blood-humanized mouse model in which EBV-infected human cord blood is injected intraperitoneally into NOD/LtSz-scid/IL2Rγnull (NSG mice. Since our former studies showed that it is possible for T cells to control the tumors in another NSG mouse model engrafted with both human fetal CD34+ cells and human thymus and liver, here we investigated whether monoclonal antibodies that block the T cell inhibitory receptors, PD-1 and CTLA-4, enhance the ability of cord blood T cells to control the outgrowth of EBV-induced lymphomas in the cord-blood humanized mouse model. We demonstrate that EBV-infected lymphoma cells in this model express both the PD-L1 and PD-L2 inhibitory ligands for the PD-1 receptor, and that T cells express the PD-1 and CTLA-4 receptors. Furthermore, we show that the combination of CTLA-4 and PD-1 blockade strikingly reduces the size of lymphomas induced by a lytic EBV strain (M81 in this model, and that this anti-tumor effect requires T cells. PD-1/CTLA-4 blockade markedly increases EBV-specific T cell responses, and is associated with enhanced tumor infiltration by CD4+ and CD8+ T cells. In addition, PD-1/CTLA-4 blockade decreases the number of both latently, and lytically, EBV-infected B cells. These results indicate that PD-1/CTLA-4 blockade enhances the ability of cord blood T cells to control outgrowth of EBV-induced lymphomas, and suggest that PD-1/CTLA-4 blockade might be useful for treating certain EBV-induced diseases in humans.

  12. PD-1/CTLA-4 Blockade Inhibits Epstein-Barr Virus-Induced Lymphoma Growth in a Cord Blood Humanized-Mouse Model

    Science.gov (United States)

    Ma, Shi-Dong; Xu, Xuequn; Jones, Richard; Delecluse, Henri-Jacques; Zumwalde, Nicholas A.; Sharma, Akshat; Gumperz, Jenny E.; Kenney, Shannon C.

    2016-01-01

    Epstein-Barr virus (EBV) infection causes B cell lymphomas in humanized mouse models and contributes to a variety of different types of human lymphomas. T cells directed against viral antigens play a critical role in controlling EBV infection, and EBV-positive lymphomas are particularly common in immunocompromised hosts. We previously showed that EBV induces B cell lymphomas with high frequency in a cord blood-humanized mouse model in which EBV-infected human cord blood is injected intraperitoneally into NOD/LtSz-scid/IL2Rγnull (NSG) mice. Since our former studies showed that it is possible for T cells to control the tumors in another NSG mouse model engrafted with both human fetal CD34+ cells and human thymus and liver, here we investigated whether monoclonal antibodies that block the T cell inhibitory receptors, PD-1 and CTLA-4, enhance the ability of cord blood T cells to control the outgrowth of EBV-induced lymphomas in the cord-blood humanized mouse model. We demonstrate that EBV-infected lymphoma cells in this model express both the PD-L1 and PD-L2 inhibitory ligands for the PD-1 receptor, and that T cells express the PD-1 and CTLA-4 receptors. Furthermore, we show that the combination of CTLA-4 and PD-1 blockade strikingly reduces the size of lymphomas induced by a lytic EBV strain (M81) in this model, and that this anti-tumor effect requires T cells. PD-1/CTLA-4 blockade markedly increases EBV-specific T cell responses, and is associated with enhanced tumor infiltration by CD4+ and CD8+ T cells. In addition, PD-1/CTLA-4 blockade decreases the number of both latently, and lytically, EBV-infected B cells. These results indicate that PD-1/CTLA-4 blockade enhances the ability of cord blood T cells to control outgrowth of EBV-induced lymphomas, and suggest that PD-1/CTLA-4 blockade might be useful for treating certain EBV-induced diseases in humans. PMID:27186886

  13. GRP94 Regulates Circulating Cholesterol Levels through Blockade of PCSK9-Induced LDLR Degradation

    Directory of Open Access Journals (Sweden)

    Steve Poirier

    2015-12-01

    Full Text Available Clearance of circulating low-density lipoprotein cholesterol (LDLc by hepatic LDL receptors (LDLR is central for vascular health. Secreted by hepatocytes, PCSK9 induces the degradation of LDLR, resulting in higher plasma LDLc levels. Still, it remains unknown why LDLR and PCSK9 co-exist within the secretory pathway of hepatocytes without leading to complete degradation of LDLR. Herein, we identified the ER-resident GRP94, and more precisely its client-binding C-terminal domain, as a PCSK9-LDLR inhibitory binding protein. Depletion of GRP94 did not affect calcium homeostasis, induce ER stress, nor did it alter PCSK9 processing or its secretion but greatly increased its capacity to induce LDLR degradation. Accordingly, we found that hepatocyte-specific Grp94-deficient mice have higher plasma LDLc levels correlated with ∼80% reduction in hepatic LDLR protein levels. Thus, we provide evidence that, in physiological conditions, binding of PCSK9 to GRP94 protects LDLR from degradation likely by preventing early binding of PCSK9 to LDLR within the ER.

  14. Blockade of P-selectin reduces neutrophil infiltration into the ischemia-reperfusion induced murine testis

    Directory of Open Access Journals (Sweden)

    Celebi M.

    2009-01-01

    Full Text Available Germ cell apoptosis after ischemia-reperfusion (IR of the testis is dependent on neutrophil recruitment to the testis. Intravascular adhesion molecules like the P- and E- selectins play an important role in this recruitment. The purpose of this study was to inhibit neutrophil recruitment to the IR- induced testis by using a function-blocking monoclonal anti-mouse P-selectin antibody. Adult mice were subjected to a 2 h period of testicular torsion (ischemia followed by detorsion (reperfusion. Ten minutes after the onset of reperfusion mice received either the function-blocking monoclonal P-selectin antibody (FBMAB group or the isotype-matched control antibody (IMCA group. Separate groups of mice underwent a sham operation (SO group or received 500 ng of TNFα (IF group to induce inflammation. Mice were sacrificed 24 hr after reperfusion and testiscular interstitial cells were isolated and analyzed for the presence of neutrophils by means of flow cytometry. The function-blocking monoclonal P-selectin antibody reduced neutrophil recruitment to the IR-induced testis significantly. Therefore, blocking P-selectin may be therapeutically beneficial to protect postischemic testis.

