Effects of long-term, low dose rate fission neutron irradiation on the peripheral hematological cells in rats

International Nuclear Information System (INIS)

Jiang Dingwen; Lei Chengxiang; Shen Xianrong; Ma Li; Yang Xufang; Peng Wulin; Dai Shourong

2008-01-01

Objective: To evaluate the effects of long-term, low dose rate fission neutron irradiation on the peripheral hematological cells in rats. Methods: 96 rats were randomly divided into the control group and the irradiation group with low dose rate fission neutron ( 252 Cf, 0.35 mGy/h) irradiation 20.5 h every day. 8 rats of each group were killed at 14 d, 28 d, 42d, 56d, 70d after irradiation and 35d after the irradiation, and their peripheral hematological cells were tested respectively. Results: Compared with the control group, peripheral blood WBC was reduced significantly at the dose of 0.3Gy and 0.4Gy (P < 0.05), and was reduced remarkably at dose of 0.5Gy (P<0.01) and 35d after stopping irradiation(P<0.01). At dose of 0.2Gy, Peripheral blood RBC was abnormally higher comparing with the control group (P<0.01), accompanying with higher HCT and HGB, which suggests condensed blood. At the other point, RBC tend to become lower, but only at dose 0.5Gy, and the difference is significant comparing with control group(P <0.05). At dose of 0.3Gy, 0.4Gy and 0.5Gy, HCT were significantly lower comparing with control group. Comparing with control group, MCV was higher at 35d after stopping irradiation, and PLT was significantly lower in dose of 0.2Gy. Conclusion: Long-term irradiation with low dose rate fission neutron could significantly reduce peripheral blood WBC, with less effects on RBC and PLT. The reduced WBC could not recover at 35d after stopping irradiation. (authors)

HDAC inhibition modulates hippocampus-dependent long-term memory for object location in a CBP-dependent manner

Science.gov (United States)

Haettig, Jakob; Stefanko, Daniel P.; Multani, Monica L.; Figueroa, Dario X.; McQuown, Susan C.; Wood, Marcelo A.

2011-01-01

Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation required for long-term memory. Several studies have shown that CBP and histone acetylation are necessary for hippocampus-dependent long-term memory and hippocampal long-term potentiation (LTP). Importantly, every genetically modified Cbp mutant mouse exhibits long-term memory impairments in object recognition. However, the role of the hippocampus in object recognition is controversial. To better understand how chromatin-modifying enzymes modulate long-term memory for object recognition, we first examined the role of the hippocampus in retrieval of long-term memory for object recognition or object location. Muscimol inactivation of the dorsal hippocampus prior to retrieval had no effect on long-term memory for object recognition, but completely blocked long-term memory for object location. This was consistent with experiments showing that muscimol inactivation of the hippocampus had no effect on long-term memory for the object itself, supporting the idea that the hippocampus encodes spatial information about an object (such as location or context), whereas cortical areas (such as the perirhinal or insular cortex) encode information about the object itself. Using location-dependent object recognition tasks that engage the hippocampus, we demonstrate that CBP is essential for the modulation of long-term memory via HDAC inhibition. Together, these results indicate that HDAC inhibition modulates memory in the hippocampus via CBP and that different brain regions utilize different chromatin-modifying enzymes to regulate learning and memory. PMID:21224411

Effects of long-term low dose radiation. Epstein-Barr virus-specific antibodies in radiological technologists

Energy Technology Data Exchange (ETDEWEB)

Kumagai, Etsuko; Higashida, Yoshiharu; Onomichi, Mitsukazu; Nakamura, Ikuo; Tanoue, Shozo; Tanaka, Ryuji; Kumagai, Takashi; Katsuki, Takato; Sawada, Shozo.

1988-09-01

To clarify the long-term effects of occupational exposure to low doses of radiation, Epstein-Barr virus (EBV)-specific antibody titers in sera from 104 radiological technologists (R.T.) and 118 controls in Kumamoto prefecture were measured by the immunofluorescence method. Antibody titers to viral capsid antigen (VCA)-IgG increased with the years of experience as R.T., and the prevalence of abnormal antibody titers to both VCA-IgG and early antigen (EA)-IgG were significantly higher in R.T. with over 15 years of experience or 30 rads of cumulative radiation dose than in the controls. However, there was no correlation between exposure and the frequency of abnormal EBV-associated nuclear antigen (EBNA) antibody titers. The EBV-specific antibody titers of 24 Hiroshima atomic-bomb survivors were also measured. They were similar to those of the R.T. with over 30 years of experience. The EBV-specific antibody titers of R.T. suggest that there may be an impairment of immunologic competence after continuous long-term exposure to low doses of radiation. Also, the correlation of EBV-specific antibody titers and frequency of cells with chromosome aberrations in 53 R.T. was studied. Some correlations were found between the antibody titers to both of the VCA-IgG and EBNA and the frequency of cells with chromosome aberrations.

Multidetector CT radiation dose optimisation in adults: short- and long-term effects of a clinical audit

International Nuclear Information System (INIS)

Tack, Denis; Jahnen, Andreas; Kohler, Sarah; Harpes, Nico; Back, Carlo; Maertelaer, Viviane de; Gevenois, Pierre Alain

2014-01-01

To report short- and long-term effects of an audit process intended to optimise the radiation dose from multidetector row computed tomography (MDCT). A survey of radiation dose from all eight MDCT departments in the state of Luxembourg performed in 2007 served as baseline, and involved the most frequently imaged regions (head, sinus, cervical spine, thorax, abdomen, and lumbar spine). CT dose index volume (CTDIvol), dose-length product per acquisition (DLP/acq), and DLP per examination (DLP/exa) were recorded, and their mean, median, 25th and 75th percentiles compared. In 2008, an audit conducted in each department helped to optimise doses. In 2009 and 2010, two further surveys evaluated the audit's impact on the dose delivered. Between 2007 and 2009, DLP/exa significantly decreased by 32-69 % for all regions (P < 0.001) except the lumbar spine (5 %, P = 0.455). Between 2009 and 2010, DLP/exa significantly decreased by 13-18 % for sinus, cervical and lumbar spine (P ranging from 0.016 to less than 0.001). Between 2007 and 2010, DLP/exa significantly decreased for all regions (18-75 %, P < 0.001). Collective dose decreased by 30 % and the 75th percentile (diagnostic reference level, DRL) by 20-78 %. The audit process resulted in long-lasting dose reduction, with DRLs reduced by 20-78 %, mean DLP/examination by 18-75 %, and collective dose by 30 %. (orig.)

Review of Cl-36 behaviour in the biosphere and implications for long-term dose assessment

International Nuclear Information System (INIS)

Leclerc, E.; Smith, G.; Lloyd, P.

2009-01-01

Cl-36 is an important contributor to potential radiation doses in the long term, arising from release into the biosphere from radioactive waste disposal facilities. Its special attributes include its long half-life, high mobility in many environmental conditions, and potentially high uptake into plants and hence accumulation in the food-chain. Review has shown very wide ranges of Cl-36 values of parameters commonly employed in models used for long term doses. Accordingly, a workshop was held recently within the aegis of the international collaboration project BIOPROTA, to consider the causes of such variation, and in particular: to provide an open forum for presentation and discussion of environmental processes involved in Cl-36 migration and accumulation, and on how to model them, and to develop recommendations for the direction of continuing research as input to long-term radiological assessment. Participation in the workshop included specialists and contributions from North America, Europe and Japan in environmental behaviour of chlorine, radioecology of Cl-36 and long term dose assessment. This paper will present the output from that workshop in the context of the wider aspects of performance assessment, taking into account information about: waste types for which Cl-36 is a significant component of the total Cl-36 inventory; data requirements for the dose assessment models, notably concerning uptake from soils into food crops which may lead to higher doses than direct consumption of contaminated drinking water; critical data weaknesses which may lead to overly pessimistic dose estimates; time dependent factors within a single growing season which can affect final concentrations in food crops for animals and humans; alternative conceptual models for the behaviour of Cl-36 in the environment, notably models structured as other trace radionuclide dose assessment models as opposed to models which are based specifically on chlorine behaviour which should take

Multidetector CT radiation dose optimisation in adults: short- and long-term effects of a clinical audit

Energy Technology Data Exchange (ETDEWEB)

Tack, Denis [EpiCURA Hospital, Clinique Louis Caty, Department of Radiology, Baudour (Belgium); Jahnen, Andreas; Kohler, Sarah [CRP Henri Tudor, Luxembourg (Luxembourg); Harpes, Nico; Back, Carlo [Ministry of Health, Department of Radiation Protection, Luxembourg (Luxembourg); Maertelaer, Viviane de [Universite libre de Bruxelles, Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire and SBIM, Statistical Unit, Brussels (Belgium); Gevenois, Pierre Alain [Hopital Erasme, Department of Radiology, Brussels (Belgium)

2014-01-15

To report short- and long-term effects of an audit process intended to optimise the radiation dose from multidetector row computed tomography (MDCT). A survey of radiation dose from all eight MDCT departments in the state of Luxembourg performed in 2007 served as baseline, and involved the most frequently imaged regions (head, sinus, cervical spine, thorax, abdomen, and lumbar spine). CT dose index volume (CTDIvol), dose-length product per acquisition (DLP/acq), and DLP per examination (DLP/exa) were recorded, and their mean, median, 25th and 75th percentiles compared. In 2008, an audit conducted in each department helped to optimise doses. In 2009 and 2010, two further surveys evaluated the audit's impact on the dose delivered. Between 2007 and 2009, DLP/exa significantly decreased by 32-69 % for all regions (P < 0.001) except the lumbar spine (5 %, P = 0.455). Between 2009 and 2010, DLP/exa significantly decreased by 13-18 % for sinus, cervical and lumbar spine (P ranging from 0.016 to less than 0.001). Between 2007 and 2010, DLP/exa significantly decreased for all regions (18-75 %, P < 0.001). Collective dose decreased by 30 % and the 75th percentile (diagnostic reference level, DRL) by 20-78 %. The audit process resulted in long-lasting dose reduction, with DRLs reduced by 20-78 %, mean DLP/examination by 18-75 %, and collective dose by 30 %. (orig.)

Verbal Short-Term Memory Span in Children: Long-Term Modality Dependent Effects of Intrauterine Growth Restriction

Science.gov (United States)

Geva, R.; Eshel, R.; Leitner, Y.; Fattal-Valevski, A.; Harel, S.

2008-01-01

Background: Recent reports showed that children born with intrauterine growth restriction (IUGR) are at greater risk of experiencing verbal short-term memory span (STM) deficits that may impede their learning capacities at school. It is still unknown whether these deficits are modality dependent. Methods: This long-term, prospective design study…

In vitro chondrocyte toxicity following long-term, high-dose exposure to Gd-DTPA and a novel cartilage-targeted MR contrast agent

Energy Technology Data Exchange (ETDEWEB)

Midura, Sharon; Midura, Ronald J. [Cleveland Clinic, Biomedical Engineering, Lerner Research Institute, Cleveland, OH (United States); Schneider, Erika [Cleveland Clinic, Imaging Institute, A21, Cleveland, OH (United States); NitroSci Pharmaceuticals, New Berlin, WI (United States); Rosen, Gerald M. [University of Maryland School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD (United States); NitroSci Pharmaceuticals, New Berlin, WI (United States); Winalski, Carl S. [Cleveland Clinic, Biomedical Engineering, Lerner Research Institute, Cleveland, OH (United States); Cleveland Clinic, Imaging Institute, A21, Cleveland, OH (United States)

2017-01-15

To determine the concentrations exhibiting toxicity of a cartilage-targeted magnetic resonance imaging contrast agent compared with gadopentetate dimeglumine (Gd-DT-PA) in chondrocyte cultures. A long-term Swarm rat chondrosarcoma chondrocyte-like cell line was exposed for 48 h to 1.0-20 mM concentrations of diaminobutyl-linked nitroxide (DAB4-DLN) citrate, 1.0-20 mM Gd-DTPA, 1.0 μM staurosporine (positive control), or left untreated. Cell appearance, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays of metabolic activity, quantitative PicoGreen assays of DNA content, and calcein-AM viability assays were compared. At 1.0-7.5 mM, minimal decrease in cell proliferation was found for both agents. At all doses of both agents, cell culture appearances were similar after 24 h of treatment. At the higher doses, differences in cell culture appearance were found after 48 h of treatment, with dose-dependent declines in chondrocyte populations for both agents. Concentration-dependent declines in DNA content and calcein fluorescence were found after 48 h of treatment, but beginning at a lower dose of DAB4-DLN citrate than Gd-DTPA. Dose-dependent decreases in MTT staining (cell metabolism) were apparent for both agents, but larger effects were evident at a lower dose for DAB-DLN citrate. Poor MTT staining of cells exposed for 48 h to 20 mM DAB4-DLN citrate probably indicates dead or dying cells. The minimal effect of the long-term exposure of model chondrocyte cell cultures to DAB4-DLN citrate and Gd-DTPA concentrations up to 7.5 mM (3x typical arthrographic administration) is supporting evidence that these doses are acceptable for MR arthrography. The findings are reassuring given that the experimental exposure to the contrast agents at sustained concentrations was much longer than when used clinically. (orig.)

In vitro chondrocyte toxicity following long-term, high-dose exposure to Gd-DTPA and a novel cartilage-targeted MR contrast agent

International Nuclear Information System (INIS)

Midura, Sharon; Midura, Ronald J.; Schneider, Erika; Rosen, Gerald M.; Winalski, Carl S.

2017-01-01

To determine the concentrations exhibiting toxicity of a cartilage-targeted magnetic resonance imaging contrast agent compared with gadopentetate dimeglumine (Gd-DT-PA) in chondrocyte cultures. A long-term Swarm rat chondrosarcoma chondrocyte-like cell line was exposed for 48 h to 1.0-20 mM concentrations of diaminobutyl-linked nitroxide (DAB4-DLN) citrate, 1.0-20 mM Gd-DTPA, 1.0 μM staurosporine (positive control), or left untreated. Cell appearance, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays of metabolic activity, quantitative PicoGreen assays of DNA content, and calcein-AM viability assays were compared. At 1.0-7.5 mM, minimal decrease in cell proliferation was found for both agents. At all doses of both agents, cell culture appearances were similar after 24 h of treatment. At the higher doses, differences in cell culture appearance were found after 48 h of treatment, with dose-dependent declines in chondrocyte populations for both agents. Concentration-dependent declines in DNA content and calcein fluorescence were found after 48 h of treatment, but beginning at a lower dose of DAB4-DLN citrate than Gd-DTPA. Dose-dependent decreases in MTT staining (cell metabolism) were apparent for both agents, but larger effects were evident at a lower dose for DAB-DLN citrate. Poor MTT staining of cells exposed for 48 h to 20 mM DAB4-DLN citrate probably indicates dead or dying cells. The minimal effect of the long-term exposure of model chondrocyte cell cultures to DAB4-DLN citrate and Gd-DTPA concentrations up to 7.5 mM (3x typical arthrographic administration) is supporting evidence that these doses are acceptable for MR arthrography. The findings are reassuring given that the experimental exposure to the contrast agents at sustained concentrations was much longer than when used clinically. (orig.)

Mechanism underlying the effect of long-term exposure to low dose of pesticides on DNA integrity.

Science.gov (United States)

Alleva, Renata; Manzella, Nicola; Gaetani, Simona; Bacchetti, Tiziana; Bracci, Massimo; Ciarapica, Veronica; Monaco, Federica; Borghi, Battista; Amati, Monica; Ferretti, Gianna; Tomasetti, Marco

2018-04-01

Pesticides, including herbicides, insecticides and fungicides, are widely used in intensive agriculture. Recently, the long-term effects of pesticide exposure were found to be associated with many diseases. In this study, we evaluated the long-term effect of low-level exposure to a mixture of pesticides on DNA damage response (DDR) in relation to individual detoxifying variability. A residential population chronically exposed to pesticides was enrolled, biological/environmental pesticide levels; paroxonase 1 (PON-1) activity and 192 Q/R polymorphism and DDR were evaluated at three different periods of pesticide exposure. OGG1-dependent DNA repair activity was decreased in relation to pesticide exposure. The increase of DNA lesions and pesticide levels in the intensive pesticide-spraying period was independent on PON-1 activity. Next, human bronchial epithelial and neuronal cells were used as a model for in vitro evaluation of the mechanistic effect of pesticides. Pesticides induced mitochondrial dysfunction leading to ROS formation. ROS from mitochondria induced DNA damage, which in turn induced OGG1-dependent DNA repair activity through 8-oxoguanine DNA glycosylase 1 (OGG1) expression and activation. Even though OGG1 was overexpressed, an inhibition of its activity, associated with DNA lesion accumulation, was found at prolonged pesticide-exposure. A post-translational regulation of OGG1 by pesticide may be postulated. Taken together, long-term exposure to low-levels of pesticides affects DDR resulting in accumulation of DNA lesions that eventually may lead to cancer or neurological disorders. © 2018 Wiley Periodicals, Inc.

Verbal short-term memory span in children: long-term modality dependent effects of intrauterine growth restriction.

Science.gov (United States)

Geva, R; Eshel, R; Leitner, Y; Fattal-Valevski, A; Harel, S

2008-12-01

Recent reports showed that children born with intrauterine growth restriction (IUGR) are at greater risk of experiencing verbal short-term memory span (STM) deficits that may impede their learning capacities at school. It is still unknown whether these deficits are modality dependent. This long-term, prospective design study examined modality-dependent verbal STM functions in children who were diagnosed at birth with IUGR (n = 138) and a control group (n = 64). Their STM skills were evaluated individually at 9 years of age with four conditions of the Visual-Aural Digit Span Test (VADS; Koppitz, 1981): auditory-oral, auditory-written, visuospatial-oral and visuospatial-written. Cognitive competence was evaluated with the short form of the Wechsler Intelligence Scales for Children--revised (WISC-R95; Wechsler, 1998). We found IUGR-related specific auditory-oral STM deficits (p long-term relationship between prenatal aberrant head growth and auditory verbal STM deficits by the end of the first decade of life. Empirical, clinical and educational implications are presented.

Cannabinoids prevent the differential long-term effects of exposure to severe stress on hippocampal- and amygdala-dependent memory and plasticity.

Science.gov (United States)

Shoshan, Noa; Segev, Amir; Abush, Hila; Mizrachi Zer-Aviv, Tomer; Akirav, Irit

2017-10-01

Exposure to excessive or uncontrolled stress is a major factor associated with various diseases including posttraumatic stress disorder (PTSD). The consequences of exposure to trauma are affected not only by aspects of the event itself, but also by the frequency and severity of trauma reminders. It was suggested that in PTSD, hippocampal-dependent memory is compromised while amygdala-dependent memory is strengthened. Several lines of evidence support the role of the endocannabinoid (eCB) system as a modulator of the stress response. In this study we aimed to examine cannabinoids modulation of the long-term effects (i.e., 1 month) of exposure to a traumatic event on memory and plasticity in the hippocampus and amygdala. Following exposure to the shock and reminders model of PTSD in an inhibitory avoidance light-dark apparatus rats demonstrated: (i) enhanced fear retrieval and impaired inhibitory extinction (Ext), (ii) no long-term potentiation (LTP) in the CA1, (iii) impaired hippocampal-dependent short-term memory in the object location task, (iv) enhanced LTP in the amygdala, and (v) enhanced amygdala-dependent conditioned taste aversion memory. The cannabinoid CB1/2 receptor agonist WIN55-212,2 (0.5mg/kg, i.p.) and the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3mg/kg, i.p.), administered 2 hr after shock exposure prevented these opposing effects on hippocampal- and amygdala-dependent processes. Moreover, the effects of WIN55-212,2 and URB597 on Ext and acoustic startle were prevented by co-administration of a low dose of the CB1 receptor antagonist AM251 (0.5mg/kg, i.p.), suggesting that the preventing effects of both drugs are mediated by CB1 receptors. Exposure to shock and reminders increased CB1 receptor levels in the CA1 and basolateral amygdala 1 month after shock exposure and this increase was also prevented by administering WIN55-212,2 or URB597. Taken together, these findings suggest the involvement of the eCB system, and specifically CB1

Characterization of long-term dose stability of N-isopropylacrylamide polymer gel dosimetry

International Nuclear Information System (INIS)

Chang, Y.J.; Central Taiwan University of Science and Technology, Taichung City, Taiwan, ROC; Chen, C.H.; Hsieh, B.T.

2014-01-01

In this study, the detailed characteristics, including spatial uniformity, dose distributions, inter-batch variability, reproducibility, and long-term temporal stability, of N-isopropylacrylamide (NIPAM) polymer gel dosimeter were investigated. A commercial 10x fast optical computed tomography scanner (OCTOPUS TM -10×, MGS Research, Inc., Madison, CT, USA) was used to measure NIPAM polymer gel dosimeter. A cylindrical NIPAM gel phantom that measured 10 cm × 10 cm was irradiated via a single-field treatment plan with a field size of 4 cm × 4 cm. The maximum standard deviation of spatial uniformity for NIPAM gel was less than 0.29 %. The average standard deviation among the three batches of gel dosimeters was less than 1 %. The gamma pass rate could reach as high as 96.76 % when a 3 % dose difference and a 3 mm dose-to-agreement criteria were used. The long-term measurement of irradiated NIPAM gel dosimeter indicated that the dose maps attained a gradually stable value 15 h post-irradiation and remained stable until 72 h post-irradiation. The gamma pass rate could achieve a maximum value between 24 and 72 h post-irradiation. The edge enhancement effect that occurred around the irradiated region was observed 72 h post-irradiation. Thus, the results from this study suggest that NIPAM gel dosimeter should be measured approximately 24 h post-irradiation to reduce the occurrence of the edge enhancement effect. (author)

The long-term effectiveness of generic adult fixed-dose combination ...

African Journals Online (AJOL)

Background: Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs. Objective: To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment. Methods: ...

Long-term outcome in pyridoxine-dependent epilepsy

NARCIS (Netherlands)

Bok, L.A.; Halbertsma, F.J.; Houterman, S.; Wevers, R.A.; Vreeswijk, C.M.J.M.; Jakobs, C.; Struys, E.; van der Hoeven, J.H.; Sival, D.A.; Willemsen, M.A.

2012-01-01

Aim  The long-term outcome of the Dutch pyridoxine-dependent epilepsy cohort and correlations between patient characteristics and follow-up data were retrospectively studied. Method  Fourteen patients recruited from a national reference laboratory were included (four males, 10 females, from 11

Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

International Nuclear Information System (INIS)

Goenka, Anuj; Magsanoc, Juan Martin; Pei Xin; Schechter, Michael; Kollmeier, Marisa; Cox, Brett; Scardino, Peter T.; Eastham, James A.; Zelefsky, Michael J.

2012-01-01

Purpose: To review the impact of high–dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases–free survival, and to identify clinical and pathologic predictors of outcomes. Methods and Materials: During 1988–2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose ≥66 Gy, of whom 205 (72%) received doses ≥70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. Results: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases–free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p 0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score ≥7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose ≥70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose ≥70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07). Conclusion: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in patients with greater burden of disease at time of SRT as reflected by

Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

Energy Technology Data Exchange (ETDEWEB)

Goenka, Anuj; Magsanoc, Juan Martin; Pei Xin; Schechter, Michael; Kollmeier, Marisa; Cox, Brett [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Scardino, Peter T.; Eastham, James A. [Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

2012-09-01

Purpose: To review the impact of high-dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases-free survival, and to identify clinical and pathologic predictors of outcomes. Methods and Materials: During 1988-2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose {>=}66 Gy, of whom 205 (72%) received doses {>=}70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. Results: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p < 0.01), negative surgical margins (p < 0.01), presalvage PSA level >0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score {>=}7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose {>=}70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose {>=}70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07). Conclusion: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in

Acute ethanol has biphasic effects on short- and long-term memory in both foreground and background contextual fear conditioning in C57BL/6 mice.

Science.gov (United States)

Gulick, Danielle; Gould, Thomas J

2007-09-01

Ethanol is a frequently abused, addictive drug that impairs cognitive function. Ethanol may disrupt cognitive processes by altering attention, short-term memory, and/or long-term memory. Interestingly, some research suggests that ethanol may enhance cognitive processes at lower doses. The current research examined the dose-dependent effects of ethanol on contextual and cued fear conditioning. In addition, the present studies assessed the importance of stimulus salience in the effects of ethanol and directly compared the effects of ethanol on short-term and long-term memory. This study employed both foreground and background fear conditioning, which differ in the salience of contextual stimuli, and tested conditioning at 4 hours, 24 hours, and 1 week in order to assess the effects of ethanol on short-term and long-term memory. Foreground conditioning consisted of 2 presentations of a foot shock unconditioned stimulus (US) (2 seconds, 0.57 mA). Background conditioning consisted of 2 auditory conditioned stimulus (30 seconds, 85 dB white noise)-foot shock (US; 2 seconds, 0.57 mA) pairings. For both foreground and background conditioning, ethanol enhanced short-term and long-term memory for contextual and cued conditioning at a low dose (0.25 g/kg) and impaired short-term and long-term memory for contextual and cued conditioning at a high dose (1.0 g/kg). These results suggest that ethanol has long-lasting, biphasic effects on short-term and long-term memory for contextual and cued conditioning. Furthermore, the effects of ethanol on contextual fear conditioning are independent of the salience of the context.

Long-term effects of ionizing radiation on gene expression in a zebrafish model.

Directory of Open Access Journals (Sweden)

Lahcen Jaafar

Full Text Available Understanding how initial radiation injury translates into long-term effects is an important problem in radiation biology. Here, we define a set of changes in the transcription profile that are associated with the long-term response to radiation exposure. The study was performed in vivo using zebrafish, an established radiobiological model organism. To study the long-term response, 24 hour post-fertilization embryos were exposed to 0.1 Gy (low dose or 1.0 Gy (moderate dose of whole-body gamma radiation and allowed to develop for 16 weeks. Liver mRNA profiles were then analyzed using the Affymetrix microarray platform, with validation by quantitative PCR. As a basis for comparison, 16-week old adults were exposed at the same doses and analyzed after 4 hours. Statistical analysis was performed in a way to minimize the effects of multiple comparisons. The responses to these two treatment regimes differed greatly: 360 probe sets were associated primarily with the long-term response, whereas a different 2062 probe sets were associated primarily with the response when adults of the same age were irradiated 4 hours before exposure. Surprisingly, a ten-fold difference in radiation dose (0.1 versus 1.0 Gy had little effect. Analysis at the gene and pathway level indicated that the long-term response includes the induction of cytokine and inflammatory regulators and transcription and growth factors. The acute response includes the induction of p53 target genes and modulation of the hypoxia-induced transcription factor-C/EBP axis. Results help define genes and pathways affected in the long-term, low and moderate dose radiation response and differentiate them from those affected in an acute response in the same tissue.

Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior

Science.gov (United States)

Leclercq, Sophie; Mian, Firoz M.; Stanisz, Andrew M.; Bindels, Laure B.; Cambier, Emmanuel; Ben-Amram, Hila; Koren, Omry; Forsythe, Paul; Bienenstock, John

2017-01-01

There is increasing concern about potential long-term effects of antibiotics on children's health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice. We find that penicillin has lasting effects in both sexes on gut microbiota, increases cytokine expression in frontal cortex, modifies blood–brain barrier integrity and alters behaviour. The antibiotic-treated mice exhibit impaired anxiety-like and social behaviours, and display aggression. Concurrent supplementation with Lactobacillus rhamnosus JB-1 prevents some of these alterations. These results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria. PMID:28375200

Long-Term Outcome in Pyridoxine-Dependent Epilepsy

Science.gov (United States)

Bok, Levinus A.; Halbertsma, Feico J..; Houterman, Saskia; Wevers, Ron A.; Vreeswijk, Charlotte; Jakobs, Cornelis; Struys, Eduard; van der Hoeven, Johan H.; Sival, Deborah A.; Willemsen, Michel A.

2012-01-01

Aim: The long-term outcome of the Dutch pyridoxine-dependent epilepsy cohort and correlations between patient characteristics and follow-up data were retrospectively studied. Method: Fourteen patients recruited from a national reference laboratory were included (four males, 10 females, from 11 families; median age at assessment 6y; range 2y…

The Erlangen Dose Optimization Trial for radiotherapy of benign painful shoulder syndrome. Long-term results

International Nuclear Information System (INIS)

Ott, O.J.; Hertel, S.; Gaipl, U.S.; Frey, B.; Schmidt, M.; Fietkau, R.

2014-01-01

To evaluate the long-term efficacy of pain reduction by two dose-fractionation schedules for radiotherapy of painful shoulder syndrome. Between February 2006 and February 2010, 312 evaluable patients were recruited for this prospective trial. All patients received low-dose orthovoltage radiotherapy. One course consisted of 6 fractions in 3 weeks. In the case of insufficient pain remission after 6 weeks, a second course was administered. Patients were randomly assigned to one of two groups to receive single doses of either 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before radiotherapy, as well as immediately after (early response), 6 weeks after (delayed response) and approximately 3 years after (long-term response) completion of radiotherapy using a questionnaire-based visual analogue scale (VAS) and a comprehensive pain score (CPS). Median follow-up was 35 months (range 11-57). The overall early, delayed and long-term response rates for all patients were 83, 85 and 82%, respectively. The mean VAS scores before treatment and those for early, delayed and long-term response in the 0.5- and 1.0-Gy groups were 56.8±23.7 and 53.2±21.8 (p=0.16); 38.2±36.1 and 34.0±24.5 (p=0.19); 33.0±27.2 and 23.7±22.7 (p=0.04) and 27.9±25.8 and 32.1±26.9 (p=0.25), respectively. The mean CPS values before treatment and those for early, delayed and long-term response were 9.7±3.0 and 9.5±2.7 (p=0.31); 6.1±3.6 and 5.4±3.6 (p=0.10); 5.3±3.7 and 4.1±3.7 (p=0.05) and 4.0±3.9 and 5.3±4.4 (p=0.05), respectively. No significant differences in the quality of the long-term response were found between the 0.5- and 1.0-Gy arms (p=0.28). Radiotherapy is an effective treatment for the management of benign painful shoulder syndrome. For radiation protection reasons, the dose for a radiotherapy series should not exceed 3.0 Gy. (orig.)

Long-term persistence, density dependence and effects of climate change on rosyside dace (Cyprinidae)

Science.gov (United States)

Gary D. Grossman; Gary Sundin; Robert E. Ratajczak

2016-01-01

SummaryWe used long-term population data for rosyside dace (Clinostomus funduloides), a numerically dominant member of a stochastically organised fish assemblage, to evaluate the relative importance of density-dependent and density-independent processes to population...

Dose measurements and LET-determination in space station MIR during the Russian long term flight RLF

International Nuclear Information System (INIS)

Vana, N.; Schoener, N.; Fugger, M.; Akatov, Y.; Shurshakov, V.

1996-01-01

For determination of the absorbed dose and the dose equivalent in complex mixed radiation fields, new methods were developed in the frame of the Austrian-Soviet space mission AUSTROMIR in October 1991. The method utilizes the changes of peak height ratios in thermoluminescence glowcurves. Peak height ratios depend on the linear energy transfer (LET) of absorbed radiation. This effect was calibrated in different radiation fields (alpha-, beta-, gamma-, neutron fields and heavy charged particle beams). The method was approached for dose measurements during several space programs (DOSIMIR, BION-10, PHOTONS). During the Russian long term flight RLF six dosemeter packets were exposed in three different periods. Two positions with different shielding (the working area and the cabin of the board engineer) were chosen for the exposition of the dosemeters during each period in order to measure the variation of absorbed dose as well as the variation of average LET of absorbed radiation within the habitable part of space station MIR. These results will be compared with the results during two former periods of measurements on space station MIR (AUSTROMIR/DOSIMIR) and results obtained inside of biosatellite BION-10 and during the space shuttle mission STS-60. (author)

Short- and Long-Term Effects of Prenatal Exposure to Iron Oxide Nanoparticles: Influence of Surface Charge and Dose on Developmental and Reproductive Toxicity

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Kristin R. Di Bona

2015-12-01

Full Text Available Iron oxide nanoparticles (NPs are commonly utilized for biomedical, industrial, and commercial applications due to their unique properties and potential biocompatibility. However, little is known about how exposure to iron oxide NPs may affect susceptible populations such as pregnant women and developing fetuses. To examine the influence of NP surface-charge and dose on the developmental toxicity of iron oxide NPs, Crl:CD1(ICR (CD-1 mice were exposed to a single, low (10 mg/kg or high (100 mg/kg dose of positively-charged polyethyleneimine-Fe2O3-NPs (PEI-NPs, or negatively-charged poly(acrylic acid-Fe2O3-NPs (PAA-NPs during critical windows of organogenesis (gestation day (GD 8, 9, or 10. A low dose of NPs, regardless of charge, did not induce toxicity. However, a high exposure led to charge-dependent fetal loss as well as morphological alterations of the uteri (both charges and testes (positive only of surviving offspring. Positively-charged PEI-NPs given later in organogenesis resulted in a combination of short-term fetal loss (42% and long-term alterations in reproduction, including increased fetal loss for second generation matings (mice exposed in utero. Alternatively, negatively-charged PAA-NPs induced fetal loss (22% earlier in organogenesis to a lesser degree than PEI-NPs with only mild alterations in offspring uterine histology observed in the long-term.