  15. Long-term experimental testing of a-silicon modules

    International Nuclear Information System (INIS)

    Long-term stability of photovoltaic module electrical performance is critically important to the economic viability of PV in large-scale energy-generation applications. Equally important is having the means to conclusively demonstrate long life to potential users; this requires proven test methods that accurately predict field performance trends. To assess the long-term stability of a-Si modules and the usefulness of existing crystalline-Si test methods a number of first generation a-Si photovoltaic modules have been acquired from leading manufacturers and subjected to a variety of accelerated and real-time outdoor aging tests. Data to date indicate that the degradation of a-Si modules involves complex dependencies that negate some of the key test correlations previously established for crystalline-Si modules. Key research priorities are highlighted including light induced effects, cell corrosion leading to increased series resistance, glass breaking strength for large modules, and the development of protective encapsulants that meet the outdoor weathering and voltage isolation required for long module life

  16. Long-term stability of polymeric integrated optical components

    Science.gov (United States)

    Kwong, Wing-Ying

    2006-02-01

    Traditionally, glass has been a suitable waveguide material and passive integrated optical circuits in glass substrates are widely used as passive components. Long-term tests of optical glass flats with a high level of internal stress revealed gradual systematic-change with time to produce inconsistent results. Since long-term stability has been the primary concern for users of specific applications, investigations of instabilities in various optical materials have been carried out via measurements and tests. From the development of the integrated optical systems' point-of-view, polymers are promising candidates that possess excellent compatibility with all other materials and their associated processes. Polymeric materials offer large refractive-index contrasts, high performance, environmental stability, simple low-cost fabrication and may be processed by unconventional forming techniques. Polymer technologies can be designed to form stress-free films, so that stress-induced losses can be eliminated. Optical polymers may also be tailored to meet specific requirements for optical waveguide devices and can be highly transparent in such a way that they are not a limiting factor in components' lifetime. In this paper, tests results and characteristics of polymeric materials shall be reviewed; different types of polymer are detail-studied and a brief analysis shall be presented. Examples of passive polymeric integrated optical components are single-mode splitters, couplers, polarizers, routers, gratings, bend waveguides, power dividers, wavelength filters and wavelength multiplexers/de-multiplexers, which may find applications in the optical communication and the telecommunication industries.

  17. The steroid-sparing effect of long-term plasmapheresis in pemphigus

    DEFF Research Database (Denmark)

    Søndergaard, Klaus; Carstens, Jan; Jørgensen, Jan;

    1995-01-01

    Glucocorticoids and immunosuppressive agents can induce remission in most patients with pemphigus, but mortality remains at 5 to 15% due to complications from these drugs. We reviewed the adjunctive effect of long-term plasmapheresis in 8 patients with pemphigus. Four cases had been resistant to ...... where cyclosporine was introduced. This first report of long-term plasmapheresis demonstrates clinical efficacy in pemphigus and a considerable steroid-sparing effect....

  18. Social environment determines the long-term effects of social defeat

    OpenAIRE

    de Jong, JG; Van Der Vegt, BJ; Buwalda, B.; KOOLHAAS, JM

    2005-01-01

    A single social defeat by a dominant conspecific induces long-term changes in several physiological and behavioral parameters in rats. These changes may represent an increased vulnerability to subsequent stress and stress-related pathology. Environmental factors, in particular possibilities for social interactions, could modulate these effects. Therefore, we assessed the influence of social environment on susceptibility for the long-term effects of social defeat. Socially housed males of an u...

  19. Hot functional test chemistry - long term experience

    Energy Technology Data Exchange (ETDEWEB)

    Vonkova, K.; Kysela, J., E-mail: von@ujv.cz [Nuclear Research Inst. Rez plc, Husinec-Rez (Czech Republic); Marcinsky, M. [ENEL-SE, NPP Mochovce, Mochovce (Slovakia); Martykan, M. [CEZ-ETE, NPP Temelin, Temelin (Czech Republic)

    2010-07-01

    Primary circuit materials undergo general corrosion in high temperature, deoxygenated, neutral or mildly alkaline solutions to form thin oxide films. These oxide layers (films) serve as protective film and mitigate the further corrosion of primary materials. Inner chromium-rich oxide layer has low cation diffusion coefficients and thus control iron and nickel transport from the metal surface to the outer layer and their dissolution into the coolant. Much less corrosion products are generated by the compact, integral and stable oxide (passivation) layer. For the latest Czech and Slovak stations commissioned (Temelin and Mochovce) a modified Hot Functional Test (HFT) chemistry was developed in the NRI Rez. Chromium rich surface layer formatted due to modified HTF chemistry ensures lower corrosion rates and radiation field formation and thus also mitigates crud formation during operation. This procedure was also designed to prepare the commissioned unit for the further proper water chemistry practise. Mochovce 1 (SK) was the first station commissioned using these recommendations in 1998. Mochovce 2 (1999) and Temelin 1 and 2 (CZ - 2000 and 2002) were subsequently commissioned using these guidelines too. The main principles of the controlled primary water chemistry applied during the hot functional tests are reviewed and importance of the water chemistry, technological and other relevant parameters is stressed regarding to the quality of the passive layer formed on the primary system surfaces. Samples from Mochovce indicated that duplex oxide layers up to 20 μm thick were produced, which were mainly magnetite substituted with nickel and chromium (e.g. 60-65% Fe, 18-28% Cr, 9-12% Ni, <1% Mn and 1-2% Si on a stainless steel primary circuit sample). Long term operation experience from both nuclear power plants are discussed in this paper. Radiation field, occupational radiation exposure and corrosion layers evolution during the first c. ten years of operation are

  20. Long term property prediction of polyethylene nanocomposites

    Science.gov (United States)

    Shaito, Ali Al-Abed

    properties of the nanocomposites was analyzed by examining tensile and creep-recovery behavior of the films at temperatures in the range of 25 to -100°C. Within the measured temperature range, the materials showed a nonlinear temperature dependent response. The time-temperature superposition principle was successfully used to predict the long term behavior of LLDPE nanocomposites.

  1. Hot functional test chemistry - long term experience

    International Nuclear Information System (INIS)

    Primary circuit materials undergo general corrosion in high temperature, deoxygenated, neutral or mildly alkaline solutions to form thin oxide films. These oxide layers (films) serve as protective film and mitigate the further corrosion of primary materials. Inner chromium-rich oxide layer has low cation diffusion coefficients and thus control iron and nickel transport from the metal surface to the outer layer and their dissolution into the coolant. Much less corrosion products are generated by the compact, integral and stable oxide (passivation) layer. For the latest Czech and Slovak stations commissioned (Temelin and Mochovce) a modified Hot Functional Test (HFT) chemistry was developed in the NRI Rez. Chromium rich surface layer formatted due to modified HTF chemistry ensures lower corrosion rates and radiation field formation and thus also mitigates crud formation during operation. This procedure was also designed to prepare the commissioned unit for the further proper water chemistry practise. Mochovce 1 (SK) was the first station commissioned using these recommendations in 1998. Mochovce 2 (1999) and Temelin 1 and 2 (CZ - 2000 and 2002) were subsequently commissioned using these guidelines too. The main principles of the controlled primary water chemistry applied during the hot functional tests are reviewed and importance of the water chemistry, technological and other relevant parameters is stressed regarding to the quality of the passive layer formed on the primary system surfaces. Samples from Mochovce indicated that duplex oxide layers up to 20 μm thick were produced, which were mainly magnetite substituted with nickel and chromium (e.g. 60-65% Fe, 18-28% Cr, 9-12% Ni, <1% Mn and 1-2% Si on a stainless steel primary circuit sample). Long term operation experience from both nuclear power plants are discussed in this paper. Radiation field, occupational radiation exposure and corrosion layers evolution during the first c. ten years of operation are

  2. Effects of tachykinin NK1 or PAF receptor blockade on the lung injury induced by scorpion venom in rats.

    Science.gov (United States)

    Matos, I M; Souza, D G; Seabra, D G; Freire-Maia, L; Teixeira, M M

    1999-07-01

    In cases of severe human scorpion envenoming, lung injury is a common finding and frequently the cause of death. In the rat, two distinct mechanisms account for oedema following the intravenous injection of the venom -- acute left ventricular failure resulting from a massive release of catecholamines and an increase in pulmonary vascular permeability. In the present work, we investigated the effects of a tachykinin NK1 receptor antagonist (CP96,345, the dihydrochloride salt of (2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)methyl)-1-az abicycol[2.2.2]octan-3-amine) and its 2 R-3 R inactive enantiomer (CP96,344) on the acute lung injury induced by the i.v. injection of Tityus serrulatus venom in rats. Lung injury was assessed by evaluating the extravasation of Evans blue dye in the bronchoalveolar lavage fluid and in the lung of venom-treated and control animals. The effects of the platelet-activating factor (PAF) receptor antagonist WEB2170 (2-methyl-1-phenylimidazol[4,5c]pyridine) were evaluated for comparison. The i.v. injection of the venom induced the extravasation of Evans blue in the bronchoalveolar lavage fluid and into the left lung. Pretreament with the tachykinin NK1 receptor antagonist CP96,345, but not CP96,344, inhibited Evans blue dye extravasation in the bronchoalveolar lavage fluid and in the lung by 96% and 86%, respectively. The PAF receptor antagonist WEB2170 inhibited the increase in vascular permeability in the bronchoalveolar lavage fluid by 60% and had no effect on the extravasation to the lung parenchyma of venom-injected animals. In addition to abrogating lung injury, pretreatment of rats with CP96,345, but not CP96,344 or WEB2170, decreased by 70% the mortality induced by the venom. This is the first study to show the relevance of the tachykinin NK1 receptor in mediating lung injury and mortality in animals injected with the neurotoxic T. serrulatus venom. Blockade of the tachykinin NK1 receptor may represent an important strategy in

  3. Blockade of Extracellular ATP Effect by Oxidized ATP Effectively Mitigated Induced Mouse Experimental Autoimmune Uveitis (EAU)

    Science.gov (United States)

    Zhao, Ronglan; Liang, Dongchun; Sun, Deming

    2016-01-01

    Various pathological conditions are accompanied by ATP release from the intracellular to the extracellular compartment. Extracellular ATP (eATP) functions as a signaling molecule by activating purinergic P2 purine receptors. The key P2 receptor involved in inflammation was identified as P2X7R. Recent studies have shown that P2X7R signaling is required to trigger the Th1/Th17 immune response, and oxidized ATP (oxATP) effectively blocks P2X7R activation. In this study we investigated the effect of oxATP on mouse experimental autoimmune uveitis (EAU). Our results demonstrated that induced EAU in B6 mice was almost completely abolished by the administration of small doses of oxATP, and the Th17 response, but not the Th1 response, was significantly weakened in the treated mice. Mechanistic studies showed that the therapeutic effects involve the functional change of a number of immune cells, including dendritic cells (DCs), T cells, and regulatory T cells. OxATP not only directly inhibits the T cell response; it also suppresses T cell activation by altering the function of DCs and Foxp3+ T cell. Our results demonstrated that inhibition of P2X7R activation effectively exempts excessive autoimmune inflammation, which may indicate a possible therapeutic use in the treatment of autoimmune diseases. PMID:27196432

  4. Chronic Renin-Angiotensin System (RAS) Blockade May Not Induce Hypotension During Anaesthesia for Bariatric Surgery.

    Science.gov (United States)

    Salvetti, Guido; Di Salvo, Claudio; Ceccarini, Giovanni; Abramo, Antonio; Fierabracci, Paola; Magno, Silvia; Piaggi, Paolo; Vitti, Paolo; Santini, Ferruccio

    2016-06-01

    The use of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) for the treatment of hypertensive obese patients is steadily increasing. Some studies have reported that the use of these drugs was associated with an increased risk of hypotensive episodes, during general anaesthesia. The number of bariatric procedures is also increasing worldwide, but there is a lack of studies investigating the hypotensive effect of renin-angiotensin system (RAS) blockers in severely obese patients during general anaesthesia for bariatric surgery. The aim of this pilot study was to evaluate hemodynamic changes induced by general anaesthesia in obese patients chronically treated with ACE-I or ARB compared to a control group not treated with antihypertensive therapy. Fourteen obese subjects (mean body mass index (BMI) 47.5 kg/m(2)) treated with ACE-I or ARB and twelve obese (mean BMI 45.7 kg/m2) controls not treated with antihypertensive therapy underwent general anaesthesia to perform laparoscopic bariatric surgery. Systolic blood pressure, diastolic blood pressure, and heart rate were monitored continuously and registered at different time points: T0 before induction, then at 2, 5, 7, 10, 15, 20, 30, 60, 90, 120, and 150 min after induction, and the last time point taken following recovery from anaesthesia. A progressive reduction of both systolic and diastolic blood pressure values was observed without significant differences between the two groups. A similar trend of heart rate values was observed. In conclusion, our pilot study suggests that RAS blockers may be continued during the perioperative period in patients undergoing bariatric surgery, without increasing the risk of hypotensive episodes. PMID:26328531

  5. Electrophysiological Correlates of Long-Term Soto Zen Meditation

    Directory of Open Access Journals (Sweden)

    Henrique Adam Pasquini

    2015-01-01

    Full Text Available This study aimed to verify the electrophysiological correlates of the changes in long-term regular meditators. We use modern techniques of high-resolution electroencephalography applied to slow potentials, power spectra, and potencies related to the events. To obtain encephalographic records, we use an assembly of 128 channels in 31 subjects (17 Soto Zen Buddhist meditators. The motivation of this study was to determine whether the induced beta power would present an increase in meditators as well as a decrease in induced theta/beta ratio in absolute and relative values. However, opposite to what we expected, no significant change was found in the beta frequency. In contrast, the main findings of the study were correlations between the frequency of weekly meditation practice and the increased theta induced relative power, increase of induced power ratio (ratio theta/beta, and increase of the ratio of induced relative powers (theta/beta ratio during our task that featured an “adapted meditation,” suggesting that the meditative state of “mindfulness” is much more related to the permittivity of “distractions” by the meditators, with a deliberate reduction of attention.