SU-F-18C-11: Diameter Dependency of the Radial Dose Distribution in a Long Polyethylene Cylinder

Energy Technology Data Exchange (ETDEWEB)

Bakalyar, D; McKenney, S [Henry Ford Health System, Detroit, MI (United States); Feng, W [New York Presbyterian Hospital, Tenafly, NJ (United States)

2014-06-15

Purpose: The radial dose distribution in the central plane of a long cylinder following a long CT scan depends upon the diameter and composition of the cylinder. An understanding of this behavior is required for determining the spatial average of the dose in the central plane. Polyethylene, the material for construction of the TG200/ICRU phantom (30 cm in diameter) was used for this study. Size effects are germane to the principles incorporated in size specific dose estimates (SSDE); thus diameter dependency was explored as well. Method: ssuming a uniform cylinder and cylindrically symmetric conditions of irradiation, the dose distribution can be described using a radial function. This function must be an even function of the radial distance due to the conditions of symmetry. Two effects are accounted for: The direct beam makes its weakest contribution at the center while the contribution due to scatter is strongest at the center and drops off abruptly at the outer radius. An analytic function incorporating these features was fit to Monte Carlo results determined for infinite polyethylene cylinders of various diameters. A further feature of this function is that it is integrable. Results: Symmetry and continuity dictate a local extremum at the center which is a minimum for the larger sizes. The competing effects described above can Resultin an absolute maximum occurring between the center and outer edge of the cylinders. For the smallest cylinders, the maximum dose may occur at the center. Conclusion: An integrable, analytic function can be used to characterize the radial dependency of dose for cylindrical CT phantoms of various sizes. One use for this is to help determine average dose distribution over the central cylinder plane when equilibrium dose has been reached.

Time-Dependent Toxic and Genotoxic Effects of Zinc Oxide Nanoparticles after Long-Term and Repetitive Exposure to Human Mesenchymal Stem Cells

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Pascal Ickrath

2017-12-01

Full Text Available Zinc oxide nanoparticles (ZnO-NP are widely spread in consumer products. Data about the toxicological characteristics of ZnO-NP is still under controversial discussion. The human skin is the most important organ concerning ZnO-NP exposure. Intact skin was demonstrated to be a sufficient barrier against NPs; however, defect skin may allow NP contact to proliferating cells. Within these cells, stem cells are the most important toxicological target for NPs. The aim of this study was to evaluate the genotoxic and cytotoxic effects of ZnO-NP at low-dose concentrations after long-term and repetitive exposure to human mesenchymal stem cells (hMSC. Cytotoxic effects of ZnO-NP were measured by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT assay. Furthermore, genotoxicity was evaluated by the comet assay. For long-term observation over 6 weeks, transmission electron microscopy (TEM was applied. The results of the study indicated cytotoxic effects of ZnO-NP beginning at high concentrations of 50 μg/mL and genotoxic effects in hMSC exposed to 1 and 10 μg/mL ZnO-NP. Repetitive exposure enhanced cyto- but not genotoxicity. Intracellular NP accumulation was observed up to 6 weeks. The results suggest cytotoxic and genotoxic potential of ZnO-NP. Even low doses of ZnO-NP may induce toxic effects as a result of repetitive exposure and long-term cellular accumulation. This data should be considered before using ZnO-NP on damaged skin.

Late protein synthesis-dependent phases in CTA long-term memory: BDNF requirement

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Araceli eMartínez-Moreno

2011-09-01

Full Text Available It has been proposed that long-term memory persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related long-term memory when protein synthesis was inhibited. Our previous studies on the insular cortex (IC, a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA, have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis dependent in different time-windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 hours after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes.

The acute and long-term neurotoxic effects of MDMA on marble burying behaviour in mice.

Science.gov (United States)

Saadat, Kathryn S; Elliott, J Martin; Colado, M Isabel; Green, A Richard

2006-03-01

When mice are exposed to harmless objects such as marbles in their cage they bury them, a behaviour sometimes known as defensive burying. We investigated the effect of an acute dose of MDMA (èecstasy') and other psychoactive drugs on marble burying and also examined the effect of a prior neurotoxic dose of MDMA or p-chloroamphetamine (PCA) on burying. Acute administration of MDMA produced dose-dependent inhibition of marble burying (EC50: 7.6 micro mol/kg). Other drugs that enhance monoamine function also produced dose-dependent inhibition: methamphetamine PCA paroxetine MDMA GBR 12909 methylphenidate. None of these drugs altered locomotor activity at a dose that inhibited burying. A prior neurotoxic dose of MDMA, which decreased striatal dopamine content by 60%, but left striatal 5-HT content unaltered, did not alter spontaneous marble burying 18 or 40 days later. However, a neurotoxic dose of PCA which decreased striatal dopamine by 60% and striatal 5-HT by 70% attenuated marble burying 28 days later. Overall, these data suggest that MDMA, primarily by acutely increasing 5-HT function, acts like several anxiolytic drugs in this behavioural model. Long-term loss of cerebral 5-HT content also produced a similar effect. Since this change was observed only after 28 days, it is probably due to an adaptive response in the brain.

Long-term Conventionally Dosed Vancomycin Therapy In Patients With Orthopaedic Implant-related Infections Seems As Effective And Safe As Long-term Penicillin Or Clindamycin Therapy. A Retrospective Cohort Study Of 103 Patients.

Science.gov (United States)

Aleman, Jacomien; Moojen, Dirk Jan F; van Ogtrop, Marc L; Poolman, Rudolf W; Franssen, Eric J F

2018-01-01

Objectives : Antimicrobial therapy is one of the cornerstones of orthopaedic implant-related infections (OIRI) treatment. Infections with Gram-positive bacteria are often treated with vancomycin, penicillin or clindamycin. A recent IDSA guideline suggests increasing the dose of vancomycin to increase the trough vancomycin target serum concentrations. This is deemed necessary because of an observed decrease in vancomycin susceptibility among Gram-positive bacteria. However, elevated vancomycin concentrations are correlated with the risk of nephrotoxicity, especially with prolonged therapy. Compared to most countries, rates of resistance against antibiotics among bacteria in the Netherlands are lower for currently available antibiotics, therefore lower target concentrations of vancomycin are probably efficacious for the treatment of infections. In this study we evaluated the efficacy and safety of long-term conventionally dosed vancomycin therapy, as an initial therapy for OIRI, and compared this with long-term penicillin and clindamycin therapy, as initial therapy, in patients with Gram-positive orthopaedic implant-related infections. Methods : A retrospective, observational study was conducted in 103 adult patients treated for OIRI, with vancomycin, penicillin or clindamycin for at least 10 days. The target trough serum concentration of vancomycin was 10-15 mg/l. Results : 74% of our patients were treated successfully with vancomycin, as initial therapy, (no reinfection within 1 year) versus 55% of our patients treated with either an antibiotic of the penicillin class (mostly flucloxacillin) or clindamycin (p=0.08), as initial therapy. For patients treated with vancomycin we observed a serum creatinine increase of 6 μmol/l, for patients treated with either an antibiotic of the penicillin class or clindamycin the serum creatinine increase was 4 μmol/l (p=0.395). Conclusions : In our population of patients with OIRI long-term treatment with conventionally dosed

Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement

OpenAIRE

Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F.; Escobar, Martha L.

2011-01-01

It has been proposed that long-term memory persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related long-term memo...

Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats.

Science.gov (United States)

Favaro, Vanessa Manchim; Yonamine, Maurício; Soares, Juliana Carlota Kramer; Oliveira, Maria Gabriela Menezes

2015-01-01

Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT) from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs) induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM), fear conditioning and elevated plus maze (EPM) performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.

Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats.

Directory of Open Access Journals (Sweden)

Vanessa Manchim Favaro

Full Text Available Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM, fear conditioning and elevated plus maze (EPM performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.

Testing for long-range dependence in the Brazilian term structure of interest rates

International Nuclear Information System (INIS)

Cajueiro, Daniel O.; Tabak, Benjamin M.

2009-01-01

This paper presents empirical evidence of fractional dynamics in interest rates for different maturities for Brazil. A variation of a newly developed test for long-range dependence, the V/S statistic, with a post-blackening bootstrap is employed. Results suggest that Brazilian interest rates possess strong long-range dependence in volatility, even when considering the structural break in 1999. These findings imply that the development of policy models that give rise to long-range dependence in interest rates' volatility could be very useful. The long-short-term interest rates spread has strong long-range dependence, which suggests that traditional tests of expectation hypothesis of the term structure of interest rates may be misspecified.

Effectiveness and tolerance of long-term malaria prophylaxis with mefloquine. Need for a better dosing regimen.

Science.gov (United States)

Lobel, H O; Bernard, K W; Williams, S L; Hightower, A W; Patchen, L C; Campbell, C C

1991-01-16

To measure the effectiveness and tolerance of long-term malaria prophylaxis with mefloquine, the incidence of Plasmodium falciparum malaria and of adverse reactions was compared in Peace Corps volunteers in West Africa who took mefloquine every 2 weeks and in volunteers who took chloroquine phosphate weekly. Mefloquine was only 63% more effective than chloroquine; the monthly incidence of P falciparum infections was one case per 100 volunteers who took mefloquine and 2.7 cases per 100 volunteers who took chloroquine. Using daily proguanil (chloroguanide) hydrochloride in addition to chloroquine did not provide additional protection. All mefloquine prophylaxis failures occurred during the second week of the every-2-weeks dosing regimen in volunteers who had used mefloquine for more than 2 months. Blood concentrations of mefloquine were lower during the second week of the alternate-week regimen than during the first week, suggesting that blood levels are too low during the second week to suppress parasitemia. No serious adverse reactions were observed. The results indicate that a dosing regimen of 250 mg of mefloquine weekly should be considered for travelers to areas with chloroquine-resistant P falciparum malaria.

Microclimatic effects on outdoor radon and its progeny in a long-term study

International Nuclear Information System (INIS)

Schuetz, M.; Keller, G.; Kappel, R.J.A.

1994-01-01

The dose due to the long term radon exposure is estimated from the radon concentration and from an equilibrium factor that in the literature is reported with a wide uncertainty. Therefore the radon equilibrium factor outdoors and its dependence on climatic effects should be investigated in a long-term study. Both the outdoor concentrations of radon and of its progeny near Ellweiler/Hunsrueck were measured continuously during 12 months and the resulting equilibrium factors were determined. Simultaneously to the every 2 hour's radon data many meterological parameters as temperature and relative to humidity of the air, barometric pressure and duration and amount of rainfall were recorded. At a height of 6 meters above ground and in 10 minute intervals the local wind direction and velocity were registered. By that a set of more than 3000 single measurements of the equilibrium factor and of the corresponding weather conditions was collected

Combined management of retroperitoneal sarcoma with dose intensification radiotherapy and resection: Long-term results of a prospective trial.

LENUS (Irish Health Repository)

Smith, Myles J F

2014-01-07

Late failure is a challenging problem following resection of retroperitoneal sarcoma (RPS). We investigated the effects of preoperative XRT plus dose escalation with early postoperative brachytherapy (BT) on long-term survival and recurrence in RPS.

Immunomodulatory effect of ganoderma lucidum polysaccharides (GLP) on long-term heavy-load exercising mice.

Science.gov (United States)

Shi, Yali; Cai, Dehua; Wang, Xiaojie; Liu, Xinshen

2012-12-01

Long-term heavy-load exercise can lead to a decrease in the organism's immune response. In this study, we used 100 Kunming (KM) mice to investigate the immune-regulatory effects of Ganoderma lucidum polysaccharides (GLP) on long-term heavy-load exercising mice. Peripheral white blood cells (WBC), the absolute value of neutrophils (NEUT), the phagocytic function of macrophages, serum agglutination valence, and the number of plaque-forming cells (PFC) were evaluated 4 weeks after gavaging long-term heavy-load exercising mice with GLP. After exercise, the WBC count in peripheral blood, absolute neutrophil count, macrophage phagocytic index, serum agglutination valence, and the number of plaque-forming cells were significantly reduced in the mice not fed GLP. Both medium and high doses of GLP drastically increased peripheral WBC, absolute neutrophil count, macrophage phagocytic index, serum agglutination valence, and the number of plaque-forming cells in long-term heavy-load exercising mice. High doses of GLP increased peritoneal macrophage phagocytic rate considerably. With this study, we demonstrate that 4 weeks of heavy-load exercise can lead to exercise-induced immunosuppression in mice. A supplement of GLP fed to these mice improves both non-specific and specific immune responses among these mice. The effect for the high-dose GLP treatment is especially significant.

Study on the estimation of probabilistic effective dose. Committed effective dose from intake of marine products using Oceanic General Circulation Model

International Nuclear Information System (INIS)

Nakano, Masanao

2007-01-01

The worldwide environmental protection is required by the public. A long-term environmental assessment from nuclear fuel cycle facilities to the aquatic environment also becomes more important to utilize nuclear energy more efficiently. Evaluation of long-term risk including not only in Japan but also in neighboring countries is considered to be necessary in order to develop nuclear power industry. The author successfully simulated the distribution of radionuclides in seawater and seabed sediment produced by atmospheric nuclear tests using LAMER (Long-term Assessment ModEl for Radioactivity in the oceans). A part of the LAMER calculated the advection- diffusion-scavenging processes for radionuclides in the oceans and the Japan Sea in cooperate with Oceanic General Circulation Model (OGCM) and was validated. The author is challenging to calculate probabilistic effective dose suggested by ICRP from intake of marine products due to atmospheric nuclear tests using the Monte Carlo method in the other part of LAMER. Depending on the deviation of each parameter, the 95th percentile of the probabilistic effective dose was calculated about half of the 95th percentile of the deterministic effective dose in proforma calculation. The probabilistic assessment gives realistic value for the dose assessment of a nuclear fuel cycle facility. (author)

Long term neurocognitive impact of low dose prenatal methylmercury exposure in Hong Kong.

Science.gov (United States)

Lam, Hugh Simon; Kwok, Ka Ming; Chan, Peggy Hiu Ying; So, Hung Kwan; Li, Albert Martin; Ng, Pak Cheung; Fok, Tai Fai

2013-04-01

International studies suggest that low dose prenatal methylmercury exposure (>29 nmol/L) has long-term adverse neurocognitive effects. There is evidence that the majority of children in Hong Kong exceed this level as a result of high fish consumption of mothers during pregnancy. To study whether there are any associations between low-dose prenatal methylmercury exposure and neurocognitive outcomes in Hong Kong children. All 1057 children from the original birth cohort were eligible for entry into the study, except children with conditions that would affect neurocognitive development, but were unrelated to methylmercury exposure. Subjects were assessed by a wide panel of tests covering a broad range of neurocognitive functions: Hong Kong Wechsler Intelligence Scale for Children (HK-WISC), Hong Kong List Learning Test (HKLLT), Tests of Everyday Attention for Children (TEACH), Boston Naming Test, and Grooved Pegboard Test. 608 subjects were recruited (median age 8.2 years, IQR 7.3, 8.8; 53.9% boys). After correction by confounders including child age and sex, multivariate analysis showed that cord blood mercury concentration was significantly associated with three subtests: Picture Arrangement of HK-WISC (coefficient -0.944, P=0.049) and Short and Long Delay Recall Difference of the HKLLT (coefficient -1.087, P=0.007 and coefficient -1.161, P=0.005, respectively), i.e., performance worsened with increasing prenatal methylmercury exposure in these subtests. Small, but statistically significant adverse associations between prenatal methylmercury exposure and long-term neurocognitive effects (a visual sequencing task and retention ability of verbal memory) were found in our study. These effects are compatible with findings of studies with higher prenatal methylmercury exposure levels and suggest that safe strategies to further reduce exposure levels in Hong Kong are desirable. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hematopoietic effects of early and long terms of rhG-CSF in mice exposed to 6.5 Gy irradiation

International Nuclear Information System (INIS)

Cong Yuwen; Mao Bingzhi; Luo Qingliang; Dong Bo; Chen Huipeng

1996-01-01

In order to evaluate the long-term protective effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on hematopoiesis after a second irradiation, different doses of rhG-CSF were given to 6.5 Gy 60 Co γ-ray irradiated C 57 BL/6 mice. When the peripheral blood cells recovered to normal level, the survived mice were exposed to a second dose of radiation exactly the same as the first one. It was showed that peripheral WBC, RBC and platelet counts recovered much quicker in the mice treated with the factor after irradiation and the effect was dependent on the dose of rhG-CSF. In the survived mice exposed to a second dose of γ-rays 45 days after the first irradiation, as compared with the control, the recovery of peripheral blood cell counts was evidently accelerated and the survival rate was markedly elevated. These results not only demonstrate that the recovery of hematopoiesis in the irradiated mice could be accelerated after the administration of rhG-CSF but also suggest that early administration of the factor could produce a long-term protective effect on the hematopoietic function against a second irradiation given 45 days later

Long-term prognostic performance of low-dose coronary computed tomography angiography with prospective electrocardiogram triggering

Energy Technology Data Exchange (ETDEWEB)

Clerc, Olivier F.; Kaufmann, Basil P.; Possner, Mathias; Liga, Riccardo; Vontobel, Jan; Mikulicic, Fran; Graeni, Christoph; Benz, Dominik C.; Fuchs, Tobias A.; Stehli, Julia; Pazhenkottil, Aju P.; Gaemperli, Oliver; Kaufmann, Philipp A.; Buechel, Ronny R. [University Hospital Zurich, Cardiac Imaging, Department of Nuclear Medicine, Zurich (Switzerland)

2017-11-15

To assess long-term prognosis after low-dose 64-slice coronary computed tomography angiography (CCTA) using prospective electrocardiogram-triggering. We included 434 consecutive patients with suspected or known coronary artery disease referred for low-dose CCTA. Patients were classified as normal, with non-obstructive or obstructive lesions, or previously revascularized. Coronary artery calcium score (CACS) was assessed in 223 patients. Follow-up was obtained regarding major adverse cardiac events (MACE): cardiac death, myocardial infarction and elective revascularization. We performed Kaplan-Meier analysis and Cox regressions. Mean effective radiation dose was 1.7 ± 0.6 mSv. At baseline, 38% of patients had normal arteries, 21% non-obstructive lesions, 32% obstructive stenosis and 8% were revascularized. Twenty-nine patients (7%) were lost to follow-up. After a median follow-up of 6.1 ± 0.6 years, MACE occurred in 0% of patients with normal arteries, 6% with non-obstructive lesions, 30% with obstructive stenosis and 39% of those revascularized. MACE occurrence increased with increasing CACS (P < 0.001), but 4% of patients with CACS = 0 experienced MACE. Multivariate Cox regression identified obstructive stenosis, lesion burden in CCTA and CACS as independent MACE predictors (P ≤ 0.001). Low-dose CCTA with prospective electrocardiogram-triggering has an excellent long-term prognostic performance with a warranty period >6 years for patients with normal coronary arteries. (orig.)

Long-term prognostic performance of low-dose coronary computed tomography angiography with prospective electrocardiogram triggering

International Nuclear Information System (INIS)

Clerc, Olivier F.; Kaufmann, Basil P.; Possner, Mathias; Liga, Riccardo; Vontobel, Jan; Mikulicic, Fran; Graeni, Christoph; Benz, Dominik C.; Fuchs, Tobias A.; Stehli, Julia; Pazhenkottil, Aju P.; Gaemperli, Oliver; Kaufmann, Philipp A.; Buechel, Ronny R.

2017-01-01

To assess long-term prognosis after low-dose 64-slice coronary computed tomography angiography (CCTA) using prospective electrocardiogram-triggering. We included 434 consecutive patients with suspected or known coronary artery disease referred for low-dose CCTA. Patients were classified as normal, with non-obstructive or obstructive lesions, or previously revascularized. Coronary artery calcium score (CACS) was assessed in 223 patients. Follow-up was obtained regarding major adverse cardiac events (MACE): cardiac death, myocardial infarction and elective revascularization. We performed Kaplan-Meier analysis and Cox regressions. Mean effective radiation dose was 1.7 ± 0.6 mSv. At baseline, 38% of patients had normal arteries, 21% non-obstructive lesions, 32% obstructive stenosis and 8% were revascularized. Twenty-nine patients (7%) were lost to follow-up. After a median follow-up of 6.1 ± 0.6 years, MACE occurred in 0% of patients with normal arteries, 6% with non-obstructive lesions, 30% with obstructive stenosis and 39% of those revascularized. MACE occurrence increased with increasing CACS (P < 0.001), but 4% of patients with CACS = 0 experienced MACE. Multivariate Cox regression identified obstructive stenosis, lesion burden in CCTA and CACS as independent MACE predictors (P ≤ 0.001). Low-dose CCTA with prospective electrocardiogram-triggering has an excellent long-term prognostic performance with a warranty period >6 years for patients with normal coronary arteries. (orig.)

Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.

Science.gov (United States)

Studerus, Erich; Kometer, Michael; Hasler, Felix; Vollenweider, Franz X

2011-11-01

Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

Learning-dependent neurogenesis in the olfactory bulb determines long-term olfactory memory.

Science.gov (United States)

Sultan, S; Mandairon, N; Kermen, F; Garcia, S; Sacquet, J; Didier, A

2010-07-01

Inhibitory interneurons of the olfactory bulb are subjected to permanent adult neurogenesis. Their number is modulated by learning, suggesting that they could play a role in plastic changes of the bulbar network associated with olfactory memory. Adult male C57BL/6 mice were trained in an associative olfactory task, and we analyzed long-term retention of the task 5, 30, and 90 d post-training. In parallel, we assessed the fate of these newborn cells, mapped their distribution in the olfactory bulb and measured their functional implication using the immediate early gene Zif268. In a second set of experiments, we pharmacologically modulated glutamatergic transmission and using the same behavioral task assessed the consequences on memory retention and neurogenesis. Finally, by local infusion of an antimitotic drug, we selectively blocked neurogenesis during acquisition of the task and looked at the effects on memory retention. First we demonstrated that retrieval of an associative olfactory task recruits the newborn neurons in odor-specific areas of the olfactory bulb selected to survive during acquisition of the task and that it does this in a manner that depends on the strength of learning. We then demonstrated that acquisition is not dependent on neurogenesis if long-term retention of the task is abolished by blocking neurogenesis. Adult-born neurons are thus involved in changes in the neural representation of an odor; this underlies long-term olfactory memory as the strength of learning is linked to the duration of this memory. Neurogenesis thus plays a crucial role in long-term olfactory memory.

Effect of long term intake of aspartame on antioxidant defense status in liver.

Science.gov (United States)

Abhilash, M; Paul, M V Sauganth; Varghese, Mathews V; Nair, R Harikumaran

2011-06-01

The present study evaluates the effect of long term intake of aspartame, the artificial sweetener, on liver antioxidant system and hepatocellular injury in animal model. Eighteen adult male Wistar rats, weighing 150-175 g, were randomly divided into three groups as follows: first group was given aspartame dissolved in water in a dose of 500 mg/kg b.wt.; the second group was given a dose of 1000 mg/kg b.wt.; and controls were given water freely. Rats that had received aspartame (1000 mg/kg b.wt.) in the drinking water for 180 days showed a significant increase in activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT). The concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx), and glutathione reductase (GR) were significantly reduced in the liver of rats that had received aspartame (1000 mg/kg b.wt.). Glutathione was significantly decreased in both the experimental groups. Histopathological examination revealed leukocyte infiltration in aspartame-treated rats (1000 mg/kg b.wt.). It can be concluded from these observations that long term consumption of aspartame leads to hepatocellular injury and alterations in liver antioxidant status mainly through glutathione dependent system. Copyright © 2011 Elsevier Ltd. All rights reserved.

A comparison of the angular dependence of effective dose and effective dose equivalent

International Nuclear Information System (INIS)

Sitek, M.A.; Gierga, D.P.; Xu, X.G.

1996-01-01

In ICRP (International Commission on Radiological Protection) Publication 60, the set of critical organs and their weighing factors were changed, defining the quantity effective dose, E. This quantity replaced the effective dose equivalent, H E , as defined by ICRP 26. Most notably, the esophagus was added to the list of critical organs. The Monte Carlo neutron/photon transport code MCNP was used to determine the effective dose to sex-specific anthropomorphic phantoms. The phantoms, developed in previous research, were modified to include the esophagus. Monte Carlo simulations were performed for monoenergetic photon beams of energies 0.08 MeV, 0.3 MeV, and 1.0 MeV for various azimuthal and polar angles. Separate organ equivalent doses were determined for male and female phantoms. The resulting organ equivalent doses were calculated from arithmetic mean averages. The angular dependence of effective dose was compared with that of effective dose equivalent reported in previous research. The differences between the two definitions and possible implications to regulatory agencies were summarized

The Fukushima nuclear accident and the pale grass blue butterfly: evaluating biological effects of long-term low-dose exposures.

Science.gov (United States)

Hiyama, Atsuki; Nohara, Chiyo; Taira, Wataru; Kinjo, Seira; Iwata, Masaki; Otaki, Joji M

2013-08-12

On August 9th 2012, we published an original research article in Scientific Reports, concluding that artificial radionuclides released from the Fukushima Dai-ichi Nuclear Power Plant exerted genetically and physiologically adverse effects on the pale grass blue butterfly Zizeeria maha in the Fukushima area. Immediately following publication, many questions and comments were generated from all over the world. Here, we have clarified points made in the original paper and answered questions posed by the readers. The following points were clarified. (1) There are many advantages to using the pale grass blue butterfly as an indicator species. (2) The forewings of the individuals collected in Fukushima were significantly smaller than in the northern and southern localities. (3) We observed growth retardation in the butterflies from the Fukushima area. (4) The aberrant colour patterns in the butterflies obtained in the Fukushima area were different from the colour patterns induced by temperature and sibling crosses but similar to those induced by external and internal exposures to the artificial radionuclides and by a chemical mutagen, suggesting that genetic mutations caused the aberrations. (5) This species of butterfly has been plentiful in Fukushima area for at least half a century. We here present specimens collected from Fukushima Prefecture before the accident. (6) Mutation accumulation was detected by the increase in the abnormality rates from May 2011 to September 2011. (7) The abnormal traits were heritable. (8) Our sampling localities were not affected by the tsunami. (9) We used a high enough number of samples to obtain statistically significant results. (10) The standard rearing method was followed, producing normal adults in the control groups. (11) The exposure experiments successfully reproduced the results of the field work. This species of butterfly is vulnerable to long-term low-dose internal and external exposures; however, insect cells are known to be

Recovery of the proliferative and functional integrity of mouse bone marrow in long-term cultures established after whole-body irradiation at different doses and dose rates

International Nuclear Information System (INIS)

Bierkens, J.G.; Hendry, J.H.; Testa, N.G.

1991-01-01

Injury inflicted upon the bone marrow stroma following whole-body irradiation and its repair over a 1-year period has been assessed in murine long-term bone marrow cultures established at increasing time intervals after irradiation. Different doses at different dose rates (10 Gy at 0.05 cGy/min, 4.5 Gy and 10 Gy at 1.6 cGy/min, and 4 x 4.5 Gy [3 weeks between doses] at 60 cGy/min) were chosen so as to maximize differences in effect in the stroma. The cellularity of the adherent layer in long-term cultures established 1 month after irradiation was reduced by 40%-90% depending on the dose and dose rate. Simultaneous with the poor ability of the marrow to form adherent layers, the cumulative spleen colony-forming unit (CFU-S) and granulocyte-macrophage colony-forming cell (GM-CFC) production over a 7-week period was reduced to 0% and 30% of control cultures, respectively. The slow recovery of the adherent layer was paralleled by an increase in the numbers of CFU-S and GM-CFC in the supernatant. Cultures established from repeatedly irradiated mice performed poorly over the entire 1-year period. Whereas the regeneration of the stroma was near complete 1 year after irradiation, the CFU-S and GM-CFC levels reached only between 50% and 80% of control cultures, respectively. Also, the concentration of CFU-S and GM-CFC in the supernatant remained persistently lower in cultures established from irradiated mice as compared to control cultures. The levels of sulfated glycosaminoglycans, which have been implicated in the establishment of the functional integrity of the microenvironment, were not reduced in the adherent layers at any time after irradiation. These results indicate that the regeneration of the stroma is accompanied by an incomplete recovery of active hemopoiesis in vitro

The relationships between radiation doses and their effects

International Nuclear Information System (INIS)

Beau, P.G.; Nenot, J.C.

1982-01-01

Dose-effect relationships have been developed both for the biological effects studied by Radiobiology and the long-term pathological effects (malignant diseases) studied by Radiation Protection. The former approach chiefly considers the primary biological injuries at the cellular level, and the relationship between the dependent variable characteristic of the effect and the dose -an independent variable- has an explanatory meaning. The parameters associated to the independent variable have a biophysical signification and fit into a model of the action of ionizing radiations. In the latter approach, the relationship is pragmatic and the previous parameters are just the results of a curve-fitting procedure realized on experimental or human data. The biophysical models have led to a general formulation associating a linear term to a quadratic term both of them weighted by an exponential term describing cellular killing at the highest doses. To a certain extent the curves obtained for leukemias, bronchopulmonary and breast cancers prove the validity of the pragmatic model [fr

Neuroprotective effect of interleukin-6 regulation of voltage-gated Na+ channels of cortical neurons is time- and dose-dependent

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Wei Xia

2015-01-01

Full Text Available Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour exposure of interleukin-6 on cortical neurons at various concentrations (0.1, 1, 5 and 10 ng/mL and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations (2, 4, 8, 24 and 48 hours by studying voltage-gated Na + channels using a patch-clamp technique. Voltage-clamp recording results demonstrated that interleukin-6 suppressed Na + currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na + channels in rat cortical neurons by interleukin-6 is time- and dose-dependent.

Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement

Science.gov (United States)

Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F.; Escobar, Martha L.

2011-01-01

It has been proposed that long-term memory (LTM) persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related LTM when protein synthesis was inhibited. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis-dependent in different time windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 h after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side) in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes. PMID:21960964

Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement.

Science.gov (United States)

Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F; Escobar, Martha L

2011-01-01

It has been proposed that long-term memory (LTM) persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related LTM when protein synthesis was inhibited. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis-dependent in different time windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 h after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side) in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes.

Radiolytic gas production during long-term storage of nuclear wastes

International Nuclear Information System (INIS)

Bibler, N.E.

1976-01-01

Gases produced by in situ radiolysis of sealed solidified nuclear wastes during long-term storage could conceivably breach containment. Therefore, candidate waste forms (matrices containing simulated nuclear wastes) were irradiated with 60 Co-γ and 244 Cm-α radiation. These forms were: cement containing simulated fission product sludges, vermiculite containing organic liquids, and cellulosics contaminated with α-emitting transuranic isotopes. For cement waste forms exposed to γ-radiolysis, an equilibrium hydrogen pressure was reached that was dose rate dependent. For α-radiolysis, equilibrium was not reached. With organic wastes (n-octane on vermiculite), H 2 and traces of CO 2 and CH 4 were produced, and O 2 was consumed with both radiations. Only energy absorbed by the organic material was effective in producing H 2 . At low dose rates with both α- and γ-irradiations, G(H 2 ) was 4.5 and G(-O 2 ) was 5.0. Also, equilibrium was not obtained. For cellulosic material, H 2 , CO 2 , and CO were produced in the ratio of 1.0:0.7:0.3, and O 2 was consumed. With α-radiolysis, G(gas) was dose dependent; measured values ranged from 2.2 to 0.6 as the dose increased. Implications of all these results on long-term storage of radioactive waste are discussed. Some data from an actual nuclear wasteform are also presented

Reaction of the hematopoietic system under long-term emotional stress developed after preliminary gamma-irradiation with low doses

International Nuclear Information System (INIS)

Moroz, B.B.; Deshevoj, Yu.B.; Lebedev, V.G.; Lyrshchikova, A.V.; Vorotnikova, T.V.

1997-01-01

In experiments on rats and mice it was shown that the preliminary protected gamma-irradiation with cumulative dose of 0.9 Gy (dose rate - 0.03 Gy/day) or single short-term gamma-irradiation with dose of 0.9 Gy (dose rate - 1.61 Gy/min) inhibited development of adaptive reactions and compensatory abilities of the hematopoietic system under long-term emotional stress

Oil use and oil dependency: Long-term issues

International Nuclear Information System (INIS)

Serot, D.E.; Belzer, D.B.; Guthrie, S.A.; Roop, J.M.