  6. Wnt Signaling Is Required for Long-Term Memory Formation

    Directory of Open Access Journals (Sweden)

    Ying Tan

    2013-09-01

    Full Text Available Wnt signaling regulates synaptic plasticity and neurogenesis in the adult nervous system, suggesting a potential role in behavioral processes. Here, we probed the requirement for Wnt signaling during olfactory memory formation in Drosophila using an inducible RNAi approach. Interfering with β-catenin expression in adult mushroom body neurons specifically impaired long-term memory (LTM without altering short-term memory. The impairment was reversible, being rescued by expression of a wild-type β-catenin transgene, and correlated with disruption of a cellular LTM trace. Inhibition of wingless, a Wnt ligand, and arrow, a Wnt coreceptor, also impaired LTM. Wingless expression in wild-type flies was transiently elevated in the brain after LTM conditioning. Thus, inhibiting three key components of the Wnt signaling pathway in adult mushroom bodies impairs LTM, indicating that this pathway mechanistically underlies this specific form of memory.

  7. Silicate Urolithiasis during Long-Term Treatment with Zonisamide

    Directory of Open Access Journals (Sweden)

    Satoru Taguchi

    2013-01-01

    Full Text Available Silicate urinary calculi are rare in humans, with an incidence of 0.2% of all urinary calculi. Most cases were related to excess ingestion of silicate, typically by taking magnesium trisilicate as an antacid for peptic ulcers over a long period of time; however, there also existed unrelated cases, whose mechanism of development remains unclear. On the other hand, zonisamide, a newer antiepileptic drug, is one of the important causing agents of iatrogenic urinary stones in patients with epilepsy. The supposed mechanism is that zonisamide induces urine alkalinization and then promotes crystallization of urine components such as calcium phosphate by inhibition of carbonate dehydratase in renal tubular epithelial cells. Here, we report a case of silicate urolithiasis during long-term treatment with zonisamide without magnesium trisilicate intake and discuss the etiology of the disease by examining the silicate concentration in his urine.

  8. Long-term Ozone monitoring from space

    Science.gov (United States)

    Ahmad, S.; Johnson, J.; Serafino, G.; McPeters, R.

    Ultraviolet Spectrometer (SBUV), are archived at the Goddard DAAC and are freely available to the public. Standard products from TOMS include daily global total ozone and effective UV reflectivity of the earth-atmosphere system. Data products from future upper atmospheric research missions, e.g., the Ozone Monitoring Instrument (OMI), the Microwave Limb Sounder (MLS), and the High Resolution Dynamics Limb Sounder (HIRDLS) aboard Aura, will also be archived at the Goddard DAAC. For ozone trend analysis, a long-term data set consisting of over twenty years of ozone measurements from space and some value added research products have been produced by the NASA Goddard Space Flight Center scientists (Atmospheric Chemistry and Dynamics Branch/ Code 916) and are made available to the research community (http://code916.gsfc.nasa.gov). Examples of some of these research products are:1) daily erythermal UV exposure -estimates of harmful UV-B radiation at the surface, 2) an index to track the global transport of ash and sulfur dioxide resulting from volcanic eruptions, 3) another index to track smoke emanating from large fires and dust plumes originating from desert regions, 4) aerosol optical depth, 5) tropospheric ozone obtained from cloud-slicing techniques, and 6) a merged total ozone data product consisting of monthly mean ozone merged from six satellite instruments. The Upper Atmospheric Data Support Team has been providing science and data support to assist users in accessing and using the upper atmospheric data products. A number of tools for data access, subsetting, reprojection and mapping of orbital (Level-2) products, visualization of global gridded (Level-3) products, and data analysis have been developed at the Goddard DAAC and are freely available to the data user (http://daac.gsfc.nasa.gov) This presentation will provide highlights of the standard and value-added ozone and ancillary products, and the data services provided by the DAAC Upper Atmosphere Data Support Team.

  9. Suppression of peripheral pain by blockade of Cav2.2 channels in nociceptors induces RANKL and impairs recovery from inflammatory arthritis

    Science.gov (United States)

    Baddack, Uta; Frahm, Silke; Antolin-Fontes, Beatriz; Grobe, Jenny; Lipp, Martin; Müller, Gerd; Ibañez-Tallon, Ines

    2015-01-01

    Objective A hallmark of rheumatoid arthritis (RA) is the chronic pain that accompanies the inflammation and joint deformation. Patients with RA rate pain relief with highest priority, however, few studies have addressed the efficacy and safety of therapies directed specifically towards pain pathways. The conotoxin MVIIA (Prialt/Ziconotide) is used in humans to alleviate persistent pain syndromes because it specifically blocks the CaV2.2 voltage-gated calcium channel, which mediates the release of neurotransmitters and proinflammatory mediators from peripheral nociceptor nerve terminals. The purpose of this study was to investigate whether block of CaV2.2 can suppress arthritic pain, and to examine the progression of induced arthritis during persistent CaV2.2 blockade. Methods Transgenic mice (Tg-MVIIA) expressing a membrane-tethered form of the ω-conotoxin MVIIA, under the control of a nociceptor-specific gene, were employed. These mice were subjected to unilateral induction of joint inflammation using the Antigen- and Collagen-Induced Arthritis (ACIA) model. Results We observed that CaV2.2-blockade mediated by t-MVIIA effectively suppressed arthritis-induced pain; however, in contrast to their wild-type littermates, which ultimately regained use of their injured joint as inflammation subsides, Tg-MVIIA mice showed continued inflammation with an up-regulation of the osteoclast activator RANKL and concomitant joint and bone destruction. Conclusion Altogether, our results indicate that alleviation of peripheral pain by blockade of CaV2.2- mediated calcium influx and signaling in nociceptor sensory neurons, impairs recovery from induced arthritis and point to the potentially devastating effects of using CaV2.2 channel blockers as analgesics during inflammation. PMID:25733371

  10. Regional blockade by neuroleptic drugs of in vivo 3H-spiperone binding in the rat brain. Relation to blockade of apomorphine induced hyperactivity and stereotypies

    International Nuclear Information System (INIS)

    The regional prevention by neuroleptic drugs of specific in vivo 3H-spiperone binding was studied in the rat brain. L-sulpiride, thioridazine and clozapine were found to reduce the 3H-spiperone bindings selectively in the olfactory tubercle, septum, substantia nigra and frontal cortex but not the striatum at dose levels which preferentially block apomorphine (APO) induced hyperactivity. The maximal prevention of specific 3H-spiperone binding by l-sulpiride and clozapine reached 60-80% in the former structures while the displacement of striatal 3H-spiperone binding did not exceed 40%. In contrast to l-sulpiride, thioridazine and clozapine both chlorpromazine and haloperidol reduced the 3H-spiperone binding to the same extent in all regions studied. Chlorpromazine and haloperidol were potent in prevention of striatal 3H-spiperone binding in vivo which reached 60-80% in this structure. (Author)

  11. Regional blockade by neuroleptic drugs of in vivo /sup 3/H-spiperone binding in the rat brain. Relation to blockade of apomorphine induced hyperactivity and stereotypies

    Energy Technology Data Exchange (ETDEWEB)

    Koehler, C.; Haglund, L.; Oegren, S.O.; Aengeby, T. (Astra Lackemedel AB, Soedertaelje (Sweden). Dept. of Pharmacology)

    1981-01-01

    The regional prevention by neuroleptic drugs of specific in vivo /sup 3/H-spiperone binding was studied in the rat brain. L-sulpiride, thioridazine and clozapine were found to reduce the /sup 3/H-spiperone bindings selectively in the olfactory tubercle, septum, substantia nigra and frontal cortex but not the striatum at dose levels which preferentially block apomorphine (APO) induced hyperactivity. The maximal prevention of specific /sup 3/H-spiperone binding by l-sulpiride and clozapine reached 60-80% in the former structures while the displacement of striatal /sup 3/H-spiperone binding did not exceed 40%. In contrast to l-sulpiride, thioridazine and clozapine both chlorpromazine and haloperidol reduced the /sup 3/H-spiperone binding to the same extent in all regions studied. Chlorpromazine and haloperidol were potent in prevention of striatal /sup 3/H-spiperone binding in vivo which reached 60-80% in this structure.

  12. Relevance of dorsal raphe nucleus firing in serotonin 5-HT2C receptor blockade-induced augmentation of SSRIs effects

    NARCIS (Netherlands)

    Sotty, Florence; Folgering, Joost H. A.; Brennum, Lise T.; Hogg, Sandra; Mork, Arne; Hertel, Peter; Cremers, Thomas I. F. H.

    2009-01-01

    Selective serotonin reuptake inhibitors are the most widely prescribed antidepressant drugs. However, they exhibit a slow onset of action, putatively due to the initial decrease in serotonin cell firing mediated via somato-dendritic autoreceptors. Interestingly, blockade of 5-HT2C receptors signific

  13. Long-Term Unemployment in the Varieties of Capitalism

    OpenAIRE

    Alberto Chilosi

    2014-01-01

    This paper considers how the different varieties of capitalism affect the rate of long-term unemployment. The liberal market variety, where employment protection is the lowest, presents lower rates of long-term unemployment than the continental European, or the Mediterranean varieties. In the latter both employment protection and long-term unemployment are the highest and labour market participation the lowest. But the social-democratic Scandinavian variety gets the best of both worlds: low r...

  14. Long-Term Inflation Outcomes after Hyperinflation: Theory and Evidence

    OpenAIRE

    Federico Guerrero

    2006-01-01

    This paper does two things. First, it shows both anecdotal and cross-country evidence that indicates that countries that have experienced hyperinflation display significantly lower long-term rates of inflation than countries that lack the same experience. Secondly, it presents a model to rationalize the main empirical finding. There is more than one mechanism through which the long-term effects of hyperinflation may have an impact on long-term inflation outcomes. The suggested explanation thi...

  15. The Uneasy Case for Favoring Long-Term Shareholders

    OpenAIRE

    Jesse M. Fried

    2015-01-01

    This paper challenges a persistent and pervasive view in corporate law and corporate governance: that a firm’s managers should favor long-term shareholders over short-term shareholders, and maximize long-term shareholders’ returns rather than the short-term stock price. Underlying this view is a strongly-held intuition that taking steps to increase long-term shareholder returns will generate a larger economic pie over time. But this intuition, I show, is flawed. Long-term shareholders, like s...

  16. Induction of long-term potentiation and long-term depression is cell-type specific in the spinal cord.

    Science.gov (United States)

    Kim, Hee Young; Jun, Jaebeom; Wang, Jigong; Bittar, Alice; Chung, Kyungsoon; Chung, Jin Mo

    2015-04-01

    The underlying mechanism of chronic pain is believed to be changes in excitability in spinal dorsal horn (DH) neurons that respond abnormally to peripheral input. Increased excitability in pain transmission neurons, and depression of inhibitory neurons, are widely recognized in the spinal cord of animal models of chronic pain. The possible occurrence of 2 parallel but opposing forms of synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD) was tested in 2 types of identified DH neurons using whole-cell patch-clamp recordings in mouse spinal cord slices. The test stimulus was applied to the sensory fibers to evoke excitatory postsynaptic currents in identified spinothalamic tract neurons (STTn) and GABAergic neurons (GABAn). Afferent conditioning stimulation (ACS) applied to primary afferent fibers with various stimulation parameters induced LTP in STTn but LTD in GABAn, regardless of stimulation parameters. These opposite responses were further confirmed by simultaneous dual patch-clamp recordings of STTn and GABAn from a single spinal cord slice. Both the LTP in STTn and the LTD in GABAn were blocked by an NMDA receptor antagonist, AP5, or an intracellular Ca chelator, BAPTA. Both the pattern and magnitude of intracellular Ca after ACS were almost identical between STTn and GABAn based on live-cell calcium imaging. The results suggest that the intense sensory input induces an NMDA receptor-dependent intracellular Ca increase in both STTn and GABAn, but produces opposing synaptic plasticity. This study shows that there is cell type-specific synaptic plasticity in the spinal DH. PMID:25785524

  17. Long-term stability of bentonite. A literature review

    International Nuclear Information System (INIS)

    The long-term thermodynamic stability of the bentonite buffer in the evolving chemical, thermal and hydrological conditions at Olkiluoto has been evaluated by reviewing the relevant experimental data and natural occurrences of bentonite that could serve as analogues for the long-term bentonite stability in the expected repository conditions, especially focussing on mineral transformations due, among others, to thermal effects including cementation. Natural occurrences with stable smectite have been reviewed and compared with Olkiluoto groundwater compositions at present and during the expected hydrogeochemical evolution of the repository. Alteration of the bentonite buffer is expected to be insignificant for natural groundwater conditions at present and for the evolving groundwater conditions at the expected thermal boundary conditions caused by the heat induced from the fuel canisters (+ and SiO2 and elevated pH due to degradation and dissolution processes. These may alter the conditions in the repository that may favour alteration and cementation processes. The amounts of foreign materials to be used in the repository will be updated along with the progress of the construction. Also the information on their impact on the barriers needs to be evaluated in more detail, including the degradation rate, mobility or dilution of the foreign materials in the repository environment. The exchangeable cation composition of the buffer bentonite is expected to equilibrate with the surrounding groundwater during and after saturation. This process is expected to lead towards Ca-dominant exchangeable cation composition within the montmorillonite interlayer spaces in the buffer. In general it seems that the transformation towards Ca-dominated composition would favour the long-term stability of the buffer as Ca-dominated smectite (compared to Na-dominated type) has larger water retention capacity and anion incorporation to the interlayer space of montmorillonite is more extensive

  18. Coupling giant impacts and long-term evolution models

    Science.gov (United States)

    Golabek, G. J.; Emsenhuber, A.; Jutzi, M.; Gerya, T. V.; Asphaug, E. I.