1989-06-01

The continued dependence of the United States on imported oil is a matter of increasing concern. Under the direction of the Department of Energy's Office of Policy Integration, Pacific Northwest Laboratory conducted a study which was to examine long-term issues related to oil dependence. Major issues addressed are (1) energy efficiency and the role of new technologies, (2) fuel switching, and (3) regional factors affecting fuel use. The study examines all major end-use sectors in the economy, covering the industrial, commercial, residential, transportation, and electric utility sectors. The potential impacts of efficiency improvements in oil- using equipment are assessed through the year 2000. 107 refs., 8 figs., 9 tabs

Time-Dependent Global Sensitivity Analysis for Long-Term Degeneracy Model Using Polynomial Chaos

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Jianbin Guo

2014-07-01

Full Text Available Global sensitivity is used to quantify the influence of uncertain model inputs on the output variability of static models in general. However, very few approaches can be applied for the sensitivity analysis of long-term degeneracy models, as far as time-dependent reliability is concerned. The reason is that the static sensitivity may not reflect the completed sensitivity during the entire life circle. This paper presents time-dependent global sensitivity analysis for long-term degeneracy models based on polynomial chaos expansion (PCE. Sobol’ indices are employed as the time-dependent global sensitivity since they provide accurate information on the selected uncertain inputs. In order to compute Sobol’ indices more efficiently, this paper proposes a moving least squares (MLS method to obtain the time-dependent PCE coefficients with acceptable simulation effort. Then Sobol’ indices can be calculated analytically as a postprocessing of the time-dependent PCE coefficients with almost no additional cost. A test case is used to show how to conduct the proposed method, then this approach is applied to an engineering case, and the time-dependent global sensitivity is obtained for the long-term degeneracy mechanism model.

Dose dependence on stochastic radiobiological effect in radiation risk estimation

International Nuclear Information System (INIS)

Komochkov, M.M.

1999-01-01

The analysis of the results in dose -- effect relationship observation has been carried out on the cell and organism levels, with the aim to obtain more precise data on the risk coefficients at low doses. The results are represented by two contrasting groups of dose dependence on effect: a downwards concave and a J-shaped curve. Both types of dependence are described by the equation solutions of an assumed unified protective mechanism, which comprises two components: constitutive and adaptive or inducible ones. The latest data analysis of the downwards concave dependence curves shows a considerable underestimation of radiation risk in all types of cancer, except leukemia, for a number of critical groups in a population, at low doses comparing to the ICRP recommendations. With the dose increase, the decrease of the effect value per dose unit is observed. It may be possibly related to the switching of the activity of the adaptive protective mechanism, with some threshold dose values being exceeded

An Improved Methodology of Monetary Values of the Unit Collective Dose for Intervention Against Long-Term Exposure Following a Nuclear Accident

International Nuclear Information System (INIS)

Hwang, Won Tae; Kim, Eun Han; Suh, Kyung Suk; Choi, Young Gil; Han, Moon Hee

2002-01-01

A more practice approach for the determination of monetary values of the unit collective dose for intervention against long-term exposure following a nuclear accident was proposed. In addition, the monetary values of the unit collective dose estimated from the proposed approach were compared with those estimated from the previous model, which are derived from assumptions of routine exposure and the same values are applied in a nuclear accident without modification, using Korea economic data. The monetary values based on the proposed approach showed a distinct difference depending on inequity in the distribution of individual doses. The discounting rate was also an important factor in determination of monetary values of the unit collective dose

An Improved Methodology of Monetary Values of the Unit Collective Dose for Intervention Against Long-Term Exposure Following a Nuclear Accident

Energy Technology Data Exchange (ETDEWEB)

Hwang, Won Tae; Kim, Eun Han; Suh, Kyung Suk; Choi, Young Gil; Han, Moon Hee [KAERI, Daejeon (Korea, Republic of)

2002-06-15

A more practice approach for the determination of monetary values of the unit collective dose for intervention against long-term exposure following a nuclear accident was proposed. In addition, the monetary values of the unit collective dose estimated from the proposed approach were compared with those estimated from the previous model, which are derived from assumptions of routine exposure and the same values are applied in a nuclear accident without modification, using Korea economic data. The monetary values based on the proposed approach showed a distinct difference depending on inequity in the distribution of individual doses. The discounting rate was also an important factor in determination of monetary values of the unit collective dose.

Toxicological Effects of Caco-2 Cells Following Short-Term and Long-Term Exposure to Ag Nanoparticles

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Ni Chen

2016-06-01

Full Text Available Extensive utilization increases the exposure of humans to Ag nanoparticles (NPs via the oral pathway. To comprehensively address the action of Ag NPs to the gastrointestinal systems in real situations, i.e., the long-term low-dose exposure, we evaluated and compared the toxicity of three Ag NPs (20–30 nm with different surface coatings to the human intestine cell Caco-2 after 1-day and 21-day exposures, using various biological assays. In both the short- and long-term exposures, the variety of surface coating predominated the toxicity of Ag NPs in a descending order of citrate-coated Ag NP (Ag-CIT, bare Ag NP (Ag-B, and poly (N-vinyl-2-pyrrolidone-coated Ag NP (Ag-PVP. The short-term exposure induced cell growth inhibition and death. The cell viability loss appeared after cells were exposed to 0.7 μg/mL Ag-CIT, 0.9 μg/mL Ag-B or >1.0 μg/mL Ag-PVP for 24 h. The short-term and higher-dose exposure also induced reactive oxygen species (ROS generation, mitochondrial damage, cell membrane leakage, apoptosis, and inflammation (IL-8 level. The long-term exposure only inhibited the cell proliferation. After 21-day exposure to 0.4 μg/mL Ag-CIT, the cell viability dropped to less than 50%, while cells exposed to 0.5 μg/mL Ag-PVP remained normal as the control. Generally, 0.3 μg/mL is the non-toxic dose for the long-term exposure of Caco-2 cells to Ag NPs in this study. However, cells presented inflammation after exposure to Ag NPs with the non-toxic dose in the long-term exposure.

Efficacy of modest dose irradiation in combination with long-term endocrinal treatment for high-risk prostate cancer. A preliminary report

International Nuclear Information System (INIS)

Sasaki, Tomonari; Nakamura, Katsumasa; Shioyama, Yoshiyuki

2004-01-01

Although radiotherapy in combination with endocrinal manipulation has been identified as an effective treatment for patients with high-risk prostate cancer, the optimal dose for locoregional control of prostate cancer in combination with hormonal therapy has not yet been determined. The efficacy of modest doses of irradiation (60-62 Gy) combined with long-term endocrinal treatment for patients with high-risk prostate cancer (defined as a pretreatment prostate-specific antigen (PSA) level greater than 20 ng/ml or a Gleason's score of 8-10 or T3-T4 disease) was analyzed in 60 Japanese patients. The patients included in this study had received radical radiotherapy with long-term endocrinal manipulation in the period between 1993 and 2000. The median age of the patients was 70 years (range, 56-83). Neoadjuvant hormonal therapy with a median duration of 3.9 months was performed prior to radiotherapy, and hormonal therapy was continued until recurrence. A median dose of 61.4 Gy (range, 44-71.4) was delivered to the prostate. Pelvic node irradiation was performed in 49 patients (81.6%). After a median follow-up period of 28.5 months, the overall survival, cause-specific survival and biochemical relapse-free survival at 3 years were 94.4%, 96% and 89.8%, respectively. Local failure was observed in one patient, distant metastases were observed in three patients and a late toxic effect greater than Grade 2 was not observed in any patients. This study, though preliminary due to a short-term follow-up period, reveals the possibility that modest doses of irradiation combined with long-term endocrinal treatment could be an effective means of achieving excellent local control of high-risk prostate cancer. (author)

Long-term biodosimetry Redux

International Nuclear Information System (INIS)

Simon, Steven L.; Bouville, Andre

2016-01-01

This paper revisits and reiterates the needs, purposes and requirements of bio-dosimetric assays for long-term dose and health risk assessments. While the most crucial need for bio-dosimetric assays is to guide medical response for radiation accidents, the value of such techniques for improving our understanding of radiation health risk by supporting epidemiological (long-term health risk) studies is significant. As new cohorts of exposed persons are identified and new health risk studies are undertaken with the hopes that studying the exposed will result in a deeper understanding of radiation risk, the value of reliable dose reconstruction is underscored. The ultimate application of biodosimetry in long-term health risk studies would be to completely replace model-based dose reconstruction-a complex suite of methods for retrospectively estimating dose that is commonly fraught with large uncertainties due to the absence of important exposure-related information, as well as imperfect models. While biodosimetry could potentially supplant model-based doses, there are numerous limitations of presently available techniques that constrain their widespread application in health risk research, including limited ability to assess doses received far in the past, high cost, great inter-individual variability, invasiveness, higher than preferred detection limits and the inability to assess internal dose (for the most part). These limitations prevent the extensive application of biodosimetry to large cohorts and should be considered a challenge to researchers to develop new and more flexible techniques that meet the demands of long-term health risk research. Events in recent years, e.g. the Fukushima reactor accident and the increased threat of nuclear terrorism, underscore that any event that results in significant radiation exposures of a group of people will also produce a much larger population, exposed at lower levels, but that likewise needs (or demands) an exposure

Long term population dose due to radon (Rn-222) released from uranium mill tailings

International Nuclear Information System (INIS)

Chambers, D.B.; Lower, L.M.; Stager, R.H.

2001-01-01

The results of a study undertaken by the European Commission on the external costs (environmental and social) of various energy production systems is likely to be influential in determining how the European Union will develop its energy supply systems. The estimated costs for nuclear power from the study will be based on the findings of the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), with the costs being dominated by the estimated long term (10,000 y) population doses due to radon (Rn-222) released from mill tailings. UNSCEAR developed a central estimate of 150 person-Sv per GW y and a range of 1 to 1,000 person-Sv per GW y. However, the generic data available to and being used by UNSCEAR are dated and are not appropriate for the current and planned future conditions in the uranium production industry, with the result that the estimated external costs of nuclear power (specifically, the doses due to radon emitted from mill tailings) are overestimated. The Uranium Institute sponsored a study to estimate long term population doses based on the most recent 1993 UNSCEAR methodology, but using data that would be more appropriate to the current major uranium production facilities. Site-specific information obtained from the owners/operators and the Uranium Institute included: present and proposed tailings management plans; tailings volumes and areas; ore grades and reserves; measurements and estimates of radon emission rates; and population densities. Tailings at closed facilities that no longer contribute to uranium production were not evaluated since it was assumed that these radon sources need not be considered in evaluating the external costs of current and future nuclear power production. Based on the same approach as UNSCEAR, but using a more sophisticated air dispersion model, and more site-specific data relative to existing sites and proposed tailings management practices, radon emission rates and population densities (that

Enhancement of long-term spatial memory in adult rats by the noncompetitive NMDA receptor antagonists, memantine and neramexane.

Science.gov (United States)

Zoladz, Phillip R; Campbell, Adam M; Park, Collin R; Schaefer, Daniela; Danysz, Wojciech; Diamond, David M

2006-10-01

Memantine and neramexane are noncompetitive NMDA receptor antagonists which have been investigated for their promising effects in aiding memory in people with dementia. Memantine is approved for the treatment of Alzheimer's disease, and neramexane is currently under development for this indication. Therefore, the present study provided a comparative assessment of the effects of equimolar doses of memantine and neramexane on spatial (hippocampus-dependent) memory. Adult male rats were given only 3 training trials to learn the location of a hidden platform in a water maze. In control (vehicle-injected) rats, this minimal amount of training produced intact short-term (15 min), but poor long-term (24 h), memory. Pre-training administration of memantine or neramexane produced a dose-dependent enhancement of long-term memory. Pharmacokinetic experiments with equimolar doses of both agents indicated that lower plasma levels of neramexane were more effective than memantine at enhancing memory. The effective doses of both agents in the current study produced plasma levels (and extrapolated brain CSF levels) within a range of activity at NMDA receptors and plasma levels seen in patients with Alzheimer's disease. These findings provide support for the use of neramexane as a pharmacological intervention in the treatment of dementia.

Sex-dependent long-term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats.

Science.gov (United States)

Lopez-Rodriguez, Ana Belen; Llorente-Berzal, Alvaro; Garcia-Segura, Luis M; Viveros, Maria-Paz

2014-03-01

Many young people consume ecstasy as a recreational drug and often in combination with cannabis. In this study, we aimed to mimic human consumption patterns and investigated, in male and female animals, the long-term effects of Δ(9) -tetrahydrocannabinol (THC) and 3,4-methylenedioxymethamphetamine (MDMA) on diverse neuroinflammation and neurotoxic markers. Male and female Wistar rats were chronically treated with increasing doses of THC and/or MDMA during adolescence. The effects of THC and/or MDMA on glial reactivity and on serotoninergic and cannabinoid systems were assessed by immunohistochemistry in the hippocampus and parietal cortex. THC increased the area staining for glial fibrilar acidic protein in both sexes. In males, both drugs, either separately or in combination, increased the proportion of reactive microglia cells [ionized calcium binding adaptor molecule 1 (Iba-1)]. In contrast, in females, each drug, administered alone, decreased of this proportion, whereas the combination of both drugs resulted in a 'normalization' to control values. In males, MDMA reduced the number of SERT positive fibres, THC induced the opposite effect and the group receiving both drugs did not significantly differ from the controls. In females, MDMA reduced the number of SERT positive fibres and the combination of both drugs counteracted this effect. THC also reduced immunostaining for CB1 receptors in females and this effect was aggravated by the combination with MDMA. Adolescent exposure of rats to THC and/or MDMA induced long-term, sex-dependent neurochemical and glial alterations, and revealed interactions between the two drugs. This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6. © 2013 The British Pharmacological Society.

Long-term effects of x-ray irradiation on reproductive function in male rats

International Nuclear Information System (INIS)

Varga, S.V.; Demchenko, V.N.; Chajkovskaya, L.V.; Reznikov, A.G.

1994-01-01

Reproductive function in male rats was studied in 1, 3 and 6 months after x-ray irradiation at doses of 2 and 3 Gy. It was been established that long-term effects of irradiation at a dose of 3 Gy are manifested through decrease in spermatozoa content in the epididymis and reduction of nucleie acid and protein content in the testes. Fertility of male rats under study significantly lowered shortly after irradiation and full recovery of fecundating ability was observed 6 months later. The effect of irradiation with a dose of 2 Gy was less pronounced

Long-term Dose Stability of OnabotulinumtoxinA Injection for Adductor Spasmodic Dysphonia: A 19-Year Single Institution Experience

Directory of Open Access Journals (Sweden)

Paul Paddle

2017-11-01

Full Text Available ObjectivesAdductor spasmodic dysphonia (AdSD is a focal dystonia predominantly involving the laryngeal adductor muscles. AdSD is reported to be a largely non-progressive neurological disorder, though fluctuations in symptom severity do occur. Repeated laryngeal onabotulinumtoxinA (BTX-A injections are the primary management for AdSD. A number of studies have demonstrated long-term dose stability as evidence of this long-term disease stability.MethodsA retrospective review was performed on all patients undergoing BTX-A injections for AdSD from April 1994 to September 2013 by a single laryngologist at a tertiary referral laryngology center. Patient demographics, injection doses, use of diazepam and/or lidocaine, and self-reported vocal function were recorded. Multiple linear regression analyses were performed.Results83 patients underwent a total of 1,168 injections over 19 years. The mean starting dose was 2.35 MU (0.79 SD. The mean long-term dose was 2.36 MU (0.79 SD. After adjusting for confounders, the change in the relative dose of BTX-A, with every year elapsed since initial dose was 0.13% (95% confidence interval −0.31 to 0.57%, p = 0.568.ConclusionBTX-A dose is stable over time in our large cohort of patients treated with bilateral thyroarytenoid injections for AdSD.

[Long-term effectiveness of psychodynamic outpatient treatment of addiction].

Science.gov (United States)

Steffen, D V; Werle, L; Steffen, R; Steffen, M; Steffen, S

2012-07-01

The aim of this study is to make an evaluation of the effectiveness of long-term outpatient treatment for addiction on the basis of abstinence, cognitive functions, and changes in personality structure. This is a prospective cohort study of 259 patients with registration of the German core data set "addiction", a 12-month follow-up and neuropsychological testing (personality inventory, intelligence and cognitive functions). One year after the end of the long-term treatment we see an abstinence rate (DGSS4) of 57.5 %. The most substantial factors in abstinence are the participation in a self-help-group (β = 0.734, p addiction seem to show its high effectiveness in terms of abstinence and processing of drug structures. The cognitive functions could increase. This could be determinate of a condition for the conservation and restoration of working capacity. Further studies should differentiate the effect of insight into the dependency structure from the abstinence as an specific or unspecific effect. © Georg Thieme Verlag KG Stuttgart · New York.

Long-term dose-response studies of inhaled or injected radionuclides

International Nuclear Information System (INIS)

Boecker, B.B.; Muggenburg, B.A.; Miller, S.C.; Bradley, P.L.

1994-01-01

This report describes the scientific progress in, and current status of, life-span studies of the long-term health risks in Beagle dogs of chronic irradiation from internally deposited radionuclides or from an external source. The reporting period for this document is the 2-year period from October 1, 1991 through September 30, 1993. Studies that were initiated at three different laboratories (Inhalation Toxicology Research Institute, ITRI, University of Utah, and Argonne National Laboratory, ANL) are presented here because they are being completed at ITRI. All living dogs in the Utah-initiated studies were transferred to the ITRI facility for the remainder of their life-span observations and measurements in September 1987. This report is the fourth in a series of reports dealing with the current status and progress of both the Utah and ITRI studies. Other life-span studies involving dogs exposed to gamma radiation from an external source were initiated and conducted for many years at ANL. In 1991, the decision was made to discontinue the chronic irradiation of the remaining living dogs and to transfer all remaining dogs to ITRI for care, clinical observations, and pathological observations at death or euthanasia. This report provides the current status of these dogs. Status reports on the Utah and ITRI studies comprise most of this report. The ITRI-related section presents brief statements of project objectives, the general procedures used in these studies, and some study-specific features for each of the 19 studies being conducted with either beta- or alpha-emitting radionuclides. Dose- and effect-modifying factors being addressed in these studies include total dose, dose rate, LET, solubility, nonuniformity of dose, species, age, sex, health status, and mode of exposure. Recent additions to experimental protocols for studies in which dogs are still alive involve the collection and analysis of tumor tissues using currently available molecular biology techniques

Long term effects of low doses of ionising radiation: facts and fallacies

International Nuclear Information System (INIS)

Iyer, G.K.

1993-01-01

Health effects of low doses of ionising radiation have been a public concern. The public perception of these low effects is that it causes cancer and genetic effects. Enormous amount of work regarding this cancer has been done all over the world, on occupational workers exposed to low doses of ionising radiation. These studies do not show any adverse effect on them. Epidemiological studies done on members of public staying near nuclear facilities also have shown that there is no health risk involved in staying near these facilities. Genetic effects have also shown negative results. These two aspects of health effects of low dose of radiation are discussed in detail. (author). 5 refs., 1 tab

Alpha2-adrenoceptor modulation of long-term potentiation elicited in vivo in rat occipital cortex.

Science.gov (United States)

Mondaca, Mauricio; Hernández, Alejandro; Pérez, Hernán; Valladares, Luis; Sierralta, Walter; Fernández, Victor; Soto-Moyano, Rubén

2004-09-24

Pretreatment with the alpha(2)-adrenoceptor agonist clonidine (31.25, 62.5, or 125 microg/kg, i.p.) dose-dependently reduced long-term potentiation (LTP) elicited in vivo in the occipital cortex of anesthetized rats, whereas pretreatment with the alpha(2)-adrenoceptor antagonist yohimbine (0.133, 0.4, or 1.2 mg/kg, i.p.) increased neocortical LTP in a dose-dependent fashion. These effects could be related to the reported disruptive and facilitatory actions induced on memory formation by pretreatment with alpha(2)-adrenoceptor agonists and antagonists, respectively.

Long-term outcomes and cost effectiveness of high-dose dexamethasone for cardiac surgery : A randomised trial

NARCIS (Netherlands)

Dieleman, J. M.; de Wit, G. A.; Nierich, A. P.; Rosseel, P. M.; van der Maaten, J. M.; Hofland, J.; Diephuis, J. C.; de Lange, F.; Boer, C.; Neslo, R. E.; Moons, K. G.; van Herwerden, L. A.; Tijssen, J. G.; Kalkman, C. J.; van Dijk, D.

Prophylactic intra-operative administration of dexamethasone may improve short-term clinical outcomes in cardiac surgical patients. The purpose of this study was to evaluate long-term clinical outcomes and cost effectiveness of dexamethasone versus placebo. Patients included in the multicentre,

Long-term outcomes and cost effectiveness of high-dose dexamethasone for cardiac surgery: a randomised trial

NARCIS (Netherlands)

Dieleman, J. M.; de Wit, G. A.; Nierich, A. P.; Rosseel, P. M.; van der Maaten, J. M.; Hofland, J.; Diephuis, J. C.; de Lange, F.; Boer, C.; Neslo, R. E.; Moons, K. G.; van Herwerden, L. A.; Tijssen, J. G.; Kalkman, C. J.; van Dijk, D.

2017-01-01

Prophylactic intra-operative administration of dexamethasone may improve short-term clinical outcomes in cardiac surgical patients. The purpose of this study was to evaluate long-term clinical outcomes and cost effectiveness of dexamethasone versus placebo. Patients included in the multicentre,

A long-term risk-benefit analysis of low-dose aspirin in primary prevention.

Science.gov (United States)

Wu, I-Chen; Hsieh, Hui-Min; Yu, Fang-Jung; Wu, Meng-Chieh; Wu, Tzung-Shiun; Wu, Ming-Tsang

2016-02-01

The long-term risk-benefit effect of occasional and regular use of low-dose aspirin (≤ 100 mg per day) in primary prevention of vascular diseases and cancers was calculated. One representative database of 1 000 000 participants from Taiwan's National Health Insurance scheme in 1997-2000 was used. The potential study subjects were those aged 30-95 years, were found not to have been prescribed aspirin before 1 January 2000, but to have first been prescribed low-dose aspirin (≤ 100 mg per day) after that date and were followed up to 31 December 2009. Participants prescribed low-dose aspirin risk. A total of 1720 pairs were analysed. During the study period, haemorrhage and ischaemia occurred in 25 (1·45%) and 67 participants (3·90%) in occasional users and 69 (4·01%) and 100 participants (5·81%) in regular users, whereas cancer occurred in 32 participants (1·86%) in occasional users and 26 participants (1·51%) in regular users. The crude and adjusted net clinical risks of low-dose aspirin use between the two frequency of users (≥ 80% vs. prevention against major vascular diseases and cancer. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Long-term social recognition memory is mediated by oxytocin-dependent synaptic plasticity in the medial amygdala.

Science.gov (United States)

Gur, Rotem; Tendler, Alex; Wagner, Shlomo

2014-09-01

Recognition of specific individuals is fundamental to mammalian social behavior and is mediated in most mammals by the main and accessory olfactory systems. Both these systems innervate the medial amygdala (MeA), where activity of the neuropeptide oxytocin is thought to mediate social recognition memory (SRM). The specific contribution of the MeA to SRM formation and the specific actions of oxytocin in the MeA are unknown. We used the social discrimination test to evaluate short-term and long-term SRM in adult Sprague-Dawley male rats (n = 38). The role of protein synthesis in the MeA was investigated by local application of the protein synthesis blocker anisomycin (n = 11). Synaptic plasticity was assessed in vivo by recording the MeA evoked field potential responses to stimulation of the main (n = 21) and accessory (n = 56) olfactory bulbs before and after theta burst stimulation. Intracerebroventricular administration of saline, oxytocin, or oxytocin receptor antagonist was used to measure the effect of oxytocin on synaptic plasticity. Anisomycin application to the MeA prevented the formation of long-term SRM. In addition, the responses of MeA neurons underwent long-term depression (LTD) after theta burst stimulation of the accessory olfactory bulb, but not the main accessory bulb, in an oxytocin-dependent manner. No LTD was found in socially isolated rats, which are known to lack long-term SRM. Finally, accessory olfactory bulb stimulation before SRM acquisition blocked long-term SRM, supporting the involvement of LTD in the MeA in formation of long-term SRM. Our results indicate that long-term SRM in rats involves protein synthesis and oxytocin-dependent LTD in the MeA. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Are long-term bisphosphonate users a reality?

DEFF Research Database (Denmark)

Abrahamsen, B

2012-01-01

The prevalence of long-term bisphosphonate use may be low due to low refill compliance and gaps in treatment. An analysis of the prescription history of 58,674 bisphosphonate users in Denmark found that only 2.8 % had received ten dose years of treatment or above. INTRODUCTION: This study aims...... to describe the demographics of present bisphosphonate (BP) users, to determine the prevalence of long-term BP use, and to establish if long-term use (a 10-year history of osteoporosis treatment) translated to ten dose years of bisphosphonate prescriptions filled, given the propensity for treatment gaps...... more than ten dose years of a BP. For any osteoporosis drug, 3.0 % had received ten dose years or more, while 23.2 % had received between 5 and 10 years of treatment. CONCLUSION: Long-term users with ten dose years or more of a BP are rare due to periods of low compliance and gaps, with a discrepancy...

The Effect of Dose Rate on Composite Durability When Exposed to a Simulated Long-Term Lunar Radiation Environment

Science.gov (United States)

Rojdev, Kristina; O'Rourke, Mary Jane; Hill, Charles; Nutt, Steven; Atwell, William

2011-01-01

Human exploration of space beyond low Earth orbit (LEO) requires a safe living and working environment for crew. Composite materials are one type of material being investigated by NASA as a multi-functional structural approach to habitats for long-term use in space or on planetary surfaces with limited magnetic fields and atmosphere. These materials provide high strength with the potential for decreased weight and increased radiation protection of crew and electronics when compared with conventional aluminum structures. However, these materials have not been evaluated in a harsh radiation environment, as would be experienced outside of LEO or on a planetary surface. Thus, NASA has been investigating the durability of select composite materials in a long-term radiation environment. Previously, NASA exposed composite samples to a simulated, accelerated 30-year radiation treatment and tensile stresses similar to those of a habitat pressure vessel. The results showed evidence of potential surface oxidation and enhanced cross-linking of the matrix. As a follow-on study, we performed the same accelerated exposure alongside an exposure with a decreased dose rate. The slower dose ]rate is comparable to a realistic scenario, although still accelerated. Strain measurements were collected during exposure and showed that with a fastdose rate, the strain decreased with time, but with a slow ]dose rate, the strain increased with time. After the radiation exposures, samples were characterized via tensile tests, flexure tests, Fourier Transform Infrared Spectroscopy (FTIR), and Differential Scanning Calorimetry (DSC). The results of these tests will be discussed.

Long-term effects of childbirth in MS

NARCIS (Netherlands)

D'hooghe, M.B.; Nagels, G.; Uitdehaag, B.M.J.

2010-01-01

Background: The uncertainty about long-term effects of childbirth presents MS patients with dilemmas. Methods: Based on clinical data of 330 female MS patients, the long-term effects of childbirth were analysed, using a cross-sectional study design. Four groups of patients were distinguished: (1)

Differential Long-Term Effects of Haloperidol and Risperidone on the Acquisition and Performance of Tasks of Spatial Working and Short-Term Memory and Sustained Attention in Rats

Science.gov (United States)

Hutchings, Elizabeth J.; Waller, Jennifer L.

2013-01-01

A common feature of the neuropsychiatric disorders for which antipsychotic drugs are prescribed is cognitive dysfunction, yet the effects of long-term antipsychotic treatment on cognition are largely unknown. In the current study, we evaluated the effects of long-term oral treatment with the first-generation antipsychotic haloperidol (1.0 and 2.0 mg/kg daily) and the second-generation antipsychotic risperidone (1.25 and 2.5 mg/kg daily) on the acquisition and performance of two radial-arm maze (RAM) tasks and a five-choice serial reaction-time task (5C-SRTT) in rats during days 15–60 and 84–320 days of treatment, respectively. In the RAM, neither antipsychotic significantly affected the acquisition or performance of a spatial win shift or a delayed non–match-to-position task. Conversely, in the rats administered 5C-SRTT, haloperidol was associated with profound deficits in performance, and the subjects were not able to progress through all stages of task acquisition. Depending on the dose, risperidone was associated with a greater number of trials to meet specific performance criteria during task acquisition compared with vehicle-treated controls; however, most subjects were eventually able to achieve all levels of task acquisition. Both haloperidol and risperidone also increased the number of perseverative and time-out responses during certain stages of task acquisition, and the response and reward latencies were slightly higher than controls during several stages of the study. These results in rats suggest that while long-term treatment with haloperidol or risperidone may not significantly affect spatial working or short-term memory, both antipsychotics can (depending on dose) impair sustained attention, decrease psychomotor speed, increase compulsive-type behaviors, and impair cognitive flexibility. PMID:24042161

Differential long-term effects of haloperidol and risperidone on the acquisition and performance of tasks of spatial working and short-term memory and sustained attention in rats.

Science.gov (United States)

Hutchings, Elizabeth J; Waller, Jennifer L; Terry, Alvin V

2013-12-01

A common feature of the neuropsychiatric disorders for which antipsychotic drugs are prescribed is cognitive dysfunction, yet the effects of long-term antipsychotic treatment on cognition are largely unknown. In the current study, we evaluated the effects of long-term oral treatment with the first-generation antipsychotic haloperidol (1.0 and 2.0 mg/kg daily) and the second-generation antipsychotic risperidone (1.25 and 2.5 mg/kg daily) on the acquisition and performance of two radial-arm maze (RAM) tasks and a five-choice serial reaction-time task (5C-SRTT) in rats during days 15-60 and 84-320 days of treatment, respectively. In the RAM, neither antipsychotic significantly affected the acquisition or performance of a spatial win shift or a delayed non-match-to-position task. Conversely, in the rats administered 5C-SRTT, haloperidol was associated with profound deficits in performance, and the subjects were not able to progress through all stages of task acquisition. Depending on the dose, risperidone was associated with a greater number of trials to meet specific performance criteria during task acquisition compared with vehicle-treated controls; however, most subjects were eventually able to achieve all levels of task acquisition. Both haloperidol and risperidone also increased the number of perseverative and time-out responses during certain stages of task acquisition, and the response and reward latencies were slightly higher than controls during several stages of the study. These results in rats suggest that while long-term treatment with haloperidol or risperidone may not significantly affect spatial working or short-term memory, both antipsychotics can (depending on dose) impair sustained attention, decrease psychomotor speed, increase compulsive-type behaviors, and impair cognitive flexibility.

Effects of Long Term Supplementation of Anabolic Androgen Steroids on Human Skeletal Muscle

Science.gov (United States)

Yu, Ji-Guo; Bonnerud, Patrik; Eriksson, Anders; Stål, Per S.; Tegner, Yelverton; Malm, Christer

2014-01-01

The effects of long-term (over several years) anabolic androgen steroids (AAS) administration on human skeletal muscle are still unclear. In this study, seventeen strength training athletes were recruited and individually interviewed regarding self-administration of banned substances. Ten subjects admitted having taken AAS or AAS derivatives for the past 5 to 15 years (Doped) and the dosage and type of banned substances were recorded. The remaining seven subjects testified to having never used any banned substances (Clean). For all subjects, maximal muscle strength and body composition were tested, and biopsies from the vastus lateralis muscle were obtained. Using histochemistry and immunohistochemistry (IHC), muscle biopsies were evaluated for morphology including fiber type composition, fiber size, capillary variables and myonuclei. Compared with the Clean athletes, the Doped athletes had significantly higher lean leg mass, capillary per fibre and myonuclei per fiber. In contrast, the Doped athletes had significantly lower absolute value in maximal squat force and relative values in maximal squat force (relative to lean body mass, to lean leg mass and to muscle fiber area). Using multivariate statistics, an orthogonal projection of latent structure discriminant analysis (OPLS-DA) model was established, in which the maximal squat force relative to muscle mass and the maximal squat force relative to fiber area, together with capillary density and nuclei density were the most important variables for separating Doped from the Clean athletes (regression  =  0.93 and prediction  =  0.92, p<0.0001). In Doped athletes, AAS dose-dependent increases were observed in lean body mass, muscle fiber area, capillary density and myonuclei density. In conclusion, long term AAS supplementation led to increases in lean leg mass, muscle fiber size and a parallel improvement in muscle strength, and all were dose-dependent. Administration of AAS may induce sustained

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)

Biochemical effects on long-term frozen human costal cartilage

International Nuclear Information System (INIS)

Santin, Stefany P.; Martinho Junior, Antonio C.; Yoshito, Daniele; Soares, Fernando A.N.; Mathor, Monica B.

2011-01-01

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)

[Dose rate-dependent cellular and molecular effects of ionizing radiation].

Science.gov (United States)

Przybyszewski, Waldemar M; Wideł, Maria; Szurko, Agnieszka; Maniakowski, Zbigniew

2008-09-11

The aim of radiation therapy is to kill tumor cells while minimizing damage to normal cells. The ultimate effect of radiation can be apoptotic or necrotic cell death as well as cytogenetic damage resulting in genetic instability and/or cell death. The destructive effects of radiation arise from direct and indirect ionization events leading to peroxidation of macromolecules, especially those present in lipid-rich membrane structures as well as chromatin lipids. Lipid peroxidative end-products may damage DNA and proteins. A characteristic feature of radiation-induced peroxidation is an inverse dose-rate effect (IDRE), defined as an increase in the degree of oxidation(at constant absorbed dose) accompanying a lower dose rate. On the other hand, a low dose rate can lead to the accumulation of cells in G2, the radiosensitive phase of the cell cycle since cell cycle control points are not sensitive to low dose rates. Radiation dose rate may potentially be the main factor improving radiotherapy efficacy as well as affecting the intensity of normal tissue and whole-body side effects. A better understanding of dose rate-dependent biological effects may lead to improved therapeutic intervention and limit normal tissue reaction. The study reviews basic biological effects that depend on the dose rate of ionizing radiation.