    2015-10-01

    The crustal dichotomy [1] is the dominant geological feature on planet Mars. The exogenic approach to the origin of the crustal dichotomy [2-6] assumes that the northern lowlands correspond to a giant impact basin formed after primordial crust formation. However these simulations only consider the impact phase without studying the long-term repercussions of such a collision. The endogenic approach [7], suggesting a degree-1 mantle upwelling underneath the southern highlands [8-11], relies on a high Rayleigh number and a particular viscosity profile to form a low degree convective pattern within the geological constraints for the dichotomy formation. Such vigorous convection, however, results in continuous magmatic resurfacing, destroying the initially dichotomous crustal structure in the long-term. A further option is a hybrid exogenic-endogenic approach [12-15], which proposes an impact-induced magma ocean and subsequent superplume in the southern hemisphere. However these models rely on simple scaling laws to impose the thermal effects of the collision. Here we present the first results of impact simulations performed with a SPH code [16,17] serially coupled with geodynamical computations performed using the code I3VIS [18] to improve the latter approach and test it against observations. We are exploring collisions varying the impactor velocities, impact angles and target body properties, and are gauging the sensitivity to the handoff from SPH to I3VIS. As expected, our first results indicate the formation of a transient hemispherical magma ocean in the impacted hemisphere, and the merging of the cores. We also find that impact angle and velocity have a strong effect on the post-impact temperature field [5] and on the timescale and nature of core merger.

  19. Blockade of CD26-mediated T cell costimulation with soluble caveolin-1-Ig fusion protein induces anergy in CD4+T cells

    International Nuclear Information System (INIS)

    CD26 binds to caveolin-1 in antigen-presenting cells (APC), and that ligation of CD26 by caveolin-1 induces T cell proliferation in a TCR/CD3-dependent manner. We report herein the effects of CD26-caveolin-1 costimulatory blockade by fusion protein caveolin-1-Ig (Cav-Ig). Soluble Cav-Ig inhibits T cell proliferation and cytokine production in response to recall antigen, or allogeneic APC. Our data hence suggest that blocking of CD26-associated signaling by soluble Cav-Ig may be an effective approach as immunosuppressive therapy.

  20. Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25.

    Science.gov (United States)

    Hannani, Dalil; Vétizou, Marie; Enot, David; Rusakiewicz, Sylvie; Chaput, Nathalie; Klatzmann, David; Desbois, Melanie; Jacquelot, Nicolas; Vimond, Nadège; Chouaib, Salem; Mateus, Christine; Allison, James P; Ribas, Antoni; Wolchok, Jedd D; Yuan, Jianda; Wong, Philip; Postow, Michael; Mackiewicz, Andrzej; Mackiewicz, Jacek; Schadendorff, Dirk; Jaeger, Dirk; Zörnig, Inka; Hassel, Jessica; Korman, Alan J; Bahjat, Keith; Maio, Michele; Calabro, Luana; Teng, Michele Wl; Smyth, Mark J; Eggermont, Alexander; Robert, Caroline; Kroemer, Guido; Zitvogel, Laurence

    2015-02-01

    The cytotoxic T lymphocyte antigen-4 (CTLA-4)-blocking antibody ipilimumab induces immune-mediated long-term control of metastatic melanoma in a fraction of patients. Although ipilimumab undoubtedly exerts its therapeutic effects via immunostimulation, thus far clinically useful, immunologically relevant biomarkers that predict treatment efficiency have been elusive. Here, we show that neutralization of IL-2 or blocking the α and β subunits of the IL-2 receptor (CD25 and CD122, respectively) abolished the antitumor effects and the accompanying improvement of the ratio of intratumoral T effector versus regulatory cells (Tregs), which were otherwise induced by CTLA-4 blockade in preclinical mouse models. CTLA-4 blockade led to the reduction of a suppressive CD4(+) T cell subset expressing Lag3, ICOS, IL-10 and Egr2 with a concomitant rise in IL-2-producing effector cells that lost FoxP3 expression and accumulated in regressing tumors. While recombinant IL-2 improved the therapeutic efficacy of CTLA-4 blockade, the decoy IL-2 receptor α (IL-2Rα, sCD25) inhibited the anticancer effects of CTLA-4 blockade. In 262 metastatic melanoma patients receiving ipilimumab, baseline serum concentrations of sCD25 represented an independent indicator of overall survival, with high levels predicting resistance to therapy. Altogether, these results unravel a role for IL-2 and IL-2 receptors in the anticancer activity of CTLA-4 blockade. Importantly, our study provides the first immunologically relevant biomarker, namely elevated serum sCD25, that predicts resistance to CTLA-4 blockade in patients with melanoma. PMID:25582080

  1. Standards for Psychological Services in Long-Term Care Facilities.

    Science.gov (United States)

    Morrow-Howell, Nancy; Lichtenberg, Peter A.; Smith, Michael; Frazer, Deborah; Molinari, Victor; Rosowsky, Erlene; Crose, Royda; Stillwell, Nick; Kramer, Nanette; Hartman-Stein, Paula; Qualls, Sara; Salamon, Michael; Duffy, Michael; Parr, Joyce; Gallagher-Thompson, Dolores

    1998-01-01

    Describes the development of standards for psychological practice in long-term care facilities. The standards, which were developed by Psychologists in Long-Term Care, address provider characteristics, methods of referral, assessment practices, treatment, and ethical issues. Offers suggestions for use of the standards. (MKA)

  2. Factors associated with long-term mortality in acute pancreatitis

    DEFF Research Database (Denmark)

    Nøjgaard, Camilla; Matzen, Peter; Bendtsen, Flemming;

    2011-01-01

    Knowledge of the long-term prognosis of acute pancreatitis (AP) is limited. The aims were to investigate: (1) prognostic factors associated with long-term mortality in patients with AP; (2) whether or not the level of serum (S-)amylase at admission had an impact on the prognosis; (3) causes of...

  3. How Does Long-Term Finance Affect Economic Volatility?

    OpenAIRE

    Demirguc-Kunt, Asli; BÁLINT L. HORVÁTH; Huizinga, Harry

    2016-01-01

    This paper examines how the ability to access long-term debt affects firm-level growth volatility. The analysis finds that firms in industries with stronger preference to use long-term finance relative to short-term finance experience lower growth volatility in countries with better-developed financial systems, as these firms may benefit from reduced refinancing risk. Institutions that fac...

  4. [Developing the core competencies of long-term care professionals].

    Science.gov (United States)

    Chen, Huey-Tzy; Lee, Kuang-Ting

    2012-12-01

    Longer average life expectancies and an ageing society have made long-term care an urgent and important issue in Taiwan. Although the implementation of Long-Term Care Ten-year Project four years ago has begun showing success in terms of assessing Taiwan's needs in terms of long-term care services and resources, there has been little forward progress in terms of training, recruiting and maintaining more competent professionals in the long-term care sector. This paper explores the current state of long-term care competency in Taiwan and educational strategies in place to improve the competency of long-term care professionals. Results indicate that the term geriatric competency embraces sub-competencies in direct care, communication, assessment, teamwork, cultural sensitivities and career care competencies. The term long-term care competency embraces the sub-competencies of supervision, management, information technology, resource management, and organizational skill. As a main contributor to effective long-term care, the nursing profession must employ effective strategies to develop competency-based education. Also, the profession must have an adequate supply of competent manpower to effectively respond to Taiwan's aging society. PMID:23212250

  5. Long-term hearing preservation in vestibular schwannoma

    DEFF Research Database (Denmark)

    Stangerup, Sven-Eric; Thomsen, Jens; Tos, Mirko;

    2010-01-01

    The aim of the present study was to evaluate the long-term hearing during "wait and scan" management of vestibular schwannomas.......The aim of the present study was to evaluate the long-term hearing during "wait and scan" management of vestibular schwannomas....

  6. Helping People Make Better Long-Term-Care Decisions

    Science.gov (United States)

    Kane, Robert L.; Boston, Krista; Chilvers, Mary

    2007-01-01

    Purpose: The purpose of this article is to describe an innovative online system to support long-term-care decision making. Design and Methods: The Long-Term Care Choices tool is a web-based system that uses expert opinion and structures decision making. Results: The system has been well accepted, and most users find it easy to use. Implications:…

  7. Determinants of long-term renal allograft outcome

    NARCIS (Netherlands)

    Leeuwen-Artz, M.A.

    2005-01-01

    Long-term renal allograft survival is markedly affected by premature death with a functioning graft, chronic allograft nephropathy, and recurrence of the original kidney disease. To improve long-term graft survival, focus is shifting from the prevention of acute rejections to the recognition and tre

  8. 24 CFR 971.5 - Long-term viability.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Long-term viability. 971.5 Section... ASSESSMENT OF THE REASONABLE REVITALIZATION POTENTIAL OF CERTAIN PUBLIC HOUSING REQUIRED BY LAW § 971.5 Long-term viability. (a) Reasonable investment. (1) Proposed revitalization costs for viability must...

  9. Interim analysis in long-term clinical trials

    NARCIS (Netherlands)

    G.A. van Es (Gerrit Anne)

    1990-01-01

    textabstractThe purpose of this dissertation is to evaluate the usefulness of both stopping rules and estimation methods in long-term clinical trials with interim analyses. The ASPECT trial, a long-term clinical trial to assess the effect of anticoagulant therapy on mortality in patients after myoca

  10. Mitochondrial impairment induced by postnatal ActRIIB blockade does not alter function and energy status in exercising mouse glycolytic muscle in vivo.

    Science.gov (United States)

    Béchir, Nelly; Pecchi, Émilie; Relizani, Karima; Vilmen, Christophe; Le Fur, Yann; Bernard, Monique; Amthor, Helge; Bendahan, David; Giannesini, Benoît

    2016-04-01

    Because it leads to a rapid and massive muscle hypertrophy, postnatal blockade of the activin type IIB receptor (ActRIIB) is a promising therapeutic strategy for counteracting muscle wasting. However, the functional consequences remain very poorly documented in vivo. Here, we have investigated the impact of 8-wk ActRIIB blockade with soluble receptor (sActRIIB-Fc) on gastrocnemius muscle anatomy, energy metabolism, and force-generating capacity in wild-type mice, using totally noninvasive magnetic resonance imaging (MRI) and dynamic(31)P-MRS. Compared with vehicle (PBS) control, sActRIIB-Fc treatment resulted in a dramatic increase in body weight (+29%) and muscle volume (+58%) calculated from hindlimb MR imaging, but did not alter fiber type distribution determined via myosin heavy chain isoform analysis. In resting muscle, sActRIIB-Fc treatment induced acidosis and PCr depletion, thereby suggesting reduced tissue oxygenation. During an in vivo fatiguing exercise (6-min repeated maximal isometric contraction electrically induced at 1.7 Hz), maximal and total absolute forces were larger in sActRIIB-Fc treated animals (+26 and +12%, respectively), whereas specific force and fatigue resistance were lower (-30 and -37%, respectively). Treatment with sActRIIB-Fc further decreased the maximal rate of oxidative ATP synthesis (-42%) and the oxidative capacity (-34%), but did not alter the bioenergetics status in contracting muscle. Our findings demonstrate in vivo that sActRIIB-Fc treatment increases absolute force-generating capacity and reduces mitochondrial function in glycolytic gastrocnemius muscle, but this reduction does not compromise energy status during sustained activity. Overall, these data support the clinical interest of postnatal ActRIIB blockade. PMID:26837807

  11. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma

    OpenAIRE

    Phan, Giao Q.; Yang, James C.; Sherry, Richard M.; Hwu, Patrick; Topalian, Suzanne L.; Schwartzentruber, Douglas J.; Restifo, Nicholas P; Haworth, Leah R.; Seipp, Claudia A.; Freezer, Linda J.; Morton, Kathleen E.; Mavroukakis, Sharon A.; Duray, Paul H.; Steinberg, Seth M.; Allison, James P.

    2003-01-01

    Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical immunoregulatory molecule (expressed on activated T cells and a subset of regulatory T cells) capable of down-regulating T cell activation. Blockade of CTLA-4 has been shown in animal models to improve the effectiveness of cancer immunotherapy. We thus treated 14 patients with metastatic melanoma by using serial i.v. administration of a fully human anti-CTLA-4 antibody (MDX-010) in conjunction with s.c....

  12. Long-Term Dynamics of Autonomous Fractional Differential Equations

    Science.gov (United States)

    Liu, Tao; Xu, Wei; Xu, Yong; Han, Qun

    This paper aims to investigate long-term dynamic behaviors of autonomous fractional differential equations with effective numerical method. The long-term dynamic behaviors predict where systems are heading after long-term evolution. We make some modification and transplant cell mapping methods to autonomous fractional differential equations. The mapping time duration of cell mapping is enlarged to deal with the long memory effect. Three illustrative examples, i.e. fractional Lotka-Volterra equation, fractional van der Pol oscillator and fractional Duffing equation, are studied with our revised generalized cell mapping method. We obtain long-term dynamics, such as attractors, basins of attraction, and saddles. Compared with some existing stability and numerical results, the validity of our method is verified. Furthermore, we find that the fractional order has its effect on the long-term dynamics of autonomous fractional differential equations.