Long-term effects of 239Pu injection in adult, weanling, newborn and fetal rats

International Nuclear Information System (INIS)

Sikov, M.R.; Mahlum, D.D.; Hess, J.O.; Carr, D.B.

1979-01-01

We have completed biological evaluations comparing long-term effects in rats exposed to 239 Pu citrate as adults, weanlings, newborns, or late fetuses, and statistical analyses have been initiated. In rats exposed postnatally, statistically significant alterations in terminal body weight and in weights of several organs were found at higher doses. Survivorship decreased with increasing dose in the postnatal groups, but not in rats exposed prenatally

Short and long-term effects of azadirachtin A on development and egg production of Rhodnius prolixus

Directory of Open Access Journals (Sweden)

Eloi S. Garcia

1990-03-01

Full Text Available Azadirachtin A was given through a blood meal to 4th-instar larvae and to adult females of Rhodnius prolixus. Development (ecdysis and egg production were inhibited in a dose-dependent manner. Long-term experiments with subsequent four feedings on azadirachtin-free blood were performed with 4th-instar larvae and with adult females. Only in the low-dose azadirachtin larval groups (0.01 and 0.1 microng/ml of blood, development was partially restored; after a single 1.0 microng/ml treatment about 50% of the treated larvae were still alive 120 days later without any adult emergence. Similarly fed females had a dose-dependent lower survival and egg deposition rate. The results are discussed in relation to the mode of azadirachtin A action.

rhEPO Enhances Cellular Anti-oxidant Capacity to Protect Long-Term Cultured Aging Primary Nerve Cells.

Science.gov (United States)

Wang, Huqing; Fan, Jiaxin; Chen, Mengyi; Yao, Qingling; Gao, Zhen; Zhang, Guilian; Wu, Haiqin; Yu, Xiaorui

2017-08-01

Erythropoietin (EPO) may protect the nervous system of animals against aging damage, making it a potential anti-aging drug for the nervous system. However, experimental evidence from natural aging nerve cell models is lacking, and the efficacy of EPO and underlying mechanism of this effect warrant further study. Thus, the present study used long-term cultured primary nerve cells to successfully mimic the natural aging process of nerve cells. Starting on the 11th day of culture, cells were treated with different concentrations of recombinant human erythropoietin (rhEPO). Using double immunofluorescence labeling, we found that rhEPO significantly improved the morphology of long-term cultured primary nerve cells and increased the total number of long-term cultured primary cells. However, rhEPO did not improve the ratio of nerve cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure nerve cell activity and showed that rhEPO significantly improved the activity of long-term cultured primary nerve cells. Moreover, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double immunofluorescence labeling flow cytometry revealed that rhEPO reduced the apoptotic rate of long-term cultured primary nerve cells. Senescence-associated β-galactosidase (SA-β-gal) immunohistochemistry staining showed that rhEPO significantly reduced the aging rate of long-term cultured primary nerve cells. Immunochemistry revealed that rhEPO enhanced intracellular superoxide dismutase (SOD) activity and glutathione (GSH) abundance and reduced the intracellular malondialdehyde (MDA) level. In addition, this effect depended on the dose, was maximized at a dose of 100 U/ml and was more pronounced than that of vitamin E. In summary, this study finds that rhEPO protects long-term cultured primary nerve cells from aging in a dose-dependent manner. The mechanism of this effect may be associated with the enhancement of the intracellular anti

A trial epidemiological study on health effects of long term and low level radiation exposure

International Nuclear Information System (INIS)

Hattori, Yoshiaki; Maeda, Kazuho

1980-01-01

As a trial evaluation of applicability of multivariate model in an analysis of health effects of radiation workers, the multiple logistic function method was applied to the data of occupational exposure record and long term absence record obtained from 593 employees of two institutions both of which practice R and D relating nuclear power. In order to estimate parameters of multiple logistic function by maximum likelihood method, followings were defined as variables: age, length of employment and cumulative exposure dose of radiation as independent variables, and the fact that whether the individual worker had the experience of absence lasting more than a week or not as a dependent variable. As the results, due to shortage of amount of data, only the age of workers shows a significant relationship with the absence data, the other variables do not have any significant results in the association with absence. In this preliminary trial, the applicability of multiple logistic function model in risk estimation of long term occupational exposure was not clearly demonstrated because of data shortage. To testify the applicability, further investigations will be needed, accumulating plenty of data concerning exposure and health effects. (author)

Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies

Science.gov (United States)

García Rodríguez, Luis A.; Martín-Pérez, Mar; Hennekens, Charles H.; Rothwell, Peter M.; Lanas, Angel

2016-01-01

Background Low-dose aspirin has proven effectiveness in secondary and primary prevention of cardiovascular events, but is also associated with an increased risk of major bleeding events. For primary prevention, this absolute risk must be carefully weighed against the benefits of aspirin; such assessments are currently limited by a lack of data from general populations. Methods Systematic searches of Medline and Embase were conducted to identify observational studies published between 1946 and 4 March 2015 that reported the risks of gastrointestinal (GI) bleeding or intracranial hemorrhage (ICH) with long-term, low-dose aspirin (75–325 mg/day). Pooled estimates of the relative risk (RR) for bleeding events with aspirin versus non-use were calculated using random-effects models, based on reported estimates of RR (including odds ratios, hazard ratios, incidence rate ratios and standardized incidence ratios) in 39 articles. Findings The incidence of GI bleeding with low-dose aspirin was 0.48–3.64 cases per 1000 person-years, and the overall pooled estimate of the RR with low-dose aspirin was 1.4 (95% confidence interval [CI]: 1.2–1.7). For upper and lower GI bleeding, the RRs with low-dose aspirin were 2.3 (2.0–2.6) and 1.8 (1.1–3.0), respectively. Neither aspirin dose nor duration of use had consistent effects on RRs for upper GI bleeding. The estimated RR for ICH with low-dose aspirin was 1.4 (1.2–1.7) overall. Aspirin was associated with increased bleeding risks when combined with non-steroidal anti-inflammatory drugs, clopidogrel and selective serotonin reuptake inhibitors compared with monotherapy. By contrast, concomitant use of proton pump inhibitors decreased upper GI bleeding risks relative to aspirin monotherapy. Conclusions The risks of major bleeding with low-dose aspirin in real-world settings are of a similar magnitude to those reported in randomized trials. These data will help inform clinical judgements regarding the use of low-dose aspirin

Density-dependent microbial turnover improves soil carbon model predictions of long-term litter manipulations

Science.gov (United States)

Georgiou, Katerina; Abramoff, Rose; Harte, John; Riley, William; Torn, Margaret

2017-04-01

Climatic, atmospheric, and land-use changes all have the potential to alter soil microbial activity via abiotic effects on soil or mediated by changes in plant inputs. Recently, many promising microbial models of soil organic carbon (SOC) decomposition have been proposed to advance understanding and prediction of climate and carbon (C) feedbacks. Most of these models, however, exhibit unrealistic oscillatory behavior and SOC insensitivity to long-term changes in C inputs. Here we diagnose the sources of instability in four models that span the range of complexity of these recent microbial models, by sequentially adding complexity to a simple model to include microbial physiology, a mineral sorption isotherm, and enzyme dynamics. We propose a formulation that introduces density-dependence of microbial turnover, which acts to limit population sizes and reduce oscillations. We compare these models to results from 24 long-term C-input field manipulations, including the Detritus Input and Removal Treatment (DIRT) experiments, to show that there are clear metrics that can be used to distinguish and validate the inherent dynamics of each model structure. We find that widely used first-order models and microbial models without density-dependence cannot readily capture the range of long-term responses observed across the DIRT experiments as a direct consequence of their model structures. The proposed formulation improves predictions of long-term C-input changes, and implies greater SOC storage associated with CO2-fertilization-driven increases in C inputs over the coming century compared to common microbial models. Finally, we discuss our findings in the context of improving microbial model behavior for inclusion in Earth System Models.

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

Directory of Open Access Journals (Sweden)

Scott J. Sherman

2016-02-01

Full Text Available 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.

Radiotherapy for benign achillodynia. Long-term results of the Erlangen Dose Optimization Trial

Energy Technology Data Exchange (ETDEWEB)

Ott, Oliver J.; Jeremias, Carolin; Gaipl, Udo S.; Frey, Benjamin; Schmidt, Manfred; Fietkau, Rainer [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany)

2015-12-15

The aim of this study was to evaluate the long-term efficacy of two dose-fractionation schedules for radiotherapy of achillodynia. Between February 2006 and February 2010, 112 evaluable patients were recruited for this prospective trial. All patients received orthovoltage radiotherapy. One course consisted of 6 fractions/3 weeks. In the case of insufficient remission of pain after 6 weeks, a second series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. The endpoint was pain reduction. Pain was measured before, right after (early response), 6 weeks after (delayed response), and approximately 2 years after radiotherapy (long-term response) with a questionnaire-based visual analogue scale (VAS) and a comprehensive pain score (CPS). The median follow-up was 24 months (range, 11-56). The overall early, delayed, and long-term response rates for all patients were 84 %, 88 %, and 95 %, respectively. The mean VAS values before treatment for early, delayed, and long-term responses for the 0.5-Gy and 1.0-Gy groups were 55.7 ± 21.0 and 58.2 ± 23.5 (p = 0.53), 38.0 ± 23.2 and 30.4 ± 22.6 (p = 0.08), 35.5 ± 25.9 and 30.9 ± 25.4 (p = 0.52), and 11.2 ± 16.4 and 15.3 ± 18.9 (p = 0.16), respectively. The mean CPS values before treatment for early, delayed, and long-term responses were 8.2 ± 3.0 and 8.9 ± 3.3 (p = 0.24), 5.6 ± 3.1 and 5.4 ± 3.3 (p = 0.76), 4.4 ± 2.6 and 5.3 ± 3.8 (p = 0.58), and 2.2 ± 2.9 and 2.8 ± 3.3 (p = 0.51), respectively. No significant differences in long-term response quality between the two arms was found (p = 0.73). Radiotherapy is a very effective treatment for the management of benign achillodynia. For radiation protection, the dose for a radiotherapy series should not exceed 3.0 Gy. (orig.) [German] Ziel war die Untersuchung der Langzeiteffektivitaet zweier Dosisfraktionierungskonzepte bei der Strahlentherapie von Patienten mit Achillodynie. Zwischen 2006 und 2010 wurden 112 auswertbare

Long-term effects of an intracavitary treatment with californium-252 on normal tissue

International Nuclear Information System (INIS)

Sullivan, M.F.; Beamer, J.L.; Mahony, T.D.; Cross, F.T.; Lund, J.E.; Endres, G.W.R.

1976-01-01

About one hundred fifty swine were exposed to either radium-226 or californium-252 sources in the uterine cervix to determine an RBE for both acute and long-term effects. That value for early changes in the tissues at risk in the treatment of cervical cancer was between 6.2 and 6.8. The incidence of complications increased with time after exposure, especially among animals treated with 252 Cf. Analysis of rectal injury showed that ulceration occurred frequently within a year postexposure at doses between 1600 and 2400 rad calculated at 2 cm lateral to the source midline. Fat necrosis and smooth muscle atrophy, resulting in a local rectal stricture, were delayed changes observed in some animals. The lower ureter was the site for a greater frequency of complications than the GI tract. Ureteral stricture often occurred at doses of 1200 rad from 252 Cf and 7000 rad from 226 Ra. Observation of delayed effects in the uterine-cervix in animals held up to 4 years postexposure indicate that the RBE for 252 Cf may be increased to a value as high as 18, while repair may have even decreased it to about 5.6 in the rectum. Fifty swine are still being observed for long-term effects after doses above 800 rad from 252 Cf and 5000 rad from 226 Ra

Significant long-term, but not short-term, hippocampal-dependent memory impairment in adult rats exposed to alcohol in early postnatal life.

Science.gov (United States)

Goodfellow, Molly J; Lindquist, Derick H

2014-09-01

In rodents, ethanol exposure in early postnatal life is known to induce structural and functional impairments throughout the brain, including the hippocampus. Herein, rat pups were administered one of three ethanol doses over postnatal days (PD) 4-9, a period of brain development comparable to the third trimester of human pregnancy. As adults, control and ethanol rats were trained and tested in a variant of hippocampal-dependent one-trial context fear conditioning. In Experiment 1, subjects were placed into a novel context and presented with an immediate footshock (i.e., within ∼8 sec). When re-exposed to the same context 24 hr later low levels of conditioned freezing were observed. Context pre-exposure 24 hr prior to the immediate shock reversed the deficit in sham-intubated and unintubated control rats, enhancing freezing behavior during the context retention test. Even with context pre-exposure, however, significant dose-dependent reductions in contextual freezing were seen in ethanol rats. In Experiment 2, the interval between context pre-exposure and the immediate shock was shortened to 2 hr, in addition to the standard 24 hr. Ethanol rats trained with the 2 hr, but not 24 hr, interval displayed retention test freezing levels roughly equal to controls. Results suggest the ethanol rats can encode a short-term context memory and associate it with the aversive footshock 2 hr later. In the 24 hr ethanol rats the short-term context memory is poorly transferred or consolidated into long-term memory, we propose, impeding the memory's subsequent retrieval and association with shock. © 2014 Wiley Periodicals, Inc.

Biological effects of petroleum hydrocarbons: Predictions of long-term effects and recovery

International Nuclear Information System (INIS)

Capuzzo, J.M.

1990-01-01

Biological effects of petroleum hydrocarbons on marine organisms and ecosystems are dependent on the persistence and bioavailability of specific hydrocarbons, the ability of organisms to accumulate and metabolize various hydrocarbons, the fate of metabolized products, and the interference of specific hydrocarbons with normal metabolic processes that may alter an organism's chances for survival and reproduction in the environment. In considering the long-term effects of petroleum hydrocarbons on marine ecosystems it is important to ascertain what biological effects may result in subtle ecological changes, changes in community structure and function, and possible impairment of fisheries resources. It is also important to understand which hydrocarbons persist in benthic environments and the sublethal effects that lead to reduced growth, delayed development and reduced reproductive effort, population decline and the loss of that population's function in marine communities. Only through a multi-disciplinary approach to the study of the fate, transport and effects of petroleum hydrocarbons on marine ecosystems will there be a significant improvement in the ability to predict the long-term effects of oil spills and to elucidate the mechanisms of recovery

Dose and time dependent ototoxicity of aspartame in rats.

Science.gov (United States)

Ozturan, Orhan; Dogan, Remzi; Tugrul, Selahattin; Gedik, Ozge; Sjostrand, Alev Pektas; Yildirim, Yavuz Selim

2017-04-01

Low-dose administration of Aspartame (Ap) did not produce a significant ototoxic effect at the end of the 6th month. However, duration of the ototoxic effect is shortened and severity of the effect is increased as dose and duration of Ap administration is increased. While Ap toxicity has been studied in short- and long-term studies, its effects on hearing have not been investigated. This study was conducted to evaluate the effects of long-term consumption of Ap administered in various doses on hearing status of rats. The study included 54 female Wistar Albino rats. Ap was given for 6 months to the rats. The groups were assigned according to levels of Ap dosage. DPOAE and ABR tests were utilized for serial hearing evaluations. Serial hearing measurement times were designed as baseline, 1st week, 2nd week, 1st, 2nd, 3rd, and 6th months. While audiological parameters deteriorated with 100 mg/kg/day dose after the 3rd month, ABR thresholds were elevated and DPOAE values were significantly decreased in 500 mg/kg/day and 1000 mg/kg/day applications after the 2nd month. In 2000 mg/kg/day and 4000 mg/kg/day applications, deteriorations in audiological parameters were detected as early as the first and second months; respectively.

Long-term consumption of aspartame and brain antioxidant defense status.

Science.gov (United States)

Abhilash, M; Sauganth Paul, M V; Varghese, Mathews V; Nair, R Harikumaran

2013-04-01

The present study investigated the effect of long-term intake of aspartame, a widely used artificial sweetener, on antioxidant defense status in the rat brain. Male Wistar rats weighing 150-175 g were randomly divided into three groups as follows: The first group was given aspartame at a dose of 500 mg/kg body weight (b.w.); the second group was given aspartame at dose of 1,000 mg/kg b.w., respectively, in a total volume of 3 mL of water; and the control rats received 3 mL of distilled water. Oral intubations were done in the morning, daily for 180 days. The concentration of reduced glutathione (GSH) and the activity of glutathione reductase (GR) were significantly reduced in the brain of rats that had received the dose of 1,000 mg/kg b.w. of aspartame, whereas only a significant reduction in GSH concentration was observed in the 500-mg/kg b.w. aspartame-treated group. Histopathological examination revealed mild vascular congestion in the 1,000 mg/kg b.w. group of aspartame-treated rats. The results of this experiment indicate that long-term consumption of aspartame leads to an imbalance in the antioxidant/pro-oxidant status in the brain, mainly through the mechanism involving the glutathione-dependent system.

Dose-dependent effects of endotoxin on neurobehavioral functions in humans.

Directory of Open Access Journals (Sweden)

Jan-Sebastian Grigoleit

Full Text Available Clinical and experimental evidence document that inflammation and increased peripheral cytokine levels are associated with depression-like symptoms and neuropsychological disturbances in humans. However, it remains unclear whether and to what extent cognitive functions like memory and attention are affected by and related to the dose of the inflammatory stimulus. Thus, in a cross-over, double-blind, experimental approach, healthy male volunteers were administered with either placebo or bacterial lipopolysaccharide (LPS at doses of 0.4 (n = 18 or 0.8 ng/kg of body weight (n = 16. Pro- and anti-inflammatory cytokines, norephinephrine and cortisol concentrations were analyzed before and 1, 1.75, 3, 4, 6, and 24 h after injection. In addition, changes in mood and anxiety levels were determined together with working memory (n-back task and long term memory performance (recall of emotional and neutral pictures of the International Affective Picture System. Endotoxin administration caused a profound transient physiological response with dose-related elevations in body temperature and heart rate, increases in plasma interleukin (IL-6, IL-10, tumor necrosis factor (TNF-α and IL-1 receptor antagonist (IL-1ra, salivary and plasma cortisol, and plasma norepinephrine. These changes were accompanied by dose-related decreased mood and increased anxiety levels. LPS administration did not affect accuracy in working memory performance but improved reaction time in the high-dose LPS condition compared to the control conditon. In contrast, long-term memory performance was impaired selectively for emotional stimuli after administration of the lower but not of the higher dose of LPS. These data suggest the existence of at least two counter-acting mechanisms, one promoting and one inhibiting cognitive performance during acute systemic inflammation.

Sleep facilitates long-term face adaptation

OpenAIRE

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

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...

Natural course of care dependency in residents of long-term care facilities: prospective follow-up study.

Science.gov (United States)

Caljouw, Monique A A; Cools, Herman J M; Gussekloo, Jacobijn

2014-05-22

Insight in the natural course of care dependency of vulnerable older persons in long-term care facilities (LTCF) is essential to organize and optimize individual tailored care. We examined changes in care dependency in LTCF residents over two 6-month periods, explored the possible predictive factors of change and the effect of care dependency on mortality. A prospective follow-up study in 21 Dutch long-term care facilities. 890 LTCF residents, median age 84 (Interquartile range 79-88) years participated. At baseline, 6 and 12 months, care dependency was assessed by the nursing staff with the Care Dependency Scale (CDS), range 15-75 points. Since the median CDS score differed between men and women (47.5 vs. 43.0, P = 0.013), CDS groups (low, middle and high) were based on gender-specific 33% of CDS scores at baseline and 6 months. At baseline, the CDS groups differed in median length of stay on the ward, urine incontinence and dementia (all P dependency status, predicted an increase in care dependency over time. The majority of residents were stable in their care dependency status over two subsequent 6-month periods. Highly care dependent residents showed an increased mortality risk. Awareness of the natural course of care dependency is essential to residents and their formal and informal caregivers when considering therapeutic and end-of-life care options.

Long term effect of radioactive iodine treatment in nontoxic multinodular goitre

International Nuclear Information System (INIS)

Nygaard, B.; Hegedues, L.; Gervil, M.; Hjalgrim Jensen, H.; Soee-Jensen, P.; Moelholm hansen, J.E.

1994-01-01

The aim of this study was to investigate the long term effect of 131 I treatment on thyroid function and size in patients with non-toxic multinodular goitre. The subjects were 69 consecutive patients with multinodular non-toxic goitre selected for 131 I treatment and followed for a minimum of 12 months. Outcome measures were standard thyroid function variable and ultrasonically determined thyroid volume before and after treatment. Fifty-nine patients were treated with a single dose of 131 I, 12 with tow doses, and one with four doses. In 45 patients treated with one dose who remained euthyroid the median thyroid volume was reduced from 73 (interquartile range 50-106) ml to 29 (interquartile range 23-48) ml at 24 months. The median reuction was 40 (22-48) ml, half of which occurred within three months. Patients treated with two doses as well as those developing hypo- or hyper-thyroidism also had a significant reduction in thyroid volume. Eleven patients develeoped hypothyroidism (cumulative five year risk 22%). Side effects were few. In conclusion we find that 131 I treatment of multinodular non-toxic goitre is an attractive alternative to surgery. (au) (19 refs.)

Patient Outcomes in Dose Reduction or Discontinuation of Long-Term Opioid Therapy: A Systematic Review.

Science.gov (United States)

Frank, Joseph W; Lovejoy, Travis I; Becker, William C; Morasco, Benjamin J; Koenig, Christopher J; Hoffecker, Lilian; Dischinger, Hannah R; Dobscha, Steven K; Krebs, Erin E

2017-08-01

Expert guidelines recommend reducing or discontinuing long-term opioid therapy (LTOT) when risks outweigh benefits, but evidence on the effect of dose reduction on patient outcomes has not been systematically reviewed. To synthesize studies of the effectiveness of strategies to reduce or discontinue LTOT and patient outcomes after dose reduction among adults prescribed LTOT for chronic pain. MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Library from inception through April 2017; reference lists; and expert contacts. Original research published in English that addressed dose reduction or discontinuation of LTOT for chronic pain. Two independent reviewers extracted data and assessed study quality using the U.S. Preventive Services Task Force quality rating criteria. All authors assessed evidence quality using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Prespecified patient outcomes were pain severity, function, quality of life, opioid withdrawal symptoms, substance use, and adverse events. Sixty-seven studies (11 randomized trials and 56 observational studies) examining 8 intervention categories, including interdisciplinary pain programs, buprenorphine-assisted dose reduction, and behavioral interventions, were found. Study quality was good for 3 studies, fair for 13 studies, and poor for 51 studies. Many studies reported dose reduction, but rates of opioid discontinuation ranged widely across interventions and the overall quality of evidence was very low. Among 40 studies examining patient outcomes after dose reduction (very low overall quality of evidence), improvement was reported in pain severity (8 of 8 fair-quality studies), function (5 of 5 fair-quality studies), and quality of life (3 of 3 fair-quality studies). Heterogeneous interventions and outcome measures; poor-quality studies with uncontrolled designs. Very low quality evidence suggests that several types of interventions may be effective to reduce or

Effect of long-term selenium supplementation on mortality

DEFF Research Database (Denmark)

Rayman, Margaret P.; Winther, Kristian Hillert; Pastor-Barriuso, Roberto

2018-01-01

Background: Selenium, an essential trace element, is incorporated into selenoproteins with a wide range of health effects. Selenoproteins may reach repletion at a plasma selenium concentration of ∼ 125 μg/L, at which point the concentration of selenoprotein P reaches a plateau; whether sustained...... concentrations higher than this are beneficial, or indeed detrimental, is unknown. Objective: In a population of relatively low selenium status, we aimed to determine the effect on mortality of long-term selenium supplementation at different dose levels. Design: The Denmark PRECISE study was a single...... for extension of the study and mortality assessment. Participants were randomly assigned to treatment with 100, 200, or 300 μg selenium/d as selenium-enriched-yeast or placebo-yeast for 5 years from randomization in 1998-1999 and were followed up for mortality for a further 10 years (through March 31, 2015...

An improved non-Markovian degradation model with long-term dependency and item-to-item uncertainty

Science.gov (United States)

Xi, Xiaopeng; Chen, Maoyin; Zhang, Hanwen; Zhou, Donghua

2018-05-01

It is widely noted in the literature that the degradation should be simplified into a memoryless Markovian process for the purpose of predicting the remaining useful life (RUL). However, there actually exists the long-term dependency in the degradation processes of some industrial systems, including electromechanical equipments, oil tankers, and large blast furnaces. This implies the new degradation state depends not only on the current state, but also on the historical states. Such dynamic systems cannot be accurately described by traditional Markovian models. Here we present an improved non-Markovian degradation model with both the long-term dependency and the item-to-item uncertainty. As a typical non-stationary process with dependent increments, fractional Brownian motion (FBM) is utilized to simulate the fractal diffusion of practical degradations. The uncertainty among multiple items can be represented by a random variable of the drift. Based on this model, the unknown parameters are estimated through the maximum likelihood (ML) algorithm, while a closed-form solution to the RUL distribution is further derived using a weak convergence theorem. The practicability of the proposed model is fully verified by two real-world examples. The results demonstrate that the proposed method can effectively reduce the prediction error.

The role of GABA in NMDA-dependent long term depression (LTD) of rat medial vestibular nuclei.

Science.gov (United States)

Grassi, S; Della Torre, G; Capocchi, G; Zampolini, M; Pettorossi, V E

1995-11-20

The role of GABA in NMDA-dependent long term depression (LTD) in the medial vestibular nuclei (MVN) was studied on rat brainstem slices. High frequency stimulation (HFS) of the primary vestibular afferents induces a long lasting reduction of the polysynaptic (N2) component of the field potentials recorded in the dorsal portion of the MVN. The induction but not the maintenance of this depression was abolished by AP5, a specific blocking agent for glutamate NMDA receptors. The involvement of GABA in mediating the depression was checked by applying the GABAA and GABAB receptor antagonists, bicuculline and saclofen, before and after HFS. Under bicuculline and saclofen perfusion, HFS provoked a slight potentiation of the N2 wave, while the N2 depression clearly emerged after drug wash-out. This indicates that GABA is not involved in inducing the long term effect, but it is necessary for its expression. Similarly, the LTD reversed and a slight potentiation appeared when both drugs were administered after its induction. Most of these effects were due to the bicuculline, suggesting that GABAA receptors contribute to LTD more than GABAB do. According to our results, it is unlikely that the long lasting vestibular depression is the result of a homosynaptic LTD. On the contrary, our findings suggest that the depression is due to an enhancement of the GABA inhibitory effect, caused by an HFS dependent increase in gabaergic interneuron activity, which resets vestibular neuron excitability at a lower level.

Long-term use of metformin and colorectal cancer risk in type II diabetics

DEFF Research Database (Denmark)

Cardel, Majken; Jensen, S. M.; Pottegård, Anton

2014-01-01

of prescriptions for a cumulative dose of 2000 g within 5 years prior to the index date. To control for potential confounders, we used unconditional logistic regression. We generated adjusted odds ratios (OR) for the association between metformin and CRC and performed subanalyses for selected subgroups...... and for the dose-response relation. We identified 2088 cases and 9060 controls during the study period. The association between long-term metformin use and CRC gave an adjusted OR at 0.83 (95% CI 0.68-1.00). A protective effect on CRC with long-term use of metformin was only evident for women (OR 0.66 vs. 0.......99 for men). There was a significant dose-response association of metformin use > 250 defined daily dose (DDD) and for the duration of metformin use > 1 year. We found an indication of a protective effect of long-term metformin use against CRC in type II diabetics, although this effect was only seen in women....

The Effect of Zinc Supplementation of Lactating Rats on Short-Term and Long-Term Memory of Their Male Offspring

Directory of Open Access Journals (Sweden)

Mohammad Karami

2013-12-01

Full Text Available Background: In this study the effect of zinc chloride (ZnCl2 administration on the short-term and long-term memory of rats were assessed. Methods: We enrolled six groups of adult female and control group of eight Wistar rats in each group. One group was control group with free access to food and water, and five groups drunk zinc chloride in different doses (20, 30, 50, 70 and 100 mg/kg/day in drinking water for two weeks during lactation .One month after birth, a shuttle box used to short- term and long-term memory and the latency in entering the dark chamber as well. Results: This experiment showed that maternal 70 mg/kg dietary zinc during lactation influenced the working memory of rats’ offspring in all groups. Rats received 100 mg/kg/day zinc during lactation so they had significant impairment in working memory (short-term of their offspring (P<0.05. There was no significant difference in reference (long-term memory of all groups. Conclusion: Drug consumption below70 mg/kg/day zinc chloride during lactation had no effect. While enhanced 100 mg/ kg/ day zinc in lactating rats could cause short-term memory impairment.

Long-term memory, sleep, and the spacing effect.

Science.gov (United States)

Bell, Matthew C; Kawadri, Nader; Simone, Patricia M; Wiseheart, Melody

2014-01-01

Many studies have shown that memory is enhanced when study sessions are spaced apart rather than massed. This spacing effect has been shown to have a lasting benefit to long-term memory when the study phase session follows the encoding session by 24 hours. Using a spacing paradigm we examined the impact of sleep and spacing gaps on long-term declarative memory for Swahili-English word pairs by including four spacing delay gaps (massed, 12 hours same-day, 12 hours overnight, and 24 hours). Results showed that a 12-hour spacing gap that includes sleep promotes long-term memory retention similar to the 24-hour gap. The findings support the importance of sleep to the long-term benefit of the spacing effect.

Metabolic interactions between low doses of benzo[a]pyrene and tributyltin in arctic charr (salvelinus alpinus): a long-term in vivo study

International Nuclear Information System (INIS)

Padros, Jaime; Pelletier, Emilien; Ribeiro, Ciro Oliveira

2003-01-01

We have previously reported that short-term, single exposure to a high dose of tributyltin (TBT), a widely used antifouling biocide, inhibited both the in vivo metabolism and metabolic activation of the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) in fish; (BaP), in turn, stimulated TBT metabolism. Here, we provide further mechanistic evidence of mutual metabolic interactions between BaP and TBT in response to long-term, repeated exposures to low doses. Juvenile Arctic charr (Salvelinus alpinus) received 10 separate ip injections (a single injection every 6 days) of BaP (3 mg/kg), TBT (0.3 mg/kg), or both in combination; control fish received corn oil vehicle only. Two days after the 2nd (Day 8), 6 th (Day 32), and 10th dose (Day 56), blood, bile, and liver samples were collected and analyzed for a suite of biomarkers. HPLC/fluorescence analysis indicated that TBT cotreatment inhibited the formation of (+)-anti-BaP diol-epoxide adducts with plasma albumin (53%, Day 8), hepatic DNA (27%, Day 32), or both albumin and globin (50 and 58%, Day 56) compared to BaP alone. This antagonistic interaction was associated with a time-dependent modulation (inhibition at Day 8, enhancement at Day 32) of both cytochrome P450 (P450)1A-mediated ethoxyresorufin O-deethylase (EROD) activity and biliary BaP metabolite formation. TBT cotreatment also inhibited (39%) the BaP-mediated induction of hepatic glutathione S-transferase (GST) activity observed at Day 8. Treatment with TBT alone increased EROD activity (60%) at Day 32, but decreased both GST activity (70 and 37%) and glutathione content (24% and 16%) at Days 32 and 56, respectively. GC/MS analysis revealed that, at Day 56, BaP cotreatment increased (200%) the levels of biliary butyltin compounds, including mono- and dibutyltin metabolites. This potentiative interaction was associated with a protective effect of BaP cotreatment against the TBT-mediated decreases in GST activity and glutathione content. The

Long-term exercise in mice has sex-dependent benefits on body composition and metabolism during aging.

Science.gov (United States)

McMullan, Rachel C; Kelly, Scott A; Hua, Kunjie; Buckley, Brian K; Faber, James E; Pardo-Manuel de Villena, Fernando; Pomp, Daniel

2016-11-01

Aging is associated with declining exercise and unhealthy changes in body composition. Exercise ameliorates certain adverse age-related physiological changes and protects against many chronic diseases. Despite these benefits, willingness to exercise and physiological responses to exercise vary widely, and long-term exercise and its benefits are difficult and costly to measure in humans. Furthermore, physiological effects of aging in humans are confounded with changes in lifestyle and environment. We used C57BL/6J mice to examine long-term patterns of exercise during aging and its physiological effects in a well-controlled environment. One-year-old male (n = 30) and female (n = 30) mice were divided into equal size cohorts and aged for an additional year. One cohort was given access to voluntary running wheels while another was denied exercise other than home cage movement. Body mass, composition, and metabolic traits were measured before, throughout, and after 1 year of treatment. Long-term exercise significantly prevented gains in body mass and body fat, while preventing loss of lean mass. We observed sex-dependent differences in body mass and composition trajectories during aging. Wheel running (distance, speed, duration) was greater in females than males and declined with age. We conclude that long-term exercise may serve as a preventive measure against age-related weight gain and body composition changes, and that mouse inbred strains can be used to characterize effects of long-term exercise and factors (e.g. sex, age) modulating these effects. These findings will facilitate studies on relationships between exercise and health in aging populations, including genetic predisposition and genotype-by-environment interactions. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Long-term memory for instrumental responses does not undergo protein synthesis-dependent reconsolidation upon retrieval.

Science.gov (United States)

Hernandez, Pepe J; Kelley, Ann E

2004-01-01

Recent evidence indicates that certain forms of memory, upon recall, may return to a labile state requiring the synthesis of new proteins in order to preserve or reconsolidate the original memory trace. While the initial consolidation of "instrumental memories" has been shown to require de novo protein synthesis in the nucleus accumbens, it is not known whether memories of this type undergo protein synthesis-dependent reconsolidation. Here we show that low doses of the protein synthesis inhibitor anisomycin (ANI; 5 or 20 mg/kg) administered systemically in rats immediately after recall of a lever-pressing task potently impaired performance on the following daily test sessions. We determined that the nature of this impairment was attributable to conditioned taste aversion (CTA) to the sugar reinforcer used in the task rather than to mnemonic or motoric impairments. However, by substituting a novel flavored reinforcer (chocolate pellets) prior to the administration of doses of ANI (150 or 210 mg/kg) previously shown to cause amnesia, a strong CTA to chocolate was induced sparing any aversion to sugar. Importantly, when sugar was reintroduced on the following session, we found that memory for the task was not significantly affected by ANI. Thus, these data suggest that memory for a well-learned instrumental response does not require protein synthesis-dependent reconsolidation as a means of long-term maintenance.

Age-dependent effective doses for radionuclides uniformly distributed in air

International Nuclear Information System (INIS)

Hung, Tran Van

2014-01-01

Age-dependent effective doses for external exposure to photons emitted by radionuclides uniformly distributed in air are reported. The calculations were performed for 160 radionuclides, which are important for safety assessment of nuclear facilities. The energies and intensities of photons emitted from radionuclides were taken from the decay data DECDC used for dose calculations. The results are tabulated in the form of effective dose per unit concentration and time (Sv per Bq s m -3 ) for 6 age groups: newborn, 1, 5, 10 and 15 years-old and adult. The effective doses for the adult are also compared to values given in the literature.

Effects of Intranasal Oxytocin on Long-Term Memory in Healthy Humans: A Systematic Review.

Science.gov (United States)

Brambilla, Michela; Manenti, Rosa; de Girolamo, Giovanni; Adenzato, Mauro; Bocchio-Chiavetto, Luisella; Cotelli, Maria

2016-12-01

Preclinical Research The neuropeptide oxytocin (Oxt) is implicated in complex emotional and social behaviors and appears to play an important role in learning and memory. Animal studies have shown that the effects of exogenous Oxt on memory vary according to the timing of administration, context, gender, and dose and may improve the memory of social, but not nonsocial stimuli. Oxt is intimately involved in a broad array of neuropsychiatric functions and may therefore be a pharmacological target for several psychiatric disorders. This review summarizes the potential effects of Oxt on long-term memory processes in healthy humans based on a PubMed search over the period 1980-2016. The effects of intranasal Oxt on human memory are controversial and the studies included in this review have applied a variety of learning paradigms, in turn producing variable outcomes. Specifically, data on the long-term memory of nonemotional stimuli found no effect or even worsening in memory, while studies using emotional stimuli showed an improvement of long-term memory performance. In conclusion, this review identified a link between long-term memory performance and exogenous intranasal Oxt in humans, although these results still warrant further confirmation in large, multicenter randomized controlled trials. Drug Dev Res 77 : 479-488, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Long-term follow-up of low-dose external pituitary irradiation for Cushing's disease

International Nuclear Information System (INIS)

Littley, M.D.; Shalet, S.M.; Beardwell, C.G.; Ahmed, S.R.; Sutton, M.L.

1990-01-01

Twenty-four patients (three male) with Cushing's disease, aged between 11 and 67 years, were treated with low-dose external pituitary irradiation (20 Gy in eight fractions over 10-12 days) and followed for between 13 and 171 months (median 93 months). Eleven patients (46%) went into remission 4-36 months after irradiation, but five subsequently relapsed. In this series, the low incidence of radiation-induced hypopituitarism and absence of other complications attributable to radiotherapy suggest that low-dose pituitary irradiation may be a useful treatment option in selected patients. However, long-term follow-up has demonstrated a high relapse rate and failure to prevent Nelson's syndrome in adrenalectomized patients, indicating that it should not be used as primary treatment in preference to selective adenomectomy. (author)

Dose rate effect models for biological reaction to ionizing radiation in human cell lines

International Nuclear Information System (INIS)

Magae, Junji; Ogata, Hiromitsu

2008-01-01

Full text: Because of biological responses to ionizing radiation are dependent on irradiation time or dose rate as well as dose, simultaneous inclusion of dose and dose rate is required to evaluate the risk of long term irradiation at low dose rates. We previously published a novel statistical model for dose rate effect, modified exponential (MOE) model, which predicts irradiation time-dependent biological response to low dose rate ionizing radiation, by analyzing micronucleus formation and growth inhibition in a human osteosarcoma cell line, exposed to wide range of doses and dose rates of gamma-rays. MOE model demonstrates that logarithm of median effective dose exponentially increases in low dose rates, and thus suggests that the risk approaches to zero at infinitely low dose rate. In this paper, we extend the analysis in various kinds of human cell lines exposed to ionizing radiation for more than a year. We measured micronucleus formation and [ 3 H]thymidine uptake in human cell lines including an osteosarcoma, a DNA-dependent protein kinase-deficient glioma, a SV40-transformed fibroblast derived from an ataxia telangiectasia patient, a normal fibroblast, and leukemia cell lines. Cells were exposed to gamma-rays in irradiation room bearing 50,000 Ci of cobalt-60. After the irradiation, they were cultured for 24 h in the presence of cytochalasin B to block cytokinesis, and cytoplasm and nucleus were stained with DAPI and prospidium iodide. The number of binuclear cells bearing a micronucleus was counted under a fluorescence microscope. For proliferation inhibition, cells were cultured for 48 h after the irradiation and [ 3 H] thymidine was pulsed for 4 h before harvesting. We statistically analyzed the data for quantitative evaluation of radiation risk. While dose and dose rate relationship cultured within one month followed MOE model in cell lines holding wild-type DNA repair system, dose rate effect was greatly impaired in DNA repair-deficient cell lines

Dose and Spatial Effects in Long-Distance Radiation Signaling In Vivo: Implications for Abscopal Tumorigenesis

International Nuclear Information System (INIS)

Mancuso, Mariateresa; Giardullo, Paola; Leonardi, Simona; Pasquali, Emanuela; Casciati, Arianna; De Stefano, Ilaria; Tanori, Mirella; Pazzaglia, Simonetta; Saran, Anna

2013-01-01

Purpose: To investigate the dose and spatial dependence of abscopal radiation effects occurring in vivo in the mouse, along with their tumorigenic potential in the central nervous system (CNS) of a radiosensitive mouse model. Methods and Materials: Patched1 (Ptch1) +/− mice, carrying a germ-line heterozygous inactivating mutation in the Ptch1 gene and uniquely susceptible to radiation damage in neonatal cerebellum, were exposed directly to ionizing radiation (1, 2, or 3 Gy of x-rays) or treated in a variety of partial-body irradiation protocols, in which the animals' head was fully protected by suitable lead cylinders while the rest of the body was exposed to x-rays in full or in part. Apoptotic cell death was measured in directly irradiated and shielded cerebellum shortly after irradiation, and tumor development was monitored in lifetime groups. The same endpoints were measured using different shielding geometries in mice irradiated with 3 or 10 Gy of x-rays. Results: Although dose-dependent cell death was observed in off-target cerebellum for all doses and shielding conditions tested, a conspicuous lack of abscopal response for CNS tumorigenesis was evident at the lowest dose of 1 Gy. By changing the amount of exposed body volume, the shielding geometry could also significantly modulate tumorigenesis depending on dose. Conclusions: We conclude that interplay between radiation dose and exposed tissue volume plays a critical role in nontargeted effects occurring in mouse CNS under conditions relevant to humans. These findings may help understanding the mechanisms of long-range radiation signaling in harmful effects, including carcinogenesis, occurring in off-target tissues

Pulse and integral optically stimulated luminescence (OSL). Similarities and dissimilarities to thermoluminescence (TL) dose dependence and dose-rate effects

International Nuclear Information System (INIS)

Chen, R.; Leung, P.L.

2000-01-01

Optically stimulated luminescence (OSL) and thermoluminescence (Tl) are two possible methods to monitor the absorbed radiation in solid samples, and therefore are utilized for dosimetry. For this application, two properties are desirable, namely, linear dose dependence of the measured quantity and dose-rate independence. For Tl, different kinds of super linear dose dependence have been reported in the literature in different materials, and in some cases, dose-rate dependence has also been found. These have been explained as being the result of competition. In OSL, some recent works reported on super linear dose dependence in annealed samples. In the present work, we explain the possible occurrence of these phenomena in OSL by solving numerically the relevant rate equations governing the process during irradiation, relaxation and read-out (heating or light stimulation). The results show that for short pulse OSL, quadratic dose dependence can be expected when only one trapping state and one kind of recombination center are involved and when the excitation starts with empty traps and centers. With the short pulse OSL, the calculation also reveals a possible dose-rate effect. Under the same circumstances, the area under the OSL curve depends linearly on the dose. The dependence of the whole area under the OSL curve on the dose is shown to be super linear when a disconnected trapping state or radiationless center take part in the process. Also, dose-rate effect can be expected in these cases, although no experimental effect of this sort has been reported so far. In pulse OSL, the analogy is made between the measured intensity and the initial rise range of non-first order Tl, whereas for the total area OSL, there is a nearly full analogy with the dose behavior of the Tl maximum. (Author)

The effect of zinc supplementation of lactating rats on short-term and long-term memory of their male offspring.

Science.gov (United States)

Karami, Mohammad; Ehsanivostacolaee, Simin; Moazedi, Ali Ahmad; Nosrati, Anahita

2013-01-01

In this study the effect of zinc chloride (ZnCl2) administration on the short-term and long-term memory of rats were assessed. We enrolled six groups of adult female and control group of eight Wistar rats in each group. One group was control group with free access to food and water, and five groups drunk zinc chloride in different doses (20, 30, 50, 70 and 100 mg/kg/day) in drinking water for two weeks during lactation .One month after birth, a shuttle box used to short- term and long-term memory and the latency in entering the dark chamber as well. This experiment showed that maternal 70 mg/kg dietary zinc during lactation influenced the working memory of rats' offspring in all groups. Rats received 100 mg/kg/day zinc during lactation so they had significant impairment in working memory (short-term) of their offspring (Plong-term) memory of all groups. Drug consumption below70 mg/kg/day zinc chloride during lactation had no effect. While enhanced 100 mg/ kg/ day zinc in lactating rats could cause short-term memory impairment.

Cystic fibrosis in adults. Short-term and long-term reproducibility of the Brody score for lung morphology in low-dose MDCT scans

Energy Technology Data Exchange (ETDEWEB)

Weber, K.; Paolini, M.; Schmitz, M.; Coppenrath, E.; Reiser, M.; Mueller-Lisse, U.G. [Ludwig-Maximilians-Univ. Muenchen (Germany). Inst. fuer Klinische Radiologie; Fischer, R.; Huber, R. [Ludwig-Maximilians-Univ. Muenchen (Germany). Medical Hospital V

2014-01-15

Purpose: The semi-quantitative Brody score measures the severity of cystic fibrosis (CF)-related lung disease. We investigated the short-term (28 - 60 days) and long-term (2 - 7 years) intra- and inter-observer reproducibility of the Brody score in low-dose multidetector row computed tomography examinations performed in inspiration (LDCTs) of adult CF patients. Materials and Methods: Composite Brody scores and respective underlying bronchiectasis, mucus plugging, peribronchial thickening, parenchymal opacity, and hyperinflation subscores were evaluated twice (time interval, 1 - 84 months) by each of 3 independent radiologists (1 - 20 years of professional diagnostic radiology experience) in LDCTs (4 - 64 rows, 120 KVp, 10 - 15 mAs/slice, CTDIw approx. 1.0 mGy, effective dose approx. 0.5 mSv) of 15 adult patients with CF-related lung disease (8 female, 7 male, age, 18 - 50 years, mean, 33 years). Results: The average reproducibility of the Brody score was within +/-7 % (range, 2 - 30 %) between radiologists, and +/-6 % (3 - 12 %) within radiologists (short-term, 28 - 60 days, 4 %, 0 - 12 %, long-term, 2 - 7 years, 12 %, 1 - 36 %). For the different subscores, the reproducibility was within +/-25 % (15 - 41 %) between radiologists and +/-23 % (12 - 46 %) within radiologists. Conclusion: The Brody score shows high average inter-observer reproducibility in LDCTs of adult CF patients. The Brody score also demonstrates high average intra-observer reproducibility if subsequent assessments are made within 28 - 61 days. With time intervals of 2 - 7 years between subsequent evaluations, however, intra-observer reproducibility decreases. Respective subscores each demonstrate lower intra- and inter-observer reproducibility than does the composite Brody score. (orig.)

Optimal low-dose radiosurgery combined with and without intervention for unruptured arteriovenous malformations. A long-term follow-up study

International Nuclear Information System (INIS)

Inoue, Hiroshi K.; Naitou, Isao

2006-01-01

Treatment indication for unruptured arteriovenous malformations (AVMs) of the brain was investigated based on long-term results of low-dose Gamma Knife (GK) surgery. Thirty-nine patients with unruptured AVMs treated with GK surgery were followed more than 7 years. These AVMs were found due to seizure and steal symptoms in 22 and 4 patients, respectively, and incidentally in 13. Embolization was performed in 6 patients before GK surgery. Total obliteration was obtained in 83.3% after initial treatment and 95.8% after additional treatment. Bleeding before total obliteration occurred in 2 patients and adverse effect on the internal capsule in 1. It is concluded that low-dose GK surgery is safe and effective for the treatment of unruptured AVMs, especially symptomatic AVMs in functional areas. (author)

Short- and long-term cognitive effects of chronic cannabinoids administration in late-adolescence rats.

Directory of Open Access Journals (Sweden)

Hila Abush

Full Text Available The use of cannabis can impair cognitive function, especially short-term memory. A controversial question is whether long-term cannabis use during the late-adolescence period can cause irreversible deficits in higher brain function that persist after drug use stops. In order to examine the short- and long-term effects of chronic exposure to cannabinoids, rats were administered chronic i.p. treatment with the CB1/CB2 receptor agonist WIN55,212-2 (WIN; 1.2 mg/kg for two weeks during the late adolescence period (post-natal days 45-60 and tested for behavioral and electrophysiological measures of cognitive performance 24 hrs, 10 and 30 days after the last drug injection. The impairing effects of chronic WIN on short-term memory in the water maze and the object recognition tasks as well as long-term potentiation (LTP in the ventral subiculum (vSub-nucleus accumbens (NAc pathway were temporary as they lasted only 24 h or 10 d after withdrawal. However, chronic WIN significantly impaired hippocampal dependent short-term memory measured in the object location task 24 hrs, 10, 30, and 75 days after the last drug injection. Our findings suggest that some forms of hippocampal-dependent short-term memory are sensitive to chronic cannabinoid administration but other cognitive impairments are temporary and probably result from a residue of cannabinoids in the brain or acute withdrawal effects from cannabinoids. Understanding the effects of cannabinoids on cognitive function may provide us with tools to overcome these impairments and for cannabinoids to be more favorably considered for clinical use.

Effects of long-term voluntary exercise on learning and memory processes: dependency of the task and level of exercise.

Science.gov (United States)

García-Capdevila, Sílvia; Portell-Cortés, Isabel; Torras-Garcia, Meritxell; Coll-Andreu, Margalida; Costa-Miserachs, David

2009-09-14

The effect of long-term voluntary exercise (running wheel) on anxiety-like behaviour (plus maze and open field) and learning and memory processes (object recognition and two-way active avoidance) was examined on Wistar rats. Because major individual differences in running wheel behaviour were observed, the data were analysed considering the exercising animals both as a whole and grouped according to the time spent in the running wheel (low, high, and very-high running). Although some variables related to anxiety-like behaviour seem to reflect an anxiogenic compatible effect, the view of the complete set of variables could be interpreted as an enhancement of defensive and risk assessment behaviours in exercised animals, without major differences depending on the exercise level. Effects on learning and memory processes were dependent on task and level of exercise. Two-way avoidance was not affected either in the acquisition or in the retention session, while the retention of object recognition task was affected. In this latter task, an enhancement in low running subjects and impairment in high and very-high running animals were observed.

The basic approaches to evaluation of effects of the long-therm radiation exposure in a range of 'low' doses

International Nuclear Information System (INIS)

Takhauov, R.M.; Karpov, A.B.; Litvyakov, N.V.

2010-01-01

The previously performed research allowed forming the main concepts about deterministic effects of radiation impact and defining the main postulates of radiation medicine with respect to average and high levels of exposure. At the same time the research performed to evaluate stochastic effects caused by 'low' doses of ionizing radiation influence failed to find a single-valued answer relating both to dose impact inducing the effect development and to the spectrum of recorded pathologic processes or diseases. In this connection on our opinion the most prospective decision of present problem are studies in follow directions: 1. The evaluation of radiation productions personal and residents of nearby territories mortality and morbidity structure and dynamics. 2. The estimation of risk main diseases development with long-term radiation exposure and analysis of radiation factor role in its pathogenesis. 3. The study of genetic disturbances of persons and their descendants exposed long-term ionizing radiation in 'low' doses. 4. The study of individual radio sensitivity genetic markers. 5. The evaluation of structural and functional homeostasis disturbances inducing the radiation exposure in 'low' doses. The object of study is the Close administrative territorial formation Seversk population and mainly Siberian Group Chemical Enterprises (SGCE) personal - the largest complex productions of atomic industry in the world. The Regional Medico-Dosimetric Register (RMDR), creating since 2001 is the basis for epidemiological studies. The register database contain the information concerning to about 66 000 SGCE workers (it is a whole number of workers in all years of SGCE existence from 1950 to now day). The 35 000 from 66 000 workers are the workers of so-called main productions. About 96% workers exposed external radiation has cumulative dose less 500 mSv. On the base of laboratory of genomic medicine it was created and constantly enriched the bank DNA and biological material

Estimation of effective dose from the atmospheric nuclear tests due to the intake of marine products

International Nuclear Information System (INIS)

Nakano, Masanao

2008-01-01

The worldwide environmental protection is required by the public. A long-term environmental assessment from nuclear fuel cycle facilities to the aquatic environment also becomes more important to understand long-term risk of nuclear energy. Evaluation of long-term risk including not only in Japan but also in neighboring countries is considered to be necessary in order to develop sustainable nuclear power industry. The author successfully simulated the distribution of radionuclides in seawater and seabed sediment produced by atmospheric nuclear tests using LAMER (Long-term Assessment ModEl of Radionuclides in the oceans). A part of the LAMER calculated the advection-diffusion-scavenging processes for radionuclides in the oceans and the Japan Sea in cooperate with Oceanic General Circulation Model (OGCM) and was validated. The author is challenging to calculate probabilistic effective dose suggested by ICRP from intake of marine products due to atmospheric nuclear tests using the Monte Carlo method in the other part of LAMER. Depending on the deviation of each parameter, the 95th percentile of the probabilistic effective dose was from one third to two thirds of the 95th percentile of the deterministic effective dose in proforma calculation. It means that probabilistic assessment can contribute to the design and optimisation of a nuclear fuel cycle facility. (author)

Long Term assessment of the dose registered by the Sanitary workers of a mutual

International Nuclear Information System (INIS)

Anies Escartin, J.; Perramon Llado, A.

2004-01-01

The analysis of a long time period of time (about 17 years) of the professional exposure to ionising radiation of the workers of an accidents Mutual, that has its own personal Dosimetry Service, allows to establish a relation between the showed global reduction of the registered doses of the people exposed and the circumstances and actions that did it possible. The fact to carry out a dosimetric control is an essential factor directed to accomplish the objective of holding the doses as low as achievable, joined with the fact of passing more strict law. Those factors that fixed a reduction of the doses inherited by the sanitary exposed workers whose relation are demonstrated in this study. The collective dose inherited by the bunch of people exposed is the parameter suitable to measure and assess the time history at medium and long term of the exposure conditions of the workers, and identify the more relevant characteristics of the risk by ionising radiation at workplace. The conclusion of the time history analysis of the quantity shows that the total collective dose for more than a thousand people group, are strongly affected by the doses corresponding to less than a 1,5 % of the users. The number of people that have a value dose higher that the average, and the high value of the dose in some periods because of their activity lead to changes of the value of the collective doses that can be higher than 100%. This great uncertainty in the measured value needs more than ten months of control to guarantee the lowering of doses received. The decreasing doses observed are strongly related with the reduction of this relative short number of cases with incidences in the doses registered. An important part of the work is related to identifying the incidences registered, noticing the evolution and checking the most suitable actions to lower it. (Author) 4 refs

Calculation of age-dependent effective doses for external exposure using the MCNP code

International Nuclear Information System (INIS)

Hung, Tran Van

2013-01-01

Age-dependent effective dose for external exposure to photons uniformly distributed in air were calculated. Firstly, organ doses were calculated with a series of age-specific MIRD-5 type phantoms using the Monte Carlo code MCNP. The calculations were performed for mono-energetic photon sources with source energies from 10 keV to 5 MeV and for phantoms of newborn, 1, 5, 10, and 15 years-old and adult. Then, the effective doses to the different age-phantoms from the mono-energetic photon sources were estimated based on the obtained organ doses. From the calculated results, it is shown that the effective doses depend on the body size; the effective doses in younger phantoms are higher than those in the older phantoms, especially below 100 keV. (orig.)

Calculation of age-dependent effective doses for external exposure using the MCNP code

Energy Technology Data Exchange (ETDEWEB)

Hung, Tran Van [Research and Development Center for Radiation Technology, ThuDuc, HoChiMinh City (VT)

2013-07-15

Age-dependent effective dose for external exposure to photons uniformly distributed in air were calculated. Firstly, organ doses were calculated with a series of age-specific MIRD-5 type phantoms using the Monte Carlo code MCNP. The calculations were performed for mono-energetic photon sources with source energies from 10 keV to 5 MeV and for phantoms of newborn, 1, 5, 10, and 15 years-old and adult. Then, the effective doses to the different age-phantoms from the mono-energetic photon sources were estimated based on the obtained organ doses. From the calculated results, it is shown that the effective doses depend on the body size; the effective doses in younger phantoms are higher than those in the older phantoms, especially below 100 keV. (orig.)

Review of proton pump inhibitors for the initial treatment of heartburn: is there a dose ceiling effect?

Science.gov (United States)

Kushner, Pamela R; Peura, David A

2011-05-01

Proton pump inhibitors (PPIs) are widely used in clinical practice. However, concerns have been expressed about their long-term use, particularly with regard to bone health, Clostridium difficile infections, and drug interactions with platelet aggregation inhibitors. There has been limited guidance for clinicians concerning appropriate dose selection of PPIs for the initial treatment of heartburn. This review explored whether published clinical trials provide evidence of a ceiling above which higher PPI doses do not provide additional clinical benefit over the lowest approved dose. All articles of randomized, controlled clinical trials in nonerosive gastroesophageal reflux disease (GERD) in which the effects of two or more doses of the same PPI on symptomatic relief of heartburn were quantified as a study endpoint were identified and analyzed through PubMed searches up to the end of September 2010. The majority of trials evaluated provided no evidence that higher PPI doses were superior to the lowest approved dose for the initial treatment of heartburn. There were no clinically relevant findings with respect to dose dependence and safety outcomes in these studies. Efficacy outcomes from the trials suggest there may be a dose ceiling effect and highlight the need for further research on the use of the lowest effective PPI doses as an appropriate strategy in the initial treatment of uncomplicated heartburn. Observational studies and some meta-analyses have suggested that long-term PPI pharmacotherapy might be associated with safety concerns, which necessitate the periodic evaluation of therapeutic benefit in terms of symptom resolution and regimen tolerability. However, evidence to date suggests that use of the lowest effective dose for the indication is not associated with significant adverse events, particularly in the short term. Clinical practice suggests that patients requiring long-term treatment should be maintained on the lowest dose necessary to control

Long-term effects of a preoperative smoking cessation programme

DEFF Research Database (Denmark)

Villebro, Nete Munk; Pedersen, Tom; Møller, Ann M

2008-01-01

Preoperative smoking intervention programmes reduce post-operative complications in smokers. Little is known about the long-term effect upon smoking cessation.......Preoperative smoking intervention programmes reduce post-operative complications in smokers. Little is known about the long-term effect upon smoking cessation....

Long term effects of radiation in man

International Nuclear Information System (INIS)

Tso Chih Ping; Idris Besar

1984-01-01

An overview of the long term effects of radiation in man is presented, categorizing into somatic effects, genetic effects and teratogenic effects, and including an indication of the problems that arise in their determination. (author)

Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial

NARCIS (Netherlands)

Y. van Pareren; M. Houdijk; M. Jansen (Maarten); M. Reeser; P.G.H. Mulder (Paul); A.C.S. Hokken-Koelega (Anita)

2003-01-01

textabstractThe GH dose-response effect of long-term continuous GH treatment on adult height (AH) was evaluated in 54 short children born small for gestational age (SGA) who were participating in a randomized, double-blind, dose-response trial. Patients were randomly and blindly

Successful treatment of dwarfism secondary to long-term steroid therapy in steroid-dependent nephrotic syndrome.

Science.gov (United States)

Sun, Linlin; Chen, Dongping; Zhao, Xuezhi; Xu, Chenggang; Mei, Changlin

2010-01-01

Prolonged steroid therapy is generally used for steroid-dependent nephrotic syndrome in pediatric patients. However, dwarfism secondary to a long-term regimen and its successful reverse is rarely reported. The underlying mechanism of dwarfism is still poorly understood, as both long-term steroid use and nephrotic syndrome may interact or independently interfere with the process of growth. Here, we present a 17-year-old patient with dwarfism and steroid-dependent nephrotic syndrome and the successful treatment by recombinant human growth factor and cyclosporine A with withdrawal of steroid. We also briefly review the current understanding and the management of dwarfism in pediatric patients with nephrotic syndrome.

Long-term effects of ionizing radiation

International Nuclear Information System (INIS)

Kaul, Alexander; Burkart, Werner; Grosche, Bernd; Jung, Thomas; Martignoni, Klaus; Stephan, Guenther

1997-01-01

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

Population pharmacokinetic model of THC integrates oral, intravenous, and pulmonary dosing and characterizes short- and long-term pharmacokinetics.

Science.gov (United States)

Heuberger, Jules A A C; Guan, Zheng; Oyetayo, Olubukayo-Opeyemi; Klumpers, Linda; Morrison, Paul D; Beumer, Tim L; van Gerven, Joop M A; Cohen, Adam F; Freijer, Jan

2015-02-01

Δ(9)-Tetrahydrocannobinol (THC), the main psychoactive compound of Cannabis, is known to have a long terminal half-life. However, this characteristic is often ignored in pharmacokinetic (PK) studies of THC, which may affect the accuracy of predictions in different pharmacologic areas. For therapeutic use for example, it is important to accurately describe the terminal phase of THC to describe accumulation of the drug. In early clinical research, the THC challenge test can be optimized through more accurate predictions of the dosing sequence and the wash-out between occasions in a crossover setting, which is mainly determined by the terminal half-life of the compound. The purpose of this study is to better quantify the long-term pharmacokinetics of THC. A population-based PK model for THC was developed describing the profile up to 48 h after an oral, intravenous, and pulmonary dose of THC in humans. In contrast to earlier models, the current model integrates all three major administration routes and covers the long terminal phase of THC. Results show that THC has a fast initial and intermediate half-life, while the apparent terminal half-life is long (21.5 h), with a clearance of 38.8 L/h. Because the current model characterizes the long-term pharmacokinetics, it can be used to assess the accumulation of THC in a multiple-dose setting and to forecast concentration profiles of the drug under many different dosing regimens or administration routes. Additionally, this model could provide helpful insights into the THC challenge test used for the development of (novel) compounds targeting the cannabinoid system for different therapeutic applications and could improve decision making in future clinical trials.

Methylprednisolone as a memory enhancer in rats: Effects on aversive memory, long-term potentiation and calcium influx.

Science.gov (United States)

de Vargas, Liane da Silva; Gonçalves, Rithiele; Lara, Marcus Vinícius S; Costa-Ferro, Zaquer S M; Salamoni, Simone Denise; Domingues, Michelle Flores; Piovesan, Angela Regina; de Assis, Dênis Reis; Vinade, Lucia; Corrado, Alexandre P; Alves-Do-Prado, Wilson; Correia-de-Sá, Paulo; da Costa, Jaderson Costa; Izquierdo, Ivan; Dal Belo, Cháriston A; Mello-Carpes, Pâmela B

2017-09-01

It is well recognized that stress or glucocorticoids hormones treatment can modulate memory performance in both directions, either impairing or enhancing it. Despite the high number of studies aiming at explaining the effects of glucocorticoids on memory, this has not yet been completely elucidated. Here, we demonstrate that a low daily dose of methylprednisolone (MP, 5mg/kg, i.p.) administered for 10-days favors aversive memory persistence in adult rats, without any effect on the exploring behavior, locomotor activity, anxiety levels and pain perception. Enhanced performance on the inhibitory avoidance task was correlated with long-term potentiation (LTP), a phenomenon that was strengthen in hippocampal slices of rats injected with MP (5mg/kg) during 10days. Additionally, in vitro incubation with MP (30-300µM) concentration-dependently increased intracellular [Ca 2+ ] i in cultured hippocampal neurons depolarized by KCl (35mM). In conclusion, a low daily dose of MP for 10days may promote aversive memory persistence in rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Phosphodiesterase 10A inhibition attenuates sleep deprivation-induced deficits in long-term fear memory.

Science.gov (United States)

Guo, Lengqiu; Guo, Zhuangli; Luo, Xiaoqing; Liang, Rui; Yang, Shui; Ren, Haigang; Wang, Guanghui; Zhen, Xuechu

2016-12-02

Sleep, particularly rapid eye movement (REM) sleep, is implicated in the consolidation of emotional memories. In the present study, we investigated the protective effects of a phosphodiesterase 10A (PDE10A) inhibitor MP-10 on deficits in long-term fear memory induced by REM sleep deprivation (REM-SD). REM-SD caused deficits in long-term fear memory, however, MP-10 administration ameliorated the deleterious effects of REM-SD on long term fear memory. Brain-derived neurotropic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) were altered in specific brain regions associated with learning and memory in REM-SD rats. Accordingly, REM-SD caused a significant decrease of pCREB in hippocampus and striatum and a significant decrease of BDNF in the hippocampus, striatum and amygdala, however, MP-10 reversed the effects of REM-SD in a dose-dependent manner. Our findings suggest that REM-SD disrupts the consolidation of long-term fear memory and that administration of MP-10 protects the REM-SD-induced deficits in fear memory, which may be due to the MP-10-induced expression of BDNF in the hippocampus, striatum and amygdala, and phosphorylation of CREB in the hippocampus and striatum. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of short-term heart rate variability biofeedback on long-term abstinence in alcohol dependent patients - a one-year follow-up.