  13. Reversibility of stress-echo induced ST-segment depression by long-term oral n-3 PUFA supplementation in subjects with chest pain syndrome, normal wall motion at stress-echo and normal coronary angiogram

    OpenAIRE

    Ziacchi Vigilio; Gaibazzi Nicola

    2004-01-01

    Abstract Background Normal coronary arteries may coexist with abnormal coronary and systemic endothelial function in patients with chest pain. Recent work by the renowned Pisa echo-group elegantly suggests that isolated ST-segment depression during stress-echo (SE) can be used as a marker of coronary endothelial dysfunction, in the absence of stress-inducible wall motion abnormalities and in the absence of angiographically-significant coronary artery disease (CAD). The long chain n-3 polyunsa...

  14. The Womanly World of Long Term Care: The Plight of the Long Term Care Worker. Gray Paper.

    Science.gov (United States)

    Older Women's League, Washington, DC.

    Long-term care workers (those who are paid to provide custodial care for long-term patients in nursing homes or at home) must care for a growing number of increasingly disabled or dependent persons. They are working for agencies and institutions under growing pressure to increase productivity. They face new training and competency requirements,…

  15. Long-Term Stewardship Baseline Report and Transition Guidance

    Energy Technology Data Exchange (ETDEWEB)

    Kristofferson, Keith

    2001-11-01

    Long-term stewardship consists of those actions necessary to maintain and demonstrate continued protection of human health and the environment after facility cleanup is complete. As the Department of Energy’s (DOE) lead laboratory for environmental management programs, the Idaho National Engineering and Environmental Laboratory (INEEL) administers DOE’s long-term stewardship science and technology efforts. The INEEL provides DOE with technical, and scientific expertise needed to oversee its long-term environmental management obligations complexwide. Long-term stewardship is administered and overseen by the Environmental Management Office of Science and Technology. The INEEL Long-Term Stewardship Program is currently developing the management structures and plans to complete INEEL-specific, long-term stewardship obligations. This guidance document (1) assists in ensuring that the program leads transition planning for the INEEL with respect to facility and site areas and (2) describes the classes and types of criteria and data required to initiate transition for areas and sites where the facility mission has ended and cleanup is complete. Additionally, this document summarizes current information on INEEL facilities, structures, and release sites likely to enter long-term stewardship at the completion of DOE’s cleanup mission. This document is not intended to function as a discrete checklist or local procedure to determine readiness to transition. It is an overarching document meant as guidance in implementing specific transition procedures. Several documents formed the foundation upon which this guidance was developed. Principal among these documents was the Long-Term Stewardship Draft Technical Baseline; A Report to Congress on Long-Term Stewardship, Volumes I and II; Infrastructure Long-Range Plan; Comprehensive Facility Land Use Plan; INEEL End-State Plan; and INEEL Institutional Plan.

  16. Neural correlates of long-term intense romantic love

    OpenAIRE

    Acevedo, Bianca P.; Aron, Arthur; Fisher, Helen E.; Brown, Lucy L.

    2011-01-01

    The present study examined the neural correlates of long-term intense romantic love using functional magnetic resonance imaging (fMRI). Ten women and 7 men married an average of 21.4 years underwent fMRI while viewing facial images of their partner. Control images included a highly familiar acquaintance; a close, long-term friend; and a low-familiar person. Effects specific to the intensely loved, long-term partner were found in: (i) areas of the dopamine-rich reward and basal ganglia system,...

  17. Long-Term Mean Wind Profiles Based on Similarity Theory

    DEFF Research Database (Denmark)

    Kelly, Mark C.; Gryning, Sven-Erik

    2010-01-01

    We provide general forms for long-term mean wind profiles from similarity-based wind profiles, beginning with a probabilistic adaptation of Monin–Obukhov similarity theory. We develop an analytical formulation for the stability distributions prevailing in the atmospheric surface layer, which in...... turn facilitates the derivation of a long-term mean wind profile based on Monin–Obukhov similarity theory. The modelled stability distributions exhibit good agreement with measurements from sites having different local conditions. The long-term wind profile formulation is further extended to include...

  18. 妊娠高血压综合征与远期脑血管病发生的关系%The relationship between pregnancy-induced hypertension syndrome and long-term cerebrovascular disease

    Institute of Scientific and Technical Information of China (English)

    吴利荣; 张婧

    2015-01-01

    Objective To investigate the relationship between pregnancy‐induced hypertension syndrome and long‐term ce‐rebrovascular disease. Methods Totally 238 patients with pregnancy‐induced hypertension syndrome were considered as obser‐vation group ,and 320 normal pregnancy women were considered as control group. The long‐term cerebrovascular disease oc‐currence and clinical characteristics between two groups were compared.Results The living area ,body mass index ,gestational age ,gestational age ,neonatal birth weight and education degree between two groups had statistical difference. The morbidity of cerebrovascular disease in observation group (10.1% ) was higher than that in control group (4.1% ) during follow‐up, which had statistical difference. There were no statistical difference in the parity and neonatal height of two groups. Cox pro‐portional hazards regression models showed that pregnancy‐induced hypertension syndrome was an independence risk factor of long‐term cerebrovascular disease. Conclusion Pregnancy‐induced hypertension syndrome has its own clinical characteristics and is an independence factor for long‐term cerebrovascular disease.%目的:探讨妊娠高血压综合征与远期脑血管病的关系。方法选择2002‐01—2012‐01收治的238例妊娠高血压患者为观察组研究对象,选择同期诊治的320例正常孕产妇为对照组研究对象。比较2组患者临床特点及远期脑血管病的发生情况。结果2组患者居住地区、体重指数、孕周、妊娠年龄、新生儿出生体质量及文化程度差别具有统计学意义(P<0.05);2组产次及新生儿身高差别无统计学意义( P>0.05);随访期间观察组患者脑血管病发病率为10.1%,显著高于对照组4.1%,差别具有统计学意义(P<0.05);Cox比例风险回归模型分析结果显示:妊娠高血压综合征为脑血管病发病的独立风险因素。结论妊娠高血压患者

  19. Impact of energy conservation policy measures on innovation, investment and long-term development of the Swiss economy. Results from the computable induced technical change and energy (CITE) model - Final report

    Energy Technology Data Exchange (ETDEWEB)

    Bretschger, L.; Ramer, R.; Schwark, F.

    2010-09-15

    This comprehensive final report for the Swiss Federal Office of Energy (SFOE) presents the results of a study made on the Computable Induced Technical Change and Energy (CITE) model. The authors note that, in the past two centuries, the Swiss economy experienced an unprecedented increase in living standards. At the same time, the stock of various natural resources declined and the environmental conditions changed substantially. The evaluation of the sustainability of a low energy and low carbon society as well as an optimum transition to this state is discussed. An economic analysis is made and the CITE and GCE (Computable General Equilibrium) numerical simulation models are discussed. The results obtained are presented and discussed.

  20. Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat

    OpenAIRE

    Blanco-Calvo, Eduardo; Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Galeano, Pablo; Rubio, Leticia; Suárez, Juan; Rodriguez de Fonseca, Fernando

    2014-01-01

    Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alter...