Science.gov (United States)

Penzlin, Ana Isabel; Barlinn, Kristian; Illigens, Ben Min-Woo; Weidner, Kerstin; Siepmann, Martin; Siepmann, Timo

2017-09-06

A randomized controlled study (RCT) recently showed that short-term heart rate variability (HRV) biofeedback in addition to standard rehabilitation care for alcohol dependence can reduce craving, anxiety and improve cardiovascular autonomic function. In this one-year follow-up study we aimed to explore whether completion of 2-week HRV-Biofeedback training is associated with long-term abstinence. Furthermore, we sought to identify potential predictors of post-treatment abstinence. We conducted a survey on abstinence in patients with alcohol dependence 1 year after completion of an RCT comparing HRV-biofeedback in addition to inpatient rehabilitation treatment alone (controls). Abstinence rates were compared and analysed for association with demographic data as well as psychometric and autonomic cardiac assessment before and after completion of the biofeedback training using bivariate and multivariate regression analyses. Out of 48 patients who participated in the RCT, 27 patients (9 females, ages 42.9 ± 8.6, mean ± SD) completed our one-year follow-up. When including in the analysis only patients who completed follow-up, the rate of abstinence tended to be higher in patients who underwent HRV-biofeedback 1 year earlier compared to those who received rehabilitative treatment alone (66.7% vs 50%, p = ns). This non-significant trend was also observed in the intention-to-treat analysis where patients who did not participate in the follow-up were assumed to have relapsed (46,7% biofeedback vs. 33.3% controls, p = ns). Neither cardiac autonomic function nor psychometric variables were associated with abstinence 1 year after HRV-biofeedback. Our follow-up study provide a first indication of possible increase in long-term abstinence after HRV-biofeedback for alcohol dependence in addition to rehabilitation. The original randomized controlled trial was registered in the German Clinical Trials Register ( DRKS00004618 ). This one-year follow-up survey has not been

Effects of trawl selectivity and genetic parameters on fish body length under long-term trawling

Science.gov (United States)

Yu, Yang; Sun, Peng; Cui, He; Sheng, Huaxiang; Zhao, Fenfang; Tang, Yanli; Chen, Zelin

2015-10-01

Long-term fishing pressure affects the biological characteristics of exploited fish stocks. The biological characteristics of hairtail ( Trichiurus lepturus) in the East China Sea are unable to recover because of long-term trawling. Fishing induces evolutionary effects on the fish's biological characteristics. Evidence of these changes includes small size at age, a shift to earlier age structure, and early maturation. Natural and artificial selection usually affect the fish's life history. Selection can induce different chances of reproduction, and individual fish can give a different genetic contribution to the next generation. In this study, analysis of time-dependent probability of significance and test of sensitivity were used to explore the effects of fish exploitation rate, mesh size, and heritability with long-term trawling. Results showed that fishing parameters were important drivers to exploited fish population. However, genetic traits altered by fishing were slow, and the changes in biological characteristics were weaker than those caused by fishing selection. Exploitation rate and mesh size exhibited similar evolutionary trend tendency under long-term fishing. The time-dependent probability of significance trend showed a gradual growth and tended to be stable. Therefore, the direction of fishing-induced evolution and successful management of fish species require considerable attention to contribute to sustainable fisheries in China.

A unique role of the cholera toxin A1-DD adjuvant for long-term plasma and memory B cell development.

Science.gov (United States)

Bemark, Mats; Bergqvist, Peter; Stensson, Anneli; Holmberg, Anna; Mattsson, Johan; Lycke, Nils Y

2011-02-01

Adjuvants have traditionally been appreciated for their immunoenhancing effects, whereas their impact on immunological memory has largely been neglected. In this paper, we have compared three mechanistically distinct adjuvants: aluminum salts (Alum), Ribi (monophosphoryl lipid A), and the cholera toxin A1 fusion protein CTA1-DD. Their influence on long-term memory development was dramatically different. Whereas a single immunization i.p. with 4-hydroxy-3-nitrophenyl acetyl (NP)-chicken γ-globulin and adjuvant stimulated serum anti-NP IgG titers that were comparable at 5 wk, CTA1-DD-adjuvanted responses were maintained for >16 mo with a half-life of anti-NP IgG ∼36 wk, but DD dose-dependent increase in germinal center (GC) size and numbers was found, with >60% of splenic B cell follicles hosting GC at an optimal CTA1-DD dose. Roughly 7% of these GC were NP specific. This GC-promoting effect correlated well with the persistence of long-term plasma cells in the bone marrow and memory B cells in the spleen. CTA1-DD also facilitated increased somatic hypermutation and affinity maturation of NP-specific IgG Abs in a dose-dependent fashion, hence arguing that large GC not only promotes higher Ab titers but also high-quality Ab production. Adoptive transfer of splenic CD80(+), but not CD80(-), B cells, at 1 y after immunization demonstrated functional long-term anti-NP IgG and IgM memory cells. To our knowledge, this is the first report to specifically compare and document that adjuvants can differ considerably in their support of long-term immune responses. Differential effects on the GC reaction appear to be the basis for these differences.

Covered interest parity arbitrage and temporal long-term dependence between the US dollar and the Yen

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Batten, Jonathan A.; Szilagyi, Peter G.

2007-03-01

Using a daily time series from 1983 to 2005 of currency prices in spot and forward USD/Yen markets and matching equivalent maturity short-term US and Japanese interest rates, we investigate the sensitivity of the difference between actual prices in forward markets to those calculated from differentials in short-term interest rates. According to a fundamental theorem in financial economics termed covered interest parity (CIP), the actual and estimated prices should be identical once transaction and other costs are accommodated. The paper presents three important findings: first, we find evidence of considerable variation in CIP deviations from equilibrium; second, these deviations have diminished significantly and by 2000 have been almost eliminated; third, an analysis of the CIP deviations using the local Hurst exponent finds episodes of time-varying dependence over the various sample periods, which appear to be linked to episodes of dollar decline/Yen appreciation, or vice versa. The finding of temporal long-term dependence in CIP deviations is consistent with recent evidence of temporal long-term dependence in the returns of currency, stock and commodity markets.

Long-Term Anabolic Androgenic Steroid Use Is Associated with Increased Atrial Electromechanical Delay in Male Bodybuilders

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Mustafa Akçakoyun

2014-01-01

Full Text Available We investigated the effect of long-term supraphysiologic doses of anabolic androgenic steroids (AAS on atrial electromechanical delay (AEMD in male bodybuilders. We clearly demonstrated that long-term consumption of supraphysiologic doses of AAS is associated with higher values of inter- and intra-AEMD in healthy young bodybuilders.

Layer 2/3 synapses in monocular and binocular regions of tree shrew visual cortex express mAChR-dependent long-term depression and long-term potentiation.

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McCoy, Portia; Norton, Thomas T; McMahon, Lori L

2008-07-01

Acetylcholine is an important modulator of synaptic efficacy and is required for learning and memory tasks involving the visual cortex. In rodent visual cortex, activation of muscarinic acetylcholine receptors (mAChRs) induces a persistent long-term depression (LTD) of transmission at synapses recorded in layer 2/3 of acute slices. Although the rodent studies expand our knowledge of how the cholinergic system modulates synaptic function underlying learning and memory, they are not easily extrapolated to more complex visual systems. Here we used tree shrews for their similarities to primates, including a visual cortex with separate, defined regions of monocular and binocular innervation, to determine whether mAChR activation induces long-term plasticity. We find that the cholinergic agonist carbachol (CCh) not only induces long-term plasticity, but the direction of the plasticity depends on the subregion. In the monocular region, CCh application induces LTD of the postsynaptic potential recorded in layer 2/3 that requires activation of m3 mAChRs and a signaling cascade that includes activation of extracellular signal-regulated kinase (ERK) 1/2. In contrast, layer 2/3 postsynaptic potentials recorded in the binocular region express long-term potentiation (LTP) following CCh application that requires activation of m1 mAChRs and phospholipase C. Our results show that activation of mAChRs induces long-term plasticity at excitatory synapses in tree shrew visual cortex. However, depending on the ocular inputs to that region, variation exists as to the direction of plasticity, as well as to the specific mAChR and signaling mechanisms that are required.

Home or foster home care versus institutional long-term care for functionally dependent older people.

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Young, Camilla; Hall, Amanda M; Gonçalves-Bradley, Daniela C; Quinn, Terry J; Hooft, Lotty; van Munster, Barbara C; Stott, David J

2017-04-03

Changing population demographics have led to an increasing number of functionally dependent older people who require care and medical treatment. In many countries, government policy aims to shift resources into the community from institutional care settings with the expectation that this will reduce costs and improve the quality of care compared. To assess the effects of long-term home or foster home care versus institutional care for functionally dependent older people. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Library, MEDLINE, Embase, CINAHL, and two trials registers to November 2015. We included randomised and non-randomised trials, controlled before-after studies and interrupted time series studies complying with the EPOC study design criteria and comparing the effects of long-term home care versus institutional care for functionally dependent older people. Two reviewers independently extracted data and assessed the risk of bias of each included study. We reported the results narratively, as the substantial heterogeneity across studies meant that meta-analysis was not appropriate. We included 10 studies involving 16,377 participants, all of which were conducted in high income countries. Included studies compared community-based care with institutional care (care homes). The sample size ranged from 98 to 11,803 (median N = 204). There was substantial heterogeneity in the healthcare context, interventions studied, and outcomes assessed. One study was a randomised trial (N = 112); other included studies used designs that had potential for bias, particularly due lack of randomisation, baseline imbalances, and non-blinded outcome assessment. Most studies did not select (or exclude) participants for any specific disease state, with the exception of one study that only included patients if they had a stroke. All studies had methodological limitations, so readers should interpret results with caution.It is uncertain

Prospective memory deficits in illicit polydrug users are associated with the average long-term typical dose of ecstasy typically consumed in a single session.

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Gallagher, Denis T; Hadjiefthyvoulou, Florentia; Fisk, John E; Montgomery, Catharine; Robinson, Sarita J; Judge, Jeannie

2014-01-01

Neuroimaging evidence suggests that ecstasy-related reductions in SERT densities relate more closely to the number of tablets typically consumed per session rather than estimated total lifetime use. To better understand the basis of drug related deficits in prospective memory (p.m.) we explored the association between p.m. and average long-term typical dose and long-term frequency of use. Study 1: Sixty-five ecstasy/polydrug users and 85 nonecstasy users completed an event-based, a short-term and a long-term time-based p.m. task. Study 2: Study 1 data were merged with outcomes on the same p.m. measures from a previous study creating a combined sample of 103 ecstasy/polydrug users, 38 cannabis-only users, and 65 nonusers of illicit drugs. Study 1: Ecstasy/polydrug users had significant impairments on all p.m. outcomes compared with nonecstasy users. Study 2: Ecstasy/polydrug users were impaired in event-based p.m. compared with both other groups and in long-term time-based p.m. compared with nonillicit drug users. Both drug using groups did worse on the short-term time-based p.m. task compared with nonusers. Higher long-term average typical dose of ecstasy was associated with poorer performance on the event and short-term time-based p.m. tasks and accounted for unique variance in the two p.m. measures over and above the variance associated with cannabis and cocaine use. The typical ecstasy dose consumed in a single session is an important predictor of p.m. impairments with higher doses reflecting increasing tolerance giving rise to greater p.m. impairment.

Divergent short- and long-term effects of acute stress in object recognition memory are mediated by endogenous opioid system activation.

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Nava-Mesa, Mauricio O; Lamprea, Marisol R; Múnera, Alejandro

2013-11-01

Acute stress induces short-term object recognition memory impairment and elicits endogenous opioid system activation. The aim of this study was thus to evaluate whether opiate system activation mediates the acute stress-induced object recognition memory changes. Adult male Wistar rats were trained in an object recognition task designed to test both short- and long-term memory. Subjects were randomly assigned to receive an intraperitoneal injection of saline, 1 mg/kg naltrexone or 3 mg/kg naltrexone, four and a half hours before the sample trial. Five minutes after the injection, half the subjects were submitted to movement restraint during four hours while the other half remained in their home cages. Non-stressed subjects receiving saline (control) performed adequately during the short-term memory test, while stressed subjects receiving saline displayed impaired performance. Naltrexone prevented such deleterious effect, in spite of the fact that it had no intrinsic effect on short-term object recognition memory. Stressed subjects receiving saline and non-stressed subjects receiving naltrexone performed adequately during the long-term memory test; however, control subjects as well as stressed subjects receiving a high dose of naltrexone performed poorly. Control subjects' dissociated performance during both memory tests suggests that the short-term memory test induced a retroactive interference effect mediated through light opioid system activation; such effect was prevented either by low dose naltrexone administration or by strongly activating the opioid system through acute stress. Both short-term memory retrieval impairment and long-term memory improvement observed in stressed subjects may have been mediated through strong opioid system activation, since they were prevented by high dose naltrexone administration. Therefore, the activation of the opioid system plays a dual modulating role in object recognition memory. Copyright © 2013 Elsevier Inc. All rights

Effects of a dietary intervention on gastrointestinal symptoms after prostate cancer radiotherapy: Long-term results from a randomized controlled trial

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Pettersson, Anna; Nygren, Peter; Persson, Christina; Berglund, Anders; Turesson, Ingela; Johansson, Birgitta

2014-01-01

Background and purpose: To evaluate the long-term effects of dietary intervention on gastrointestinal symptoms after highly dose-escalated radiotherapy for localized prostate cancer, using boost with protons or high-dose-rate brachytherapy. Materials and methods: Patients were randomized to an intervention group (n = 64) advised to reduce insoluble dietary fiber and lactose intake, or to a standard care group (n = 66) advised to continue their usual diet. Gastrointestinal symptoms, other domains of health-related quality of life (HRQOL), and dietary intake were evaluated for ⩽24 months post-radiotherapy with the European Organization for Research and Treatment of Cancer quality-of-life questionnaires QLQ-C30 and QLQ-PR25, Gastrointestinal Side Effects Questionnaire, and Food Frequency Questionnaire. The effect of the intervention on gastrointestinal symptoms was evaluated using generalized estimating equations. Results: Dietary intervention had no obvious effect on long-term gastrointestinal symptoms or HRQOL. The intervention group markedly reduced their dietary fiber and lactose intake during radiotherapy, but adherence tended to decline over time. The vast majority of long-term gastrointestinal symptoms were reported as ‘a little’, with a noticeable difference from pre-treatment only for unintentional stool leakage, limitations on daily activities, and mucus discharge. Conclusion: Long-term gastrointestinal symptoms were predominantly mild, and dietary intervention was not superior to a usual diet in preventing these symptoms

Glucose effects on long-term memory performance: duration and domain specificity.

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Owen, Lauren; Finnegan, Yvonne; Hu, Henglong; Scholey, Andrew B; Sünram-Lea, Sandra I

2010-08-01

Previous research has suggested that long-term verbal declarative memory is particularly sensitive to enhancement by glucose loading; however, investigation of glucose effects on certain memory domains has hitherto been neglected. Therefore, domain specificity of glucose effects merits further elucidation. The aim of the present research was to provide a more comprehensive investigation of the possible effects of glucose administration on different aspects of memory by 1) contrasting the effect of glucose administration on different memory domains (implicit/explicit memory; verbal/non-verbal memory, and recognition/familiarity processes), 2) investigating whether potential effects on memory domains differ depending on the dose of glucose administered (25 g versus 60 g), 3) exploring the duration of the glucose facilitation effect (assessment of memory performance 35 min and 1 week after encoding). A double-blind between-subjects design was used to test the effects of administration of 25 and 60 g glucose on memory performance. Implicit memory was improved following administration of 60 g of glucose. Glucose supplementation failed to improve face recognition performance but significantly improved performance of word recall and recognition following administration of 60 g of glucose. However, effects were not maintained 1 week following encoding. Improved implicit memory performance following glucose administration has not been reported before. Furthermore, the current data tentatively suggest that level of processing may determine the required glucose dosage to demonstrate memory improvement and that higher dosages may be able to exert effects on memory pertaining to both hippocampal and non-hippocampal brain regions.

Long-term and short-term action-effect links and their impact on effect monitoring.

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Wirth, Robert; Steinhauser, Robert; Janczyk, Markus; Steinhauser, Marco; Kunde, Wilfried

2018-04-23

People aim to produce effects in the environment, and according to ideomotor theory, actions are selected and executed via anticipations of their effects. Further, to ensure that an action has been successful and an effect has been realized, we must be able to monitor the consequences of our actions. However, action-effect links might vary between situations, some might apply for a majority of situations, while others might only apply to special occasions. With a combination of behavioral and electrophysiological markers, we show that monitoring of self-produced action effects interferes with other tasks, and that the length of effect monitoring is determined by both, long-term action-effect links that hold for most situations, and short-term action-effect links that emerge from a current setting. Effect monitoring is fast and frugal when these action-effect links allow for valid anticipation of action effects, but otherwise effect monitoring takes longer and delays a subsequent task. Specific influences of long-term and short-term links on the P1/N1 and P3a further allow to dissect the temporal dynamics of when these links interact for the purpose of effect monitoring. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Target-Dependent Structural Changes Accompanying Long-Term Synaptic Facilitation in Aplysia Neurons

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Glanzman, David L.; Kandel, Eric R.; Schacher, Samuel

1990-08-01

The mechanisms underlying structural changes that accompany learning and memory have been difficult to investigate in the intact nervous system. In order to make these changes more accessible for experimental analysis, dissociated cell culture and low-light-level video microscopy were used to examine Aplysia sensory neurons in the presence or absence of their target cells. Repeated applications of serotonin, a facilitating transmitter important in behavioral dishabituation and sensitization, produced growth of the sensory neurons that paralleled the long-term enhancement of synaptic strength. This growth required the presence of the postsynaptic motor neuron. Thus, both the structural changes and the synaptic facilitation of Aplysia sensorimotor synapses accompanying long-term behavioral sensitization can be produced in vitro by applying a single facilitating transmitter repeatedly. These structural changes depend on an interaction of the presynaptic neuron with an appropriate postsynaptic target.

Effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation depend on treatment dose, treatment duration and meal contents

International Nuclear Information System (INIS)

Arakawa, Masayuki; Ebato, Chie; Mita, Tomoya; Hirose, Takahisa; Kawamori, Ryuzo; Fujitani, Yoshio; Watada, Hirotaka

2009-01-01

Beta-cell proliferation is regulated by various metabolic demands including peripheral insulin resistance, obesity, and hyperglycemia. In addition to enhancement of glucose-induced insulin secretion, agonists for glucagon-like peptide-1 receptor (GLP-1R) stimulate proliferation and inhibit apoptosis of beta-cells, thereby probably preserve beta-cell mass. To evaluate the beta-cell preserving actions of GLP-1R agonists, we assessed the acute and chronic effects of exendin-4 on beta-cell proliferation, mass and glucose tolerance in C57BL/6J mice under various conditions. Short-term administration of high-dose exendin-4 transiently stimulated beta-cell proliferation. Comparative transcriptomic analysis showed upregulation of IGF-1 receptor and its downstream effectors in islets. Treatment of mice with exendin-4 daily for 4 weeks (long-term administration) and feeding high-fat diet resulted in significant inhibition of weight gain and improvement of glucose tolerance with reduced insulin secretion and beta-cell mass. These findings suggest that long-term GLP-1 treatment results in insulin sensitization of peripheral organs, rather than enhancement of beta-cell proliferation and function, particularly when animals are fed high-fat diet. Thus, the effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation largely depend on treatment dose, duration of treatment and meal contents. While GLP-1 enhances proliferation of beta-cells in some diabetic mice models, our results suggest that GLP-1 stimulates beta-cell growth only when expansion of beta-cell mass is required to meet metabolic demands.

Effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation depend on treatment dose, treatment duration and meal contents

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Arakawa, Masayuki; Ebato, Chie; Mita, Tomoya [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Hirose, Takahisa [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University School of Medicine, Tokyo (Japan); Kawamori, Ryuzo [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University School of Medicine, Tokyo (Japan); Center for Beta Cell Biology and Regeneration, Juntendo University School of Medicine, Tokyo (Japan); Sportology Center, Juntendo University School of Medicine, Tokyo (Japan); Fujitani, Yoshio, E-mail: fujitani@juntendo.ac.jp [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University School of Medicine, Tokyo (Japan); Watada, Hirotaka, E-mail: hwatada@juntendo.ac.jp [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Sportology Center, Juntendo University School of Medicine, Tokyo (Japan)

2009-12-18

Beta-cell proliferation is regulated by various metabolic demands including peripheral insulin resistance, obesity, and hyperglycemia. In addition to enhancement of glucose-induced insulin secretion, agonists for glucagon-like peptide-1 receptor (GLP-1R) stimulate proliferation and inhibit apoptosis of beta-cells, thereby probably preserve beta-cell mass. To evaluate the beta-cell preserving actions of GLP-1R agonists, we assessed the acute and chronic effects of exendin-4 on beta-cell proliferation, mass and glucose tolerance in C57BL/6J mice under various conditions. Short-term administration of high-dose exendin-4 transiently stimulated beta-cell proliferation. Comparative transcriptomic analysis showed upregulation of IGF-1 receptor and its downstream effectors in islets. Treatment of mice with exendin-4 daily for 4 weeks (long-term administration) and feeding high-fat diet resulted in significant inhibition of weight gain and improvement of glucose tolerance with reduced insulin secretion and beta-cell mass. These findings suggest that long-term GLP-1 treatment results in insulin sensitization of peripheral organs, rather than enhancement of beta-cell proliferation and function, particularly when animals are fed high-fat diet. Thus, the effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation largely depend on treatment dose, duration of treatment and meal contents. While GLP-1 enhances proliferation of beta-cells in some diabetic mice models, our results suggest that GLP-1 stimulates beta-cell growth only when expansion of beta-cell mass is required to meet metabolic demands.

Anodal tDCS over the Primary Motor Cortex Facilitates Long-Term Memory Formation Reflecting Use-Dependent Plasticity.

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Orjon Rroji

Full Text Available Previous research suggests that anodal transcranial direct current stimulation (tDCS over the primary motor cortex (M1 modulates NMDA receptor dependent processes that mediate synaptic plasticity. Here we test this proposal by applying anodal versus sham tDCS while subjects practiced to flex the thumb as fast as possible (ballistic movements. Repetitive practice of this task has been shown to result in performance improvements that reflect use-dependent plasticity resulting from NMDA receptor mediated, long-term potentiation (LTP-like processes. Using a double-blind within-subject cross-over design, subjects (n=14 participated either in an anodal or a sham tDCS session which were at least 3 months apart. Sham or anodal tDCS (1 mA was applied for 20 min during motor practice and retention was tested 30 min, 24 hours and one week later. All subjects improved performance during each of the two sessions (p < 0.001 and learning gains were similar. Our main result is that long term retention performance (i.e. 1 week after practice was significantly better when practice was performed with anodal tDCS than with sham tDCS (p < 0.001. This effect was large (Cohen's d=1.01 and all but one subject followed the group trend. Our data strongly suggest that anodal tDCS facilitates long-term memory formation reflecting use-dependent plasticity. Our results support the notion that anodal tDCS facilitates synaptic plasticity mediated by an LTP-like mechanism, which is in accordance with previous research.

Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease.

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Duffy, S J; Keaney , J F; Holbrook, M; Gokce, N; Swerdloff, P L; Frei, B; Vita, J A

2001-07-10

Epidemiological studies suggest that tea consumption decreases cardiovascular risk, but the mechanisms of benefit remain undefined. Endothelial dysfunction has been associated with coronary artery disease and increased oxidative stress. Some antioxidants have been shown to reverse endothelial dysfunction, and tea contains antioxidant flavonoids. Methods and Results-- To test the hypothesis that tea consumption will reverse endothelial dysfunction, we randomized 66 patients with proven coronary artery disease to consume black tea and water in a crossover design. Short-term effects were examined 2 hours after consumption of 450 mL tea or water. Long-term effects were examined after consumption of 900 mL tea or water daily for 4 weeks. Vasomotor function of the brachial artery was examined at baseline and after each intervention with vascular ultrasound. Fifty patients completed the protocol and had technically suitable ultrasound measurements. Both short- and long-term tea consumption improved endothelium- dependent flow-mediated dilation of the brachial artery, whereas consumption of water had no effect (Peffect on endothelium-independent nitroglycerin-induced dilation. An equivalent oral dose of caffeine (200 mg) had no short-term effect on flow-mediated dilation. Plasma flavonoids increased after short- and long-term tea consumption. Short- and long-term black tea consumption reverses endothelial vasomotor dysfunction in patients with coronary artery disease. This finding may partly explain the association between tea intake and decreased cardiovascular disease events.

Long-term Developmental Effects of Lactational Exposure to Lead Acetate on Ovary in Offspring Wistar Rats

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Mehran Dorostghoal

2011-01-01

Full Text Available Background: During the last decades, environmental contamination by lead generated from humanactivities has become an evident concern. The present study assessed the long-term effects ofneonatal exposure to different doses of lead acetate on the ovaries of offspring rats.Materials and Methods: Pregnant female Wistar rats were randomly divided into a control andthree experimental groups. The experimental groups received 20, 100 and 300 mg/L/day leadacetate via drinking water during lactation. Ovaries of the offspring were removed at 30, 60, 90 and120 days of age, their weights recorded and fixed in Bouin’s solution. Following tissue processing,5 μm serial sections were stained with hematoxylin-eosin, and then, the numbers and diameters ofovarian follicles and corpora lutea were estimated.Results: Ovary weights decreased significantly (p<0.05 in the 300 mg/L/day dose groups at 30,60 and 90 days postnatal development. Significant dose-related decreases were seen in the numbersof primary, secondary and antral follicles in 100 (p<0.05 and 300 mg/L/day doses groups at 30and 60 days of age (p<0.01. There was significant decrease in mean number of corpora lutea inthe 100 (p<0.05 and 300 (p<0.01 mg/L/day dose groups at 60 days of age. It seems that neonatallead treatment has transient effects on follicular development in the ovary of offspring and ovarianparameters gradually improve until 90 days of age.Conclusion: The present study showed that maternal lead acetate exposure affects prepubertalovarian follicle development in a dose dependent manner, but ovarian parameters gradually improveduring the postpubertal period.

High-dose benzodiazepine dependence: a qualitative study of patients' perception on cessation and withdrawal.

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Liebrenz, Michael; Gehring, Marie-Therese; Buadze, Anna; Caflisch, Carlo

2015-05-13

Benzodiazepine withdrawal syndrome has been reported following attempts to withdraw even from low or therapeutic doses and has been compared to barbiturate and alcohol withdrawal. This experience is known to deter patients from future cessation attempts. Research on other psychotropic substances shows that the reasons and motivations for withdrawal attempts - as well as the experiences surrounding those attempts - at least partially predict future efforts at discontinuation as well as relapse. We therefore aimed to qualitatively explore what motivates patients to discontinue this medication as well as to examine their experiences surrounding previous and current withdrawal attempts and treatment interventions in order to positively influence future help-seeking behavior and compliance. To understand these patients better, we conducted a series of 41 unstructured, narrative, in-depth interviews among adult Swiss patients with a long-term dependent use of benzodiazepines in doses equivalent to more than 40 mg diazepam per day and/or otherwise problematic use (mixing benzodiazepines, escalating dosage, recreational use or illegal purchase). Mayring's qualitative content analysis was used to evaluate findings. These high-dose benzodiazepine-dependent patients decision to change consumption patterns were affected by health concerns, the feeling of being addicted and social factors. Discontinuation attempts were frequent and not very successful with fast relapse. Withdrawal was perceived to be a difficult, complicated, and highly unpredictable process. The first attempt at withdrawal occurred at home and typically felt better than at the clinic. Inpatient treatment was believed to be more effective with long term treatment (approaches) than short term. Patients preferred gradual reduction of usage to abrupt cessation (and had experienced both). While no clear preferences for withdrawal were found for benzodiazepines with specific pharmacokinetic properties, participants

Long-Term Effectiveness and Safety of Dexmethylphenidate Extended-Release Capsules in Adult ADHD

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Adler, Lenard A.; Spencer, Thomas; McGough, James J.; Jiang, Hai; Muniz, Rafael

2009-01-01

Objective: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. Method: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness…

Long-term BPA infusions. Evaluation in the rat brain tumor and rat spinal cord models

International Nuclear Information System (INIS)

Coderre, J.A.; Micca, P.L.; Nawrocky, M.M.; Joel, D.D.; Morris, G.M.

2000-01-01

In the BPA-based dose escalation clinical trial, the observations of tumor recurrence in areas of extremely high calculated tumor doses suggest that the BPA distribution is non-uniform. Longer (6-hour) i.v. infusions of BPA are evaluated in the rat brain tumor and spinal cord models to address the questions of whether long-term infusions are more effective against the tumor and whether long-term infusions are detrimental in the central nervous system. In the rat spinal cord, the 50% effective doses (ED 50 ) for myeloparesis were not significantly different after a single i.p. injection of BPA-fructose or a 6 hour i.v. infusion. In the rat 9L gliosarcoma brain tumor model, BNCT following 2-hr or 6-hr infusions of BPA-F produced similar levels of long term survival. (author)

The effect of glucagon infusion on kidney function in short-term insulin-dependent juvenile diabetics

DEFF Research Database (Denmark)

Parving, H H; Christiansen, J S; Noer, I

1980-01-01

Kidney function was studied in nine, metabolically well controlled, short-term insulin-dependent male diabetics before and during glucagon infusion of 4 to 5 and 8 to 10 ng/kg/min. Glomerular filtration rate, effective renal plasma flow (steady-state infusion technique, with urinary collections......, using 125I-iothalamate and 131I-iodohippurate), and urinary albumin and beta 2-microglobulin excretion rates were measured. The mean plasma glucagon concentration increased during infusion from 254 +/- 19 pg/ml to 440 +/- 31 pg/ml (low dose) and 730 +/- 52 pg/ml (high dose). Glomerular filtration rate...... increased in all subjects from 133 +/- 5 before the glucagon infusion to 141 +/- 4 with the low dose, and 148 +/- 7 ml/min/1.73 m2 with the high dose (p

Effect of source term composition on offsite doses

International Nuclear Information System (INIS)

Karahalios, P.; Gardner, R.

1985-01-01

The development of new realistic accident source terms has identified the need to establish a basis for comparing the impact of such source terms. This paper attempts to develop a generalized basis of comparison by investigating contributions to offsite acute whole body doses from each group of radionuclides being released to the atmosphere, using CRAC2. The paper also investigates the effect of important parameters such as regional meteorology, sheltering, and duration of release. Finally, the paper focuses on significant changes in the relative importance of individual radionuclide groups in PWR2, SST1, and a revision of the Stone and Webster proposed interim source term

Normal tissue complication probabilities: dependence on choice of biological model and dose-volume histogram reduction scheme

International Nuclear Information System (INIS)

Moiseenko, Vitali; Battista, Jerry; Van Dyk, Jake

2000-01-01

Purpose: To evaluate the impact of dose-volume histogram (DVH) reduction schemes and models of normal tissue complication probability (NTCP) on ranking of radiation treatment plans. Methods and Materials: Data for liver complications in humans and for spinal cord in rats were used to derive input parameters of four different NTCP models. DVH reduction was performed using two schemes: 'effective volume' and 'preferred Lyman'. DVHs for competing treatment plans were derived from a sample DVH by varying dose uniformity in a high dose region so that the obtained cumulative DVHs intersected. Treatment plans were ranked according to the calculated NTCP values. Results: Whenever the preferred Lyman scheme was used to reduce the DVH, competing plans were indistinguishable as long as the mean dose was constant. The effective volume DVH reduction scheme did allow us to distinguish between these competing treatment plans. However, plan ranking depended on the radiobiological model used and its input parameters. Conclusions: Dose escalation will be a significant part of radiation treatment planning using new technologies, such as 3-D conformal radiotherapy and tomotherapy. Such dose escalation will depend on how the dose distributions in organs at risk are interpreted in terms of expected complication probabilities. The present study indicates considerable variability in predicted NTCP values because of the methods used for DVH reduction and radiobiological models and their input parameters. Animal studies and collection of standardized clinical data are needed to ascertain the effects of non-uniform dose distributions and to test the validity of the models currently in use

High-dose zolpidem dependence - Psychostimulant effects? A case report and literature review

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Abhijna Chandan Chattopadhyay

2016-01-01

Full Text Available Zolpidem, an imidazoline nonbenzodiazepine sedative drug, is used widely. Initial reports showed minimal abuse potential. However, multiple reports have appeared of dose escalation and abuse. Subjective effects of high-dose zolpidem are not known. In light of accumulating evidence of abuse potential, we hereby report a case of high-dose dependence and a review of relevant literature. A 33-year-old male presented with 5 years of daily use of 600–1700 mg of zolpidem tartrate. He reported subjective effects of euphoria, intense craving, and inability to stop use. Loss of receptor specificity, pharmacokinetic factors, and different receptor distributions can explain paradoxical stimulatory effects of high-dose zolpidem. Further studies are required to characterize subjective effects of high-dose zolpidem.

GABAergic activities control spike timing- and frequency-dependent long-term depression at hippocampal excitatory synapses

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Makoto Nishiyama

2010-06-01

Full Text Available GABAergic interneuronal network activities in the hippocampus control a variety of neural functions, including learning and memory, by regulating θ and γ oscillations. How these GABAergic activities at pre- and post-synaptic sites of hippocampal CA1 pyramidal cells differentially contribute to synaptic function and plasticity during their repetitive pre- and post-synaptic spiking at θ and γ oscillations is largely unknown. We show here that activities mediated by postsynaptic GABAARs and presynaptic GABABRs determine, respectively, the spike timing- and frequency-dependence of activity-induced synaptic modifications at Schaffer collateral-CA1 excitatory synapses. We demonstrate that both feedforward and feedback GABAAR-mediated inhibition in the postsynaptic cell controls the spike timing-dependent long-term depression of excitatory inputs (“e-LTD” at the θ frequency. We also show that feedback postsynaptic inhibition specifically causes e-LTD of inputs that induce small postsynaptic currents (<70 pA with LTP timing, thus enforcing the requirement of cooperativity for induction of long-term potentiation at excitatory inputs (“e-LTP”. Furthermore, under spike-timing protocols that induce e-LTP and e-LTD at excitatory synapses, we observed parallel induction of LTP and LTD at inhibitory inputs (“i-LTP” and “i-LTD” to the same postsynaptic cells. Finally, we show that presynaptic GABABR-mediated inhibition plays a major role in the induction of frequency-dependent e-LTD at α and β frequencies. These observations demonstrate the critical influence of GABAergic interneuronal network activities in regulating the spike timing and frequency dependences of long-term synaptic modifications in the hippocampus.

Long-term effects of interference on short-term memory performance in the rat.

Science.gov (United States)

Missaire, Mégane; Fraize, Nicolas; Joseph, Mickaël Antoine; Hamieh, Al Mahdy; Parmentier, Régis; Marighetto, Aline; Salin, Paul Antoine; Malleret, Gaël

2017-01-01

A distinction has always been made between long-term and short-term memory (also now called working memory, WM). The obvious difference between these two kinds of memory concerns the duration of information storage: information is supposedly transiently stored in WM while it is considered durably consolidated into long-term memory. It is well acknowledged that the content of WM is erased and reset after a short time, to prevent irrelevant information from proactively interfering with newly stored information. In the present study, we used typical WM radial maze tasks to question the brief lifespan of spatial WM content in rodents. Groups of rats were submitted to one of two different WM tasks in a radial maze: a WM task involving the repetitive presentation of a same pair of arms expected to induce a high level of proactive interference (PI) (HIWM task), or a task using a different pair in each trial expected to induce a low level of PI (LIWM task). Performance was effectively lower in the HIWM group than in LIWM in the final trial of each training session, indicative of a "within-session/short-term" PI effect. However, we also observed a different "between-session/long-term" PI effect between the two groups: while performance of LIWM trained rats remained stable over days, the performance of HIWM rats dropped after 10 days of training, and this impairment was visible from the very first trial of the day, hence not attributable to within-session PI. We also showed that a 24 hour-gap across training sessions known to allow consolidation processes to unfold, was a necessary and sufficient condition for the long-term PI effect to occur. These findings suggest that in the HIWM task, WM content was not entirely reset between training sessions and that, in specific conditions, WM content can outlast its purpose by being stored more permanently, generating a long-term deleterious effect of PI. The alternative explanation is that WM content could be transferred and stored

Long-term effects of interference on short-term memory performance in the rat.

Directory of Open Access Journals (Sweden)

Mégane Missaire

Full Text Available A distinction has always been made between long-term and short-term memory (also now called working memory, WM. The obvious difference between these two kinds of memory concerns the duration of information storage: information is supposedly transiently stored in WM while it is considered durably consolidated into long-term memory. It is well acknowledged that the content of WM is erased and reset after a short time, to prevent irrelevant information from proactively interfering with newly stored information. In the present study, we used typical WM radial maze tasks to question the brief lifespan of spatial WM content in rodents. Groups of rats were submitted to one of two different WM tasks in a radial maze: a WM task involving the repetitive presentation of a same pair of arms expected to induce a high level of proactive interference (PI (HIWM task, or a task using a different pair in each trial expected to induce a low level of PI (LIWM task. Performance was effectively lower in the HIWM group than in LIWM in the final trial of each training session, indicative of a "within-session/short-term" PI effect. However, we also observed a different "between-session/long-term" PI effect between the two groups: while performance of LIWM trained rats remained stable over days, the performance of HIWM rats dropped after 10 days of training, and this impairment was visible from the very first trial of the day, hence not attributable to within-session PI. We also showed that a 24 hour-gap across training sessions known to allow consolidation processes to unfold, was a necessary and sufficient condition for the long-term PI effect to occur. These findings suggest that in the HIWM task, WM content was not entirely reset between training sessions and that, in specific conditions, WM content can outlast its purpose by being stored more permanently, generating a long-term deleterious effect of PI. The alternative explanation is that WM content could be

Short-term and long-term effects of violent media on aggression in children and adults.

Science.gov (United States)

Bushman, Brad J; Huesmann, L Rowell

2006-04-01

To test whether the results of the accumulated studies on media violence and aggressive behavior are consistent with the theories that have evolved to explain the effects. We tested for the existence of both short-term and long-term effects for aggressive behavior. We also tested the theory-driven hypothesis that short-term effects should be greater for adults and long-term effects should be greater for children. Meta-analysis. Children younger than 18 years and adults. Violent media, including TV, movies, video games, music, and comic books. Measures of aggressive behavior, aggressive thoughts, angry feelings, physiological arousal (eg, heart rate, blood pressure), and helping behavior. Effect size estimates were combined using meta-analytic procedures. As expected, the short-term effects of violent media were greater for adults than for children whereas the long-term effects were greater for children than for adults. The results also showed that there were overall modest but significant effect sizes for exposure to media violence on aggressive behaviors, aggressive thoughts, angry feelings, arousal levels, and helping behavior. The results are consistent with the theory that short-term effects are mostly due to the priming of existing well-encoded scripts, schemas, or beliefs, which adults have had more time to encode. In contrast, long-term effects require the learning (encoding) of scripts, schemas, or beliefs. Children can encode new scripts, schemas, and beliefs via observational learning with less interference and effort than adults.

Effects of Chronic Vitamin D3 Hormone Administration on Anxiety-Like Behavior in Adult Female Rats after Long-Term Ovariectomy

Directory of Open Access Journals (Sweden)

Julia Fedotova

2017-01-01

Full Text Available The present preclinical study was created to determine the therapeutic effects of vitamin D hormone treatment as an adjunctive therapy alone or in a combination with low dose of 17β-estradiol (17β-E2 on anxiety-like behavior in female rats with long-term absence of estrogen. Accordingly, the aim of the current study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg subcutaneously, SC, once daily, for 14 days on the anxiety-like state after long-term ovariectomy in female rats. Twelve weeks postovariectomy, cholecalciferol was administered to ovariectomized (OVX rats and OVX rats treated with 17β-E2 (0.5 µg/rat SC, once daily, for 14 days. Anxiety-like behavior was assessed in the elevated plus maze (EPM and the light/dark test (LDT, and locomotor and grooming activities were tested in the open field test (OFT. Cholecalciferol at two doses of 1.0 and 2.5 mg/kg alone or in combination with 17β-E2 produced anxiolytic-like effects in OVX rats as evidenced in the EPM and the LDT, as well as increased grooming activity in the OFT. Our results indicate that cholecalciferol, at two doses of 1.0 and 2.5 mg/kg, has a profound anxiolytic-like effects in the experimental rat model of long-term estrogen deficiency.

Balloon dilatation of tuberculous bronchial stenosis: immediate and long term effect

International Nuclear Information System (INIS)

Lee, Sang Yoon; Kwak, Byung Kook; Kang, Ho Yeong; Kim, Tae Hoon; Kim, Soo Rhan; Park, Hyun Sun; Lee, Shin Hyung; Lee, Chang Joon

1997-01-01

To evaluate the long-term immediate effects of balloon dilatation of the tuberculous bronchial stenosis. Twenty-three women with tuberculous bronchial stenosis (19, left main bronchus ; 4, right main bronchus) underwent balloon dilatation (13 bronchoscopically guided ; 10 fluoroscopically guided). Immediate (n=23) and long-term follow-up (mean, 17.2 months; range, 1month-6years 3months ; n=20) assessments focused on changes in the results of the pulmonary function test (PFT). An increase in FVC or FEVI of more than 10% after the procedure was considered effective. In all patients, any complications were evaluated. Balloon dilatation was effective at immediate follow-up in 69.5% of patients(16/23) and in 75.0%(15/20) at long-term follow-up. Bronchoscopically and fluoroscopically-guided balloon dilatation proved effective in 61.5%(8/13) and 80.0% of patients(8/10) on immediate follow-up respectively, but in 90.0%(9/10) and 60.0%(6/10) on long term follow-up respectively. Balloon dilatation was effective in the active(n 10) and inactive(n = 13) stage of tuberculous bronchitis in 80.0%(8/10) and 61.5% of cases(8/13) on immediate follow-up respectively, but in 66.6%(6/9) and 81.8%(9/11) on long term follow-up study, respectively. On immediate follow-up, balloon dilatation of tubular bronchial stenosis was more effective in the active than in the inactive stage, but on long-term follow-up was less effective ; long-term improvement in the inactive stage was, however, well-maintained

Tritium contamination of hematopoietic stem cells alters long-term hematopoietic reconstitution

International Nuclear Information System (INIS)

Di Giacomo, F.; Barroca, V.; Laurent, D.; Lewandowski, D.; Saintigny, Y.; Romeo, P.H.; Granotier, Ch.; Boussin, F.D.

2011-01-01

Purpose: In vivo effects of tritium contamination are poorly documented. Here, we study the effects of tritiated Thymidine ([ 3 H] Thymidine) or tritiated water (HTO) contamination on the biological properties of hematopoietic stem cells (HSC). Materials and methods: Mouse HSC were contaminated with concentrations of [ 3 H] Thymidine ranging from 0.37-37.03 kBq/ml or of HTO ranging from 5-50 kBq/ml. The biological properties of contaminated HSC were studied in vitro after HTO contamination and in vitro and in vivo after [ 3 H] Thymidine contamination. Results: Proliferation, viability and double-strand breaks were dependent on [ 3 H] Thymidine or HTO concentrations used for contamination but in vitro myeloid differentiation of HSC was not affected by [ 3 H] Thymidine contamination. [ 3 H] Thymidine contaminated HSC showed a compromised long-term capacity of hematopoietic reconstitution and competition experiments showed an up to two-fold decreased capacity of contaminated HSC to reconstitute hematopoiesis. These defects were not due to impaired homing in bone marrow but to an initial decreased proliferation rate of HSC. Conclusion: These results indicate that contaminations of HSC with doses of tritium that do not result in cell death, induce short-term effects on proliferation and cell cycle and long-term effects on hematopoietic reconstitution capacity of contaminated HSC. (authors)

Factors impacting short and long-term kidney graft survival: modification by single intra-operative -high-dose induction with ATG-Fresenius.

Science.gov (United States)

Kaden, Jürgen; May, Gottfried; Völp, Andreas; Wesslau, Claus

2011-01-01

A majority of recipients benefited from the intra-operative single high-dose induction (HDI) with ATG-Fresenius (ATG-F) still leaving a group of recipients who did not profit from this kind of induction. Therefore the aim of this retrospective analysis was 1st to identify the risk factors impacting short and long-term graft survival, and 2nd to assess the efficacy of this type of induction in kidney graft recipients with or without these risk factors. A total of 606 recipients receiving two different immunosuppressive treatment regimens (1st: Triple drug therapy [TDT, n=196] consisting mainly of steroids, azathioprine and cyclosporine; 2nd: TDT + 9 mg/kg ATG-F intra-operatively [HDI, n=410]) were included in this analysis and grouped according to their kidney graft survival time (short GST: ≤1 yr, n=100 and long GST: >5 yrs, n=506). The main risk factors associated with a shortened graft survival were pre-transplant sensitization, re-transplantation, rejections (in particular vascular or mixed ones) and the necessity of a long-term anti-rejection therapy. Adding ATG-F single high dose induction to TDT was more efficient in prolonging kidney graft survival than TDT alone not only in recipients without any risk factors (p<0.005) but also in recipients with at least one risk factor (p<0.021). Only in 4.6% of recipients having two or more risk factors this effect could not be demonstrated. The intra-operative single high-dose induction with ATG-F significantly improves the kidney graft survival in recipients with or without risk factors and can therefore be recommended.

Effects of ethanolic extract and naphthoquinones obtained from the bulbs of Cipura paludosa on short-term and long-term memory: involvement of adenosine A₁ and A₂A receptors.

Science.gov (United States)

Lucena, Greice M R S; Matheus, Filipe C; Ferreira, Vania M; Tessele, Priscila B; Azevedo, Mariangela S; Cechinel-Filho, Valdir; Prediger, Rui D

2013-04-01

Previous studies from our group have indicated important biological properties of the ethanolic extract and isolated compounds from the bulbs of Cipura paludosa (Iridaceae), a native plant widely distributed in northern Brazil, including antioxidant, neuroprotective and anti-nociceptive activities. In the present study, the effects of the ethanolic extract and its two naphthoquinones (eleutherine and isoeleutherine) on the short- and long-term memory of adult rodents were assessed in social recognition and inhibitory avoidance tasks. Acute pre-training oral administration of the ethanolic extract improved the short-term social memory in rats as well as facilitated the step-down inhibitory avoidance short- and long-term memory in mice. Moreover, the co-administration of 'non-effective' doses of the extract of Cipura paludosa and the adenosine receptor antagonists caffeine (non-selective), DPCPX (adenosine A1 receptor antagonist) and ZM241385 (adenosine A2A receptor antagonist) improved the social recognition memory of rats. In the inhibitory avoidance task, the co-administration of sub-effective doses of the extract with caffeine or ZM241385, but not with DPCPX, improved the short- and long-term memory of mice. Finally, the acute oral administration of eleutherine and isoeleutherine facilitated the inhibitory avoidance short- and long-term memory in mice. These results demonstrate for the first time the cognitive-enhancing properties of the extract and isolated compounds from the bulbs of Cipura paludosa in rodents and suggest a possible involvement of adenosine A1 and A2A receptors in these effects. © 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.

Assessment of 226Ra age-dependent dose from water intake

International Nuclear Information System (INIS)

Porntepkasemsan, Boonsom; Srisuksawad, Kanitha

2008-01-01

The radioactivity in canal and ground waters collected in a 2-year long observation from the vicinity of the Rare Earth Research and Development Center (RRDC), Phathumthani Province, Thailand, was measured in order to determine the concentration of 226 Ra and to estimate the age-dependent effective dose to humans due to consumption. 226 Ra activities in both canal and ground waters were well below the WHO guidance level for drinking water quality of 1 Bq L -1 . The highest 226 Ra effective doses per year were found for infants and teens. However, the observed levels of calculated 226 Ra effective doses for all age groups in both canal and ground waters show satisfactory low values (less than 15 μSv yr -1 ). These values are acceptable in accordance with the WHO recommended reference dose level of 100 μSv yr -1 from water intake of 2 L day -1

Short- and long-term effects of real-time medication monitoring with short message service (SMS) reminders for missed doses on the refill adherence of people with Type 2 diabetes: evidence from a randomised controlled trial.

NARCIS (Netherlands)

Vervloet, M.; Dijk, L. van; Bakker, D.H. de; Souverein, P.C.; Santen-Reestman, J.; Vlijmen, B. van; Aarle, M.C.W. van; Hoek, L.S. van der; Bouvy, M.L.

2014-01-01

Aims: To investigate short- and long-term effects of real-time monitoring medication use combined with short message service (SMS) reminders for missed doses on refill adherence to oral anti-diabetic medication. Methods: A randomized controlled trial with two intervention groups and one control

Marijuana’s Dose-Dependent Effects in Daily Marijuana Smokers

OpenAIRE

Ramesh, Divya; Haney, Margaret; Cooper, Ziva D.

2013-01-01

Active marijuana produces significant subjective, psychomotor, and physiological effects relative to inactive marijuana, yet demonstrating that these effects are dose-dependent has proven difficult. This within-subject, double-blind study was designed to develop a smoking procedure to obtain a marijuana dose–response function. In four outpatient laboratory sessions, daily marijuana smokers (N = 17 males, 1 female) smoked six 5-s puffs from 3 marijuana cigarettes (2 puffs/cigarette). The numbe...

Involvement of melatonin metabolites in the long-term inhibitory effect of the hormone on rat spinal nociceptive transmission.

Science.gov (United States)

Mondaca, Mauricio; Hernández, Alejandro; Valladares, Luis; Sierralta, Walter; Noseda, Rodrigo; Soto-Moyano, Rubén

2004-02-01

There is evidence that melatonin and its metabolites could bind to nuclear sites in neurones, suggesting that this hormone is able to exert long-term functional effects in the central nervous system via genomic mechanisms. This study was designed to investigate (i) whether systemically administered melatonin can exert long-term effects on spinal cord windup activity, and (ii) whether blockade of melatonin degradation with eserine could prevent this effect. Rats receiving melatonin (10 mg/kg ip), the same dose of melatonin plus eserine (0.5 mg/kg ip), or saline were studied. Seven days after administration of the drugs or saline, spinal windup of rats was assessed in a C-fiber reflex response paradigm. Results show that rats receiving melatonin exhibited a reduction in spinal windup activity. This was not observed in the animals receiving melatonin plus eserine or saline, suggesting a role for melatonin metabolites in long-term changes of nociceptive transmission in the rat spinal cord.

Radiobiology in clinical radiation therapy: Long term risks - Carcinogenic, hereditary, and teratogenetic effects

International Nuclear Information System (INIS)

Brenner, David J.

1997-01-01

The long-term risks induced by radiation are of much concern to patients and clinicians alike. As an example, perceived radiation risks are frequently cited in a woman's decision to choose a radical mastectomy over lumpectomy + radiation. In consequence, the actual radiation risks are often considerably overstated, or unreasonably downplayed. In this lecture we will discuss just what is known about the long term risks following radiotherapy, both from the human experience and from the laboratory. We will discuss risks both to the patient and to radiotherapy personnel. A good deal is known about the carcinogenic effects of high and low doses of radiation, in large part thanks to the careful study of the survivors of the atomic bombing in Japan, as well as studies of individuals exposed to medical x rays. It is possible to make an estimate, which is probably good to within a factor of, perhaps, three to five, of the cancer risks faced by a patient of a particular age and sex who is going to undergo a particular radiotherapeutic regimen. It is also possible to make an estimate of the risks faced by radiotherapy and nursing staff exposed to low doses. Brachytherapy related risk estimates are likely to be somewhat more uncertain, due to the poorly known sparing effects of the low dose rates used; for the radiotherapy personnel in brachytherapy, because of the doses which can be received, the risks can be quite significant. A recent complication in external-beam radiotherapy is the advent of high-energy linacs, which can produce a significant fast neutron dose which, dose for dose, may be ten to fifty times more carcinogenic than gamma rays. Data relating to the risks of hereditary effects of radiation come almost entirely from laboratory experiments in animals. Studies involving several million mice form the basis of most of our current understanding of hereditary effects. The results of these studies indicate that radiation is a relatively inefficient mutagen. The

Genomic mutation study for long-term cells induced by carbon ions

International Nuclear Information System (INIS)

Wang, X.; Furusawa, Y.; Suzuki, M.; Hirayama, R.; Matsumoto, Y.; Qin, Y.

2007-01-01

samples at the HPRT locus was detected to measure 6-thioguanine-resistant colonies. Results: The survival fraction of the cells irradiated by carbon ions was lower than sparsely ionizing (low LET) radiation, and it was also lower in high dose rate (∼1.5Gy/min) than in low dose rate (∼0.008Gy/min) irradiated at the same dose. Furthermore, high dose (D10 dose) induced high mutation fraction. Low dose and low dose rate had the low mutation fractions and different dose rate induced different mutation fraction even at the same dose. Mutation fraction had lower value before 6 days, and the higher level between 12 to 24 days after irradiated, then value went down. Conclusion: The results suggest that high LET radiation may cause higher mutation induction dependent with irradiated dose. Different dose rate also may induce different mutation affection. The heavy ion radiation may cause the long-term genomic mutation and instability of cells. HPRT mutant detection system can be application evaluating the carcinogenic effects of space environmental radiation and heavy ion radiation therapy.

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.......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...

Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats.

Science.gov (United States)

Spiga, Saturnino; Talani, Giuseppe; Mulas, Giovanna; Licheri, Valentina; Fois, Giulia R; Muggironi, Giulia; Masala, Nicola; Cannizzaro, Carla; Biggio, Giovanni; Sanna, Enrico; Diana, Marco

2014-09-02

Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95-positive elements. Further analysis indicates that "long thin" but not "mushroom" spines are selectively affected. In addition, patch-clamp experiments from Nacc slices reveal that long-term depression (LTD) formation is hampered, with parallel changes in field potential recordings and reductions in NMDA-mediated synaptic currents. These changes are restricted to the withdrawal phase of ethanol dependence, suggesting their relevance in the genesis of signs and/or symptoms affecting ethanol withdrawal and thus the whole addictive cycle. Overall, these results highlight the key role of dynamic alterations in dendritic spines and their presynaptic afferents in the evolution of alcohol dependence. Furthermore, they suggest that the selective loss of long thin spines together with a reduced NMDA receptor function may affect learning. Disruption of this LTD could contribute to the rigid emotional and motivational state observed in alcohol dependence.

Misremembering what you see or hear: Dissociable effects of modality on short- and long-term false recognition.

Science.gov (United States)

Olszewska, Justyna M; Reuter-Lorenz, Patricia A; Munier, Emily; Bendler, Sara A

2015-09-01

False working memories readily emerge using a visual item-recognition variant of the converging associates task. Two experiments, manipulating study and test modality, extended prior working memory results by demonstrating a reliable false recognition effect (more false alarms to associatively related lures than to unrelated lures) within seconds of encoding in either the visual or auditory modality. However, false memories were nearly twice as frequent when study lists were seen than when they were heard, regardless of test modality, although study-test modality mismatch was generally disadvantageous (consistent with encoding specificity). A final experiment that varied study-test modality using a hybrid short- and long-term memory test (Flegal, Atkins & Reuter-Lorenz, 2010) replicated the auditory advantage in the short term but revealed a reversal in the long term: The false memory effect was greater in the auditory study-test condition than in the visual study-test condition. Thus, the same encoding conditions gave rise to an opposite modality advantage depending on whether recognition was tested under short-term or long-term memory conditions. Although demonstrating continuity in associative processing across delay, the results indicate that delay condition affects the availability of modality-dependent features of the memory trace and, thus, distinctiveness, leading to dissociable patterns of short- and long-term memory performance. (c) 2015 APA, all rights reserved).

Impaired fear memory specificity associated with deficient endocannabinoid-dependent long-term plasticity.

Science.gov (United States)

Lovelace, Jonathan W; Vieira, Philip A; Corches, Alex; Mackie, Ken; Korzus, Edward

2014-06-01

In addition to its central role in learning and memory, N-methyl D-aspartate receptor (NMDAR)-dependent signaling regulates central glutamatergic synapse maturation and has been implicated in schizophrenia. We have transiently induced NMDAR hypofunction in infant mice during postnatal days 7-11, followed by testing fear memory specificity and presynaptic plasticity in the prefrontal cortex (PFC) in adult mice. We show that transient NMDAR hypofunction during early brain development, coinciding with the maturation of cortical plasticity results in a loss of an endocannabinoid (eCB)-mediated form of long-term depression (eCB-LTD) at adult central glutamatergic synapses, while another form of presynaptic long-term depression mediated by the metabotropic glutamate receptor 2/3 (mGluR2/3-LTD) remains intact. Mice with this selective impairment of presynaptic plasticity also showed deficits in fear memory specificity. The observed deficit in cortical presynaptic plasticity may represent a neural maladaptation contributing to network instability and abnormal cognitive functioning.

Long-term consequences of small doses ionizing radiation effect on carbohydrate metabolism indices and their interrelation with incretory function on pancreas

International Nuclear Information System (INIS)

Akhmetov, E.A.

1998-01-01

Upon inspection of 100 liquidators of the Chernobyl accident consequences it was established that main pathogenic factors of the damaging effect of small dose ionizing radiation is its indirect action realized through the infringement of hormonal mechanisms of metabolism regulation. Carbohydrates metabolism disorders are considered from viewpoint of the hormonal status fluctuations in the liquidators of the Chernobyl accident consequences observed in the form of basal immunoreactive insulin level reduction and simultaneous increase of counter-insular hormones concentration in blood. Potential disorders in the glucose tolerance test have been observed in 32 % of the patients, decrease of immunoreactive insulin in 89 % and also increase of counter-insular hormones concentration in 52,8 %. Interrelation of revealed hormonal and metabolic changes with radiation factor in its long-term period was established. Marked changes are caused in the organism and stress effects of the radiation factor. By means of multifractal dispersion analysis it has been found that the contribution of the radiation factor in the propagation of the described changes constitutes 86,5 %. Sulphate-ion is shown to be able to taking incorporated long-living radionuclides from the organism along with the mitigation of their toxic effect. Application of the method of glucose tolerance test estimation by the generalized criterion allows to specify risk groups of the carbohydrates metabolism disorders propagation among the liquidators followed by the endocrinological observation, hormonal status control and application of preventive measures. (author)

The six year report: Acidification of surface water in Europe and North America. Dose/response relationships and long-term trends

Energy Technology Data Exchange (ETDEWEB)

Skjelkvaale, B L; Newell, A D; Raddum, G; Johannessen, M; Hovind, H; Tjomsland, T; Wathne, B M

1994-12-31

This report discusses The International Cooperative Programme on Assessment and Monitoring of Acidification of Rivers and Lakes, which is designed to (1) establish degree and extent of acidification of surface waters, (2) evaluate dose/response relationships and (3) define long-term trends and variations in aquatic chemistry and biota attributable to atmospheric pollution. Data from 200 sites in 14 countries of Europe and North America are available. Dose/response relationships show that the fauna is adapted to different water qualities in different regions, and that critical limits for the fauna must be calculated according to data for the specific region. Long-term trends of water chemistry show decreases in SO{sub 4}{sup 2-} and Ca{sup 2+} at many sites. Nitrate shows no consistent trends. 66 refs., 26 figs., 16 tabs.

Forecasting stock return volatility: A comparison between the roles of short-term and long-term leverage effects

Science.gov (United States)

Pan, Zhiyuan; Liu, Li

2018-02-01

In this paper, we extend the GARCH-MIDAS model proposed by Engle et al. (2013) to account for the leverage effect in short-term and long-term volatility components. Our in-sample evidence suggests that both short-term and long-term negative returns can cause higher future volatility than positive returns. Out-of-sample results show that the predictive ability of GARCH-MIDAS is significantly improved after taking the leverage effect into account. The leverage effect for short-term volatility component plays more important role than the leverage effect for long-term volatility component in affecting out-of-sample forecasting performance.

Long-term high-physiological-dose growth hormone reduces intra-abdominal fat in HIV-infected patients with a neutral effect on glucose metabolism

DEFF Research Database (Denmark)

Hansen, B R; Haugaard, S B; Jensen, Frank Krieger

2010-01-01

, glucose tolerance, and total plasma cholesterol and triglycerides did not significantly change during intervention. CONCLUSIONS: Daily 0.7 mg rhGH treatment for 40 weeks reduced abdominal visceral fat and trunk fat mass in HIV-infected patients. This treatment appeared to be safe with respect to glucose......OBJECTIVES: The aim of the study was to investigate the effect of long-term high-physiological-dose recombinant human growth hormone (rhGH) therapy on fat distribution and glucose metabolism in HIV-infected patients. METHODS: Forty-six HIV-infected Caucasian men on highly active antiretroviral...... between 1 and 3 pm for 40 weeks. Endpoints included changes in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), limb fat mass, percentage of limb fat, plasma lipids, insulin resistance and glucose tolerance. RESULTS: VAT and trunk fat mass decreased significantly in the GH group compared...

The effects of DHEA, 3beta-hydroxy-5alpha-androstane-6,17-dione, and 7-amino-DHEA analogues on short term and long term memory in the mouse.

Science.gov (United States)

Bazin, Marc-Antoine; El Kihel, Laïla; Boulouard, Michel; Bouët, Valentine; Rault, Sylvain

2009-11-01

Neurosteroids have been reported to modulate memory processes in rodents. Three analogues of dehydroepiandrosterone (DHEA), two of them previously described (7beta-aminoDHEA and 7beta-amino-17-ethylenedioxy-DHEA), and a new one (3beta-hydroxy-5alpha-androstane-6,17-dione) were synthesized, and their effects were evaluated on memory. This study examined their effects on long term and short term memory in male (6 weeks old) NMRI mice in comparison with the reference drug. Long term memory was assessed using the passive avoidance task and short term memory (spatial working memory) using the spontaneous alternation task in a Y maze. Moreover, the effects of DHEA and its analogues on spontaneous locomotion were measured. In all tests, DHEA and analogues were injected at three equimolar doses (0.300-1.350-6.075 microM/kg). DHEA and its three analogues administered immediately post-training at the highest doses (6.075 microM/kg, s.c.) improved retention in passive avoidance test. Without effect per se in the spatial working memory task, the four compounds failed to reverse scopolamine (1mg/kg, i.p.)-induced deficit in spontaneous alternation. These data suggested an action of DHEA and analogues in consolidation of long term memory particularly when emotional components are implied. Moreover, data indicated that pharmacological modulation of DHEA as performed in this study provides derivatives giving the same mnemonic profile than reference molecule.

Long-term effects of an intracavitary treatment with californium-252 on normal tissue. [Swine, /sup 226/Ra

Energy Technology Data Exchange (ETDEWEB)

Sullivan, M.F.; Beamer, J.L.; Mahony, T.D.; Cross, F.T.; Lund, J.E.; Endres, G.W.R.

1976-01-01

About one hundred fifty swine were exposed to either radium-226 or californium-252 sources in the uterine cervix to determine an RBE for both acute and long-term effects. That value for early changes in the tissues at risk in the treatment of cervical cancer was between 6.2 and 6.8. The incidence of complications increased with time after exposure, especially among animals treated with /sup 252/Cf. Analysis of rectal injury showed that ulceration occurred frequently within a year postexposure at doses between 1600 and 2400 rad calculated at 2 cm lateral to the source midline. Fat necrosis and smooth muscle atrophy, resulting in a local rectal stricture, were delayed changes observed in some animals. The lower ureter was the site for a greater frequency of complications than the GI tract. Ureteral stricture often occurred at doses of 1200 rad from /sup 252/Cf and 7000 rad from /sup 226/Ra. Observation of delayed effects in the uterine-cervix in animals held up to 4 years postexposure indicate that the RBE for /sup 252/Cf may be increased to a value as high as 18, while repair may have even decreased it to about 5.6 in the rectum. Fifty swine are still being observed for long-term effects after doses above 800 rad from /sup 252/Cf and 5000 rad from /sup 226/Ra.

Mood disorders and serotonin transporter density in ecstasy users - the influence of long-term abstention, dose, and gender

NARCIS (Netherlands)

de Win, Maartje M. L.; Reneman, Liesbeth; Reitsma, Johannes B.; den Heeten, Gerard J.; Booij, Jan; van den Brink, Wim

2004-01-01

Rationale. Neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") on the serotonin (5-HT) system have been described in animals and humans, but little is known about long-term effects of ecstasy use on mood. Objectives. To investigate short-term and long-term effects of ecstasy

[Stabilization and long-term effect of chromium contaminated soil].

Science.gov (United States)

Wang, Jing; Luo, Qi-Shi; Zhang, Chang-Bo; Tan, Liang; Li, Xu

2013-10-01

Short-term (3 d and 28 d) and long-term (1 a) stabilization effects of Cr contaminated soil were investigated through nature curing, using four amendments including ferrous sulfide, ferrous sulfate, zero-valent iron and sodium dithionite. The results indicated that ferrous sulfide and zero-valent iron were not helpful for the stabilization of Cr(VI) when directly used because of their poor solubility and immobility. Ferrous sulfate could effectively and rapidly decrease total leaching Cr and Cr(VI) content. The stabilization effect was further promoted by the generation of iron hydroxides after long-term curing. Sodium dithionite also had positive effect on soil stabilization. Appropriate addition ratio of the two chemicals could help maintain the soil pH in range of 6-8.

GluA2-dependent AMPA receptor endocytosis and the decay of early and late long-term potentiation: possible mechanisms for forgetting of short- and long-term memories.

Science.gov (United States)

Hardt, Oliver; Nader, Karim; Wang, Yu-Tian

2014-01-05

The molecular processes involved in establishing long-term potentiation (LTP) have been characterized well, but the decay of early and late LTP (E-LTP and L-LTP) is poorly understood. We review recent advances in describing the mechanisms involved in maintaining LTP and homeostatic plasticity. We discuss how these phenomena could relate to processes that might underpin the loss of synaptic potentiation over time, and how they might contribute to the forgetting of short-term and long-term memories. We propose that homeostatic downscaling mediates the loss of E-LTP, and that metaplastic parameters determine the decay rate of L-LTP, while both processes require the activity-dependent removal of postsynaptic GluA2-containing AMPA receptors.

Effects of long-term radiation exposure on chromosomal aberrations in radiological technologists

International Nuclear Information System (INIS)

Kumagai, Etsuko; Onomichi, Mitsukazu; Tanaka, Ryuji; Kumagai, Takashi; Sawada, Shozo.

1990-01-01

Chromosomal aberrations in the lymphocytes of radiation technologists (RT) were analyzed by the trypsin G-banding method to study the late effects of long-term exposure to low doses of radiation. Structural aberrations were identified in 384 (2.5%) of 15442 cells analyzed from 53 RT as compared to 177 (1.6%) of 11136 cells from 36 healthy controls. Stable aberrations were the most frequent in both groups and were either translocations or deletions. Unstable aberrations were mainly acentric fragments in both groups. The frequency of translocations and acentric fragments was significantly higher in the RT than in the controls and was highest in the RT over 50 years. The highest frequency observed in the >50 age group was attributed to the unknown for cumulative dose prior to introduction of film badges. Frequency of chromosomal aberrations correlated with the estimated dose from the film badges and years of experience of each RT based on the equation y=0.22+0.37D+4.35D 2 , where y is overall frequency of chromosomal aberrations and D is the estimated radiation dose in Sv. (author)

Long-Term Follow-up of Acoustic Schwannoma Radiosurgery With Marginal Tumor Doses of 12 to 13 Gy

International Nuclear Information System (INIS)

Chopra, Rahul; Kondziolka, Douglas; Niranjan, Ajay; Lunsford, L. Dade; Flickinger, John C.

2007-01-01

Purpose: To define long-term tumor control and clinical outcomes of radiosurgery with marginal tumor doses of 12 to 13 Gy for unilateral acoustic schwannoma. Methods and Materials: A total of 216 patients with previously untreated unilateral acoustic schwannoma underwent Gamma Knife radiosurgery between 1992 and 2000 with marginal tumor doses of 12 to 13 Gy (median, 13 Gy). Median follow-up was 5.7 years (maximum, 12 years; 41 patients with >8 years). Treatment volumes were 0.08-37.5 cm 3 (median, 1.3 cm 3 ). Results: The 10-year actuarial resection-free control rate was 98.3% ± 1.0%. Three patients required tumor resection: 2 for tumor growth and 1 partial resection for an enlarging adjacent subarachnoid cyst. Among 121 hearing patients with >3 years of follow-up, crude hearing preservation rates were 71% for keeping the same Gardner-Robertson hearing level, 74% for serviceable hearing, and 95% for any testable hearing. For 25 of these patients with intracanalicular tumors, the respective rates for preserving the same Gardner-Robertson level, serviceable hearing, and testable hearing were 80%, 88%, and 96%. Ten-year actuarial rates for preserving the same Gardner-Robertson hearing levels, serviceable hearing, any testable hearing, and unchanged facial and trigeminal nerve function were 44.0% ± 11.7%, 44.5% ± 10.5%, 85.3% ± 6.2%, 100%, and 94.9% ± 1.8%, respectively. Conclusions: Acoustic schwannoma radiosurgery with 12 to 13 Gy provides high rates of long-term tumor control and cranial nerve preservation after long-term follow-up

Long-Term Coffee Consumption Is Associated with Decreased Incidence of New-Onset Hypertension: A Dose-Response Meta-Analysis.

Science.gov (United States)

Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Pajak, Andrzej; Sciacca, Salvatore; Bes-Rastrollo, Maira; Galvano, Fabio; Martinez-Gonzalez, Miguel A

2017-08-17

To perform a dose-response meta-analysis of prospective cohort studies investigating the association between long-term coffee intake and risk of hypertension. An online systematic search of studies published up to November 2016 was performed. Linear and non-linear dose-response meta-analyses were conducted; potential evidence of heterogeneity, publication bias, and confounding effect of selected variables were investigated through sensitivity and meta-regression analyses. Seven cohorts including 205,349 individuals and 44,120 cases of hypertension were included. In the non-linear analysis, there was a 9% significant decreased risk of hypertension per seven cups of coffee a day, while, in the linear dose-response association, there was a 1% decreased risk of hypertension for each additional cup of coffee per day. Among subgroups, there were significant inverse associations for females, caffeinated coffee, and studies conducted in the US with longer follow-up. Analysis of potential confounders revealed that smoking-related variables weakened the strength of association between coffee consumption and risk of hypertension. Increased coffee consumption is associated with a modest decrease in risk of hypertension in prospective cohort studies. Smoking status is a potential effect modifier on the association between coffee consumption and risk of hypertension.

Dose- and type-dependent effects of long-chain fatty acids on adipogenesis and lipogenesis of bovine adipocytes.

Science.gov (United States)

Yanting, Chen; Yang, Q Y; Ma, G L; Du, M; Harrison, J H; Block, E

2018-02-01

Differentiation and lipid metabolism of adipocytes have a great influence on milk performance, health, and feed efficiency of dairy cows. The effects of dietary long-chain fatty acids (FA) on adipogenesis and lipogenesis of dairy cows are often confounded by other nutritional and physiological factors in vivo. Therefore, this study used an in vitro approach to study the effect of dose and type of long-chain FA on adipogenesis and lipogenesis of bovine adipocytes. Stromal vascular cells were isolated from adipose tissue of dairy cows and induced into mature adipocytes in the presence of various long-chain FA including myristic, palmitic, stearic, oleic, or linoleic acid. When concentrations of myristic, palmitic, and oleic acids in adipogenic mediums were 150 and 200 μM, the induced mature adipocytes had greater lipid content compared with other concentrations of FA. In addition, mature adipocytes induced at 100 μM stearic acid and 300 μM linoleic acid had the greatest content of lipid than at other concentrations. High concentrations of saturated FA were more toxic for cells than the same concentration of unsaturated FA during the induction. When commitment stage was solely treated with FA, the number of differentiated mature adipocytes was greater for oleic and linoleic acids than other FA. When the maturation stage was treated with FA, the number of mature adipocytes was not affected, but the lipid content in adipocytes was affected and ranked oleic > linoleic > myristic > stearic > palmitic. In summary, this study showed that adipogenesis and lipogenesis of bovine adipocytes were differentially affected by long-chain FA, with unsaturated FA more effective than saturated FA. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Long term effects of murine postnatal exposure to decabromodiphenyl ether (BDE-209) on learning and memory are dependent upon APOE polymorphism and age

DEFF Research Database (Denmark)

Reverte, Ingrid; Klein, Anders Bue; Domingo, José L

2014-01-01

exposure to BDE-209 induced long term effects in spatial learning, which were dependent upon age, sex and apoE genotype; these effects were more evident in apoE3 mice. BDNF levels were lower in the frontal cortex of apoE4 mice and higher in the hippocampus of exposed mice, independent of the genotype....... The results of the present study provide evidence of long-lasting effects in spatial learning and memory after early exposure to BDE-209. Developmental exposure to this neurotoxicant may contribute to cognitive decline and abnormal aging....... with varied vulnerability for the development of neurodegenerative diseases. On postnatal day 10, transgenic mice of both sexes carrying apoE2, apoE3 and apoE4 were orally exposed to 0, 10 or 30mg/kg of BDE-209. Spatial reference memory was assessed in a Morris Water Maze (MWM) task at 4 and 12months of age...

Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies

Science.gov (United States)

Finsterwald, Charles; Alberini, Cristina M.

2013-01-01

A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitaryadrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the effects of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the

Long-term Effects of Dexamethasone on Reproductive Parameters in Male Mice

Directory of Open Access Journals (Sweden)

jalogoden Gouyandeh

2015-02-01

Full Text Available Background & aim: The adverse effect of chemical drugs such as dexamethasone as anti-inflammatory -steroidal drugs on different body systems and infertility and reproductive efficiency is of concern. The purpose of this study was to evaluate the long-term effects of dexamethasone on the reproductive system in male rats. Methods: In the present experimental study, fifty matured male mice were divided into five groups including control, placebo and three treatment groups. Control group had no injections, placebo group only received normal saline and treatments groups received dexamethasone (0.1, 0.5 and 1 mg/kg which was injected in peritoneum every other day for a period of twenty days. Their Testosterone was measured by ELISA and testes were dissected for histological examination. The data were analyzed using SPSS 11.5 software. Results: Significant increases were shown in FSH level in all three groups treated with dexamethasone. LH in treatment group of 0.1 mg/kg decreased, but at dose of 1 mg/kg increased significantly.Testosterone levels in a dose of 1 mg/kg significantly increased compared with the control group (p<0.05. However, testis weight, the rate of testicular germ cells, primary spermatocytes, epididymal sperm and fertility significantly increased in all three groups (p<0.05. Conclusion: Dexamethasone had a negative effect on reproduction therefore, the use of this medication at different doses and time periods considers the possible complications beforehand. Keywords: .

A Cohort Study on Long-Term Adverse Effects of Parental Drinking: Background and Study Design

Directory of Open Access Journals (Sweden)

Ingunn Olea Lund

2015-01-01

Full Text Available Although many studies have addressed adverse outcomes in children of parents with alcohol abuse/dependence, less is known about the possible long-term effects of more normative patterns of parental alcohol consumption, including drinking at lower risk levels and heavy episodic or binge drinking. The extent of harm from parental drinking may therefore be underestimated. With this research proposal, we describe a project that aims to assess possible long-term adverse effects of parental drinking by combining survey and nationwide registry data. Advantages of a longitudinal general population cohort design include that it allows for detailed information on parental drinking through survey data and identification of possible negative long-term health and social outcomes from exposure to parental drinking 1–19 years after exposure through continuously updated nationwide registers. The rich information available from combining survey and registry data allows us to take into account important confounders, mediators, and moderators.

Clinical trials with rasagiline: evidence for short-term and long-term effects.

Science.gov (United States)

Siderowf, Andrew; Stern, Matthew

2006-05-23

Rasagiline (N-propargyl-1 (R)-aminoindan) is a selective, potent irreversible inhibitor of MAO-B that possesses neuroprotective and anti-apoptotic properties in a variety of in vitro and in vivo animal models relevant to Parkinson's disease (PD). Several randomized controlled clinical trials have demonstrated the safety and efficacy of rasagiline as monotherapy in PD and as adjunctive therapy for patients receiving levodopa. In addition, the 1-year randomized, delayed-start analysis of the TEMPO study suggests that rasagiline may slow the rate of progression of PD. The randomized delayed-start paradigm has potential to differentiate short-term symptomatic effects from long-term effects of anti-parkinsonian agents. In the future, long-term trials to examine the potential disease-modifying effects of rasagiline, which incorporate biological markers as well as clinical endpoints, may further elucidate the role of rasagiline in the treatment of both early and advanced PD.

Selenium homeostasis and induction of thioredoxin reductase during long term selenite supplementation in the rat

DEFF Research Database (Denmark)

Erkhembayar, Suvd; Mollbrink, Annelie; Eriksson, Malin

2011-01-01

-dependent increase in blood and liver selenium levels, with plateaus at 6 and 8weeks, respectively. These plateaus were reached at the same level of selenium regardless of dose, and no further accumulation was observed. A selenium-dependent increase in the activity of TrxR1 in parallel with the increase in liver...... selenium levels was also seen, and the induction of TrxR1 mRNA was seen only during the first three days of treatment, when the levels of selenium in the liver were increasing. Sodium selenite at 1 and 5μg/mL did not affect body weight or relative liver mass. We concluded that long-term treatment...... with selenite did not cause accumulation of selenium and that the activity of TrxR1 in the liver rose with the selenium levels. We therefore suggest that sodium selenite at doses up to 5μg/mL could be used for long-term tumour prevention....

Non-Competitive NMDA Receptor Antagonist Hemantane Reduces Ethanol Consumption in Long-Term Alcohol Experienced Rats.

Science.gov (United States)

Kolik, L G; Nadorova, A V; Seredenin, S B

2017-12-01

Activity of hemantane, an amino adamantane derivative, exhibiting the properties of lowaffinity non-competitive NMDA receptor antagonist, was evaluated in experimental in vivo models of alcoholism. Hemantane had no effects on the formation and manifestation of behavioral sensitization to ethanol in DBA/2 mice. Under conditions of free choice between 10% ethanol and water, hemantane (20 mg/kg/day for 14 days, intraperitoneally) significantly reduced the daily ethanol intake in random-bred male rats with formed alcohol motivation (>4 g/kg of ethanol). During modelling of withdrawal syndrome, hemantane administered intraperitoneally in doses of 5-20 mg/kg dose-dependently attenuated alcohol-deprivation effect after acute withdrawal with no effects on protracted abstinence. It was found that hemantane suppressed alcohol drinking behavior in long-term ethanol experienced rats and attenuated alcohol-seeking behavior after acute withdrawal.

Two separate dose-dependent effects of paroxetine

DEFF Research Database (Denmark)

Nielsen, Anette Green; Pedersen, Rasmus Steen; Nøhr-Jensen, Lene

2010-01-01

PURPOSE: To investigate paroxetine's putative dose-dependent impact on pupil reaction and inhibition of the O-demethylation of tramadol. METHODS: Twelve healthy CYP2D6 extensive metabolizers participated in this double-blinded randomized five-way placebo controlled cross-over study; they received...... concentrations of (+/-)-tramadol and (+/-)-O-desmethyltramadol (M1) were determined. RESULTS: With placebo, the median maximum pupil diameter was 6.43 mm (range 5.45-7.75 mm) before tramadol and 6.22 mm (4.35-7.65 mm) after 50 mg of tramadol (P = 0.4935). Paroxetine resulted in a statistically significant, dose......-dependent dilatation of the pupil with a geometric mean difference of 1.17 (95% CI 1.10-1.24) after ingestion of 50 mg paroxetine (P inhibition...

Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies.

Science.gov (United States)

Finsterwald, Charles; Alberini, Cristina M

2014-07-01

A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitary-adrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the formation of

Dose-Dependent Effects of Statins for Patients with Aneurysmal Subarachnoid Hemorrhage: Meta-Regression Analysis.

Science.gov (United States)

To, Minh-Son; Prakash, Shivesh; Poonnoose, Santosh I; Bihari, Shailesh

2018-05-01

The study uses meta-regression analysis to quantify the dose-dependent effects of statin pharmacotherapy on vasospasm, delayed ischemic neurologic deficits (DIND), and mortality in aneurysmal subarachnoid hemorrhage. Prospective, retrospective observational studies, and randomized controlled trials (RCTs) were retrieved by a systematic database search. Summary estimates were expressed as absolute risk (AR) for a given statin dose or control (placebo). Meta-regression using inverse variance weighting and robust variance estimation was performed to assess the effect of statin dose on transformed AR in a random effects model. Dose-dependence of predicted AR with 95% confidence interval (CI) was recovered by using Miller's Freeman-Tukey inverse. The database search and study selection criteria yielded 18 studies (2594 patients) for analysis. These included 12 RCTs, 4 retrospective observational studies, and 2 prospective observational studies. Twelve studies investigated simvastatin, whereas the remaining studies investigated atorvastatin, pravastatin, or pitavastatin, with simvastatin-equivalent doses ranging from 20 to 80 mg. Meta-regression revealed dose-dependent reductions in Freeman-Tukey-transformed AR of vasospasm (slope coefficient -0.00404, 95% CI -0.00720 to -0.00087; P = 0.0321), DIND (slope coefficient -0.00316, 95% CI -0.00586 to -0.00047; P = 0.0392), and mortality (slope coefficient -0.00345, 95% CI -0.00623 to -0.00067; P = 0.0352). The present meta-regression provides weak evidence for dose-dependent reductions in vasospasm, DIND and mortality associated with acute statin use after aneurysmal subarachnoid hemorrhage. However, the analysis was limited by substantial heterogeneity among individual studies. Greater dosing strategies are a potential consideration for future RCTs. Copyright © 2018 Elsevier Inc. All rights reserved.

Word Length Effects in Long-Term Memory

Science.gov (United States)

Tehan, Gerald; Tolan, Georgina Anne

2007-01-01

The word length effect has been a central feature of theorising about immediate memory. The notion that short-term memory traces rapidly decay unless refreshed by rehearsal is based primarily upon the finding that serial recall for short words is better than that for long words. The decay account of the word length effect has come under pressure…

Effects of long-term price increases for oil

International Nuclear Information System (INIS)

Voehringer, F.; Mueller, A.; Boehringer, C.

2007-03-01

This comprehensive report for the Swiss Federal Office of Energy (SFOE) takes a look at the effects of higher oil prices in the long-term. Scenarios examined include those with high oil prices of 80 to 140 dollars per barrel and those with drastic shortages resulting from peak extraction in the years 2010 and 2020. Long-term economic balances form the basis of the report, short-term influences and psychological effects are not addressed. The possible dangers for the earth's climate caused by the substitution of oil by coal-based products are discussed, as well as the sequestration of carbon dioxide. Ethanol and the associated conflicts of land use are examined and the decreasing cost-effectiveness of co-generation power generation is looked at. Alternatives such as atomic power, hydropower, solar energy, geothermal energy, biogas and wind power are discussed. The effect of the changing energy scene on economic growth and welfare aspects in Switzerland are examined. The authors conclude that high oil prices have considerable impacts on the economy and are not a substitute for an internationally co-ordinated climate policy

Age and Chronicity of Administration Dramatically Influenced the Impact of Low Dose Paraquat Exposure on Behavior and Hypothalamic-Pituitary-Adrenal Activity

Directory of Open Access Journals (Sweden)

Chris A. Rudyk

2017-07-01

Full Text Available Little is known of the age-dependent and long-term consequences of low exposure levels of the herbicide and dopaminergic toxicant, paraquat. Thus, we assessed the dose-dependent effects of paraquat using a typical short-term (3 week exposure procedure, followed by an assessment of the effects of chronic (16 weeks exposure to a very low dose (1/10th of what previously induced dopaminergic neuronal damage. Short term paraquat treatment dose-dependently induced deficits in locomotion, sucrose preference and Y-maze performance. Chronic low dose paraquat treatment had a very different pattern of effects that were also dependent upon the age of the animal: in direct contrast to the short-term effects, chronic low dose paraquat increased sucrose consumption and reduced forced swim test (FST immobility. Yet these effects were age-dependent, only emerging in mice older than 13 months. Likewise, Y-maze spontaneous alternations and home cage activity were dramatically altered as a function of age and paraquat chronicity. In both the short and long-term exposure studies, increased corticosterone and altered hippocampal glucocorticoid receptor (GR levels were induced by paraquat, but surprisingly these effects were blunted in the older mice. Thus, paraquat clearly acts as a systemic stressor in terms of corticoid signaling and behavioral outcomes, but that paradoxical effects may occur with: (a repeated exposure at; (b very low doses; and (c older age. Collectively, these data raise the possibility that repeated “hits” with low doses of paraquat in combination with aging processes might have promoted compensatory outcomes.

Long-term effects of pediatric extracorporeal shockwave lithotripsy on renal function

Science.gov (United States)

Akin, Yigit; Yucel, Selcuk

2014-01-01

Introduction Extracorporeal shock wave lithotripsy (ESWL) is a well-known and successful treatment modality. In addition, it can be used in premature infants. ESWL is used to treat kidney and ureter stones in children. However, although it is a preferred noninvasive treatment in that setting, there is debate about its long-term effects on growing kidneys in children. Objectives To investigate the long-term effects of pediatric ESWL on renal function in light of updated literature. Methods PubMed and Medline were searched for studies on ESWL in a pediatric population with keywords including efficacy, child, kidney calculi, ureter calculi, lithotripsy, injury, vascular trauma, and shock waves. The research was limited to the English literature during a period from 1980 to 2014. In total, 3,000 articles were evaluated, but only 151 papers were considered. Only the manuscripts directly related to the reviewed subjects were included in the current study. Results However, the acute effects of ESWL in kidney are well-described. Although there are limited studies on the long-term effects of ESWL in children, there is a widespread opinion that ESWL is not affecting renal functions in the long-term. Conclusion ESWL is a safe, effective, and noninvasive treatment option in children. Although ESWL can cause some acute effects in the kidney, there is no long-term effect on the growing kidneys of children. PMID:24892029

Bayesian estimation of dose rate effectiveness

International Nuclear Information System (INIS)

Arnish, J.J.; Groer, P.G.

2000-01-01

A Bayesian statistical method was used to quantify the effectiveness of high dose rate 137 Cs gamma radiation at inducing fatal mammary tumours and increasing the overall mortality rate in BALB/c female mice. The Bayesian approach considers both the temporal and dose dependence of radiation carcinogenesis and total mortality. This paper provides the first direct estimation of dose rate effectiveness using Bayesian statistics. This statistical approach provides a quantitative description of the uncertainty of the factor characterising the dose rate in terms of a probability density function. The results show that a fixed dose from 137 Cs gamma radiation delivered at a high dose rate is more effective at inducing fatal mammary tumours and increasing the overall mortality rate in BALB/c female mice than the same dose delivered at a low dose rate. (author)

Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate and behavior in attention-deficit hyperactivity disorder

NARCIS (Netherlands)

Schrantee, A. (Anouk); C. Bouziane (Cheima); E.E. Bron (Esther); S. Klein (Stefan); Bottelier, M.A.; Kooij, J.J.S.; S.A.R.B. Rombouts (Serge); L. Reneman (Liesbeth)

2017-01-01

textabstractStimulant prescription rates for attention deficit hyperactivity disorder (ADHD) are increasing, even though potential long-term effects on the developing brain have not been well-studied. A previous randomized clinical trial showed short-term age-dependent effects of stimulants on the

The effect of chronic corticosterone on fear learning and memory depends on dose and the testing protocol.

Science.gov (United States)

Marks, W N; Fenton, E Y; Guskjolen, A J; Kalynchuk, L E

2015-03-19

Chronic exposure to the stress hormone corticosterone (CORT) is known to alter plasticity within hippocampal and amygdalar circuits that mediate fear learning and memory. The purpose of this experiment was to clarify the effects of chronic CORT on Pavlovian fear conditioning, which is dependent on intact hippocampal and amygdalar activity. In particular, we assessed whether the effect of chronic CORT on fear learning and memory is influenced by two factors-the dose of CORT and the order in which rats are tested for freezing to context versus tone cues. Male Long-Evans rats received low-dose CORT (5mg/kg), high-dose CORT (40mg/kg), or vehicle injections once daily for 21days. On day 22, the rats were trained in a fear-conditioning paradigm. On days 23 and 24, the rats were tested for the retrieval of fear memories to context and tone cues in a counterbalanced way-half the rats received context testing on day 23 and then tone testing on day 24 and half the rats received tone testing on day 23 followed by context testing on day 24. Our results revealed dose-dependent effects of CORT on memory retrieval: Rats injected with high-dose CORT froze significantly more than control rats to both context and tone cues regardless of what testing day these cues were presented. However, rats injected with low-dose CORT froze significantly more than control rats to tone cues only. We also found an order effect in that the effects of CORT on freezing were greater on the second day of testing, regardless of whether that testing was to context or tones cues. This order effect may be due to a lack of extinction in the CORT rats. Overall, these results suggest a relationship between stress intensity and testing conditions that should be taken into account when assessing the effect of stress on fear memories. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Long-term effects of prenatal exposure to perfluoroalkyl substances on female reproduction

DEFF Research Database (Denmark)

Kristensen, Susanne Lund; Ramlau-Hansen, Cecilia; Ernst, Erik

2013-01-01

Does prenatal exposure to perfluoroalkyl substances (PFASs) have long-term effects on female reproductive function?.......Does prenatal exposure to perfluoroalkyl substances (PFASs) have long-term effects on female reproductive function?....

Short-term and long-term effects of GDP on traffic deaths in 18 OECD countries, 1960-2011.

Science.gov (United States)

Dadgar, Iman; Norström, Thor

2017-02-01

Research suggests that increases in gross domestic product (GDP) lead to increases in traffic deaths plausibly due to the increased road traffic induced by an expanding economy. However, there also seems to exist a long-term effect of economic growth that is manifested in improved traffic safety and reduced rates of traffic deaths. Previous studies focus on either the short-term, procyclical effect, or the long-term, protective effect. The aim of the present study is to estimate the short-term and long-term effects jointly in order to assess the net impact of GDP on traffic mortality. We extracted traffic death rates for the period 1960-2011 from the WHO Mortality Database for 18 OECD countries. Data on GDP/capita were obtained from the Maddison Project. We performed error correction modelling to estimate the short-term and long-term effects of GDP on the traffic death rates. The estimates from the error correction modelling for the entire study period suggested that a one-unit increase (US$1000) in GDP/capita yields an instantaneous short-term increase in the traffic death rate by 0.58 (pGDP leads to an immediate increase in traffic deaths. However, after the mid-1970s this short-term effect is more than outweighed by a markedly stronger protective long-term effect, whereas the reverse is true for the period before the mid-1970s. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Long-term follow-up study of compensated low-dose 131I therapy for Graves' disease

International Nuclear Information System (INIS)

Sridama, V.; McCormick, M.; Kaplan, E.L.; Fauchet, R.; DeGroot, L.J.

1984-01-01

We treated 187 patients who had Graves' disease with low-dose radioactive iodide ( 131 I), using a protocol that included a compensation for thyroid size. The incidence of early hypothyroidism (12 per cent) was acceptably low in the first year after 131 I treatment, but we found a cumulative high incidence (up to 76 per cent) at the end of the 11th year. In contrast, the incidence of permanent hypothyroidism was relatively stable in 166 surgically treated patients, increasing from 19 to 27 per cent at the end of 11 years. Among 122 medically treated patients, only 40 per cent entered remission, and hypothyroidism developed in 2 per cent during the same period of follow-up. The long-term incidence of hypothyroidism in our patients treated with low-dose 131 I therapy was much higher than that found in earlier studies using a comparable dose. Our study suggests that it will be difficult to modify therapy with 131 I alone to produce both early control of thyrotoxicosis and a low incidence of hypothyroidism

Constraints on the affinity term for modeling long-term glass dissolution rates

International Nuclear Information System (INIS)

Bourcier, W.L.; Carroll, S.A.; Phillips, B.L.

1993-11-01

Predictions of long-term glass dissolution rates are highly dependent on the form of the affinity term in the rate expression. Analysis of the quantitative effect of saturation state on glass dissolution rate for CSG glass (a simple analog of SRL-165 glass), shows that a simple (1-Q/K) affinity term does not match experimental results. Our data at 100 degree C show that the data is better fit by an affinity term having the form (1 - (Q/K) 1 /σ) where σ = 10

A retrieval account of the long-term modality effect.

Science.gov (United States)

Glenberg, A M

1984-01-01

When to-be-remembered (TBR) word pairs are separated by distractor activity, recall of the last few audibly presented pairs is greater than recall of the last few visually presented pairs. The effect is found even after a considerably long distractor-filled retention interval. Five experiments disconfirm echoic storage, short-term storage and long-term storage accounts of these effects, as well as demonstrating that the effect is not an artifact of differential use of a recency-first output strategy. The data are generally consistent with the proposition that retrieval is disrupted by modality-specific similarity between to-be-remembered items and distractor information.

Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate and behavior in attention-deficit hyperactivity disorder

NARCIS (Netherlands)

Schrantee, Anouk; Bouziane, C.; Bron, E. E.; Klein, S.; Bottelier, M. A.; Kooij, J. J. S.; Rombouts, S. A. R. B.; Reneman, L.

2017-01-01

Stimulant prescription rates for attention deficit hyperactivity disorder (ADHD) are increasing, even though potential long-term effects on the developing brain have not been well-studied. A previous randomized clinical trial showed short-term age-dependent effects of stimulants on the DA system. We

Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate and behavior in attention-deficit hyperactivity disorder.

NARCIS (Netherlands)

Schrantee, A.; Bouziane, C.; Bron, E.E.; Klein, S.; Bottelier, M.A.; Kooij, J.J.S.; Rombouts, S.A.R.B.; Reneman, L.

2017-01-01

Stimulant prescription rates for attention deficit hyperactivity disorder (ADHD) are increasing, even though potential long-term effects on the developing brain have not been well-studied. A previous randomized clinical trial showed short-term age-dependent effects of stimulants on the DA system. We

Long-Term Results After High-Dose Radiotherapy and Adjuvant Hormones in Prostate Cancer: How Curable Is High-Risk Disease?

Energy Technology Data Exchange (ETDEWEB)

Zapatero, Almudena, E-mail: azapatero.hlpr@salud.madrid.org [Department of Radiation Oncology, Hospital Universitario de la Princesa, Madrid (Spain); Garcia-Vicente, Feliciano [Department of Medical Physics, Hospital Universitario de la Princesa, Madrid (Spain); Martin de Vidales, Carmen; Cruz Conde, Alfonso; Ibanez, Yamile [Department of Radiation Oncology, Hospital Universitario de la Princesa, Madrid (Spain); Fernandez, Inmaculada; Rabadan, Mariano [Department of Urology, Hospital Universitario de la Princesa, Madrid (Spain)

2011-12-01

Purpose: To analyze long-term outcome and prognostic factors for high-risk prostate cancer defined by National Comprehensive Cancer Network criteria treated with high-dose radiotherapy and androgen deprivation in a single institution. Methods and Materials: A total of 306 patients treated between 1995 and 2007 in a radiation dose-escalation program fulfilled the National Comprehensive Cancer Network high-risk criteria. Median International Commission on Radiation Units and Measurements radiation dose was 78 Gy (range, 66.0-84.1 Gy). Long-term androgen deprivation (LTAD) was administered in 231 patients, short-term androgen deprivation (STAD) in 59 patients, and no hormones in 16 patients. The Phoenix (nadir plus 2 ng/mL) consensus definition was used for biochemical control. Multivariate analysis was performed to determine the independent prognostic impact of clinical and treatment factors. Median follow-up time was 64 months (range, 24-171 months). Results: The actuarial overall survival at 5 and 10 years was 95.7% and 89.8%, respectively, and the corresponding biochemical disease-free survival (bDFS) was 89.5% and 67.2%, respectively. Fourteen patients (4.6%) developed distant metastasis. Multivariate analysis showed that Gleason score >7 (p = 0.001), pretreatment prostate-specific antigen (PSA) level >20 ng/mL (p = 0.037), higher radiation dose (p = 0.005), and the use of adjuvant LTAD vs. STAD (p = 0.011) were independent prognostic factors affecting bDFS in high-risk disease. The 5-year bDFS for patients treated with LTAD plus radiotherapy dose >78 Gy was 97%. Conclusions: For high-risk patients the present series showed that the use of LTAD in conjunction with higher doses (>78 Gy) of radiotherapy was associated with improved biochemical tumor control. We observed that the presence of Gleason sum >7 and pretreatment PSA level >20 ng/mL in the same patient represents a 6.8 times higher risk of PSA failure. These men could be considered for clinical trials with

Long term exposure to low dose neurotoxic pesticides affects hatching, viability and cholinesterase activity of Artemia sp.

Science.gov (United States)

Gambardella, Chiara; Nichino, Daniela; Iacometti, Camillo; Ferrando, Sara; Falugi, Carla; Faimali, Marco

2018-03-01

The brine shrimp Artemia was used as a model organism to test toxicity of several neuroactive pesticides (chlorpyrifos (CLP), chlorpyrifos oxon (CLP ox), diazinon (DZN), carbaryl (CBR)) following exposure to far below than lethal doses. Cysts were exposed to the pesticides in order to test a scenario similar to actual coastal environment contamination, by analyzing different responses. Cysts were rehydrated in water containing the pesticides at concentrations ranging from 10 -11 to 10 -5  M, for 72, 96 and 192 h, respectively. For these exposure times, morpho-functional and biochemical parameters, such as hatching speed and viability were investigated in the larvae together with cholinesterase (ChE) activity quantification and histochemical localization. Finally, ChE inhibition was also compared with conventional selective ChE inhibitors. Results showed that CLP ox and CBR caused a significant dose-dependent decrease in hatching speed, followed by high percentages of larval death, while CLP and DZN were responsible for irregular hatching patterns. In addition, the pesticides mostly caused larval death some days post-hatching, whereas this effect was negligible for the specific ChE inhibitors, suggesting that part of pesticide toxicity may be due to molecules other than the primary target. ChE activity was observed in the protocerebrum lobes, linked to the development of pair eyes. Such activity was inhibited in larvae exposed to all pesticides. When compared to conventional selective inhibitors of ChE activities, this inhibition demonstrated that the selected pesticides mainly affect acetylcholinesterase and, to a lesser extent, pseudocholinesterases. In conclusion, the brine shrimp is a good model to test the environmental toxicity of long term exposure to cholinergic pesticides, since changes in hatching speed, viability and ChE activity were observed. Copyright © 2018 Elsevier B.V. All rights reserved.

Cooperative binding mitigates the high-dose hook effect.

Science.gov (United States)

Roy, Ranjita Dutta; Rosenmund, Christian; Stefan, Melanie I

2017-08-14

The high-dose hook effect (also called prozone effect) refers to the observation that if a multivalent protein acts as a linker between two parts of a protein complex, then increasing the amount of linker protein in the mixture does not always increase the amount of fully formed complex. On the contrary, at a high enough concentration range the amount of fully formed complex actually decreases. It has been observed that allosterically regulated proteins seem less susceptible to this effect. The aim of this study was two-fold: First, to investigate the mathematical basis of how allostery mitigates the prozone effect. And second, to explore the consequences of allostery and the high-dose hook effect using the example of calmodulin, a calcium-sensing protein that regulates the switch between long-term potentiation and long-term depression in neurons. We use a combinatorial model of a "perfect linker protein" (with infinite binding affinity) to mathematically describe the hook effect and its behaviour under allosteric conditions. We show that allosteric regulation does indeed mitigate the high-dose hook effect. We then turn to calmodulin as a real-life example of an allosteric protein. Using kinetic simulations, we show that calmodulin is indeed subject to a hook effect. We also show that this effect is stronger in the presence of the allosteric activator Ca 2+ /calmodulin-dependent kinase II (CaMKII), because it reduces the overall cooperativity of the calcium-calmodulin system. It follows that, surprisingly, there are conditions where increased amounts of allosteric activator actually decrease the activity of a protein. We show that cooperative binding can indeed act as a protective mechanism against the hook effect. This will have implications in vivo where the extent of cooperativity of a protein can be modulated, for instance, by allosteric activators or inhibitors. This can result in counterintuitive effects of decreased activity with increased concentrations of

Effects of treadmill exercise intensity on spatial working memory and long-term memory in rats.

Science.gov (United States)

Wang, Xiao-Qin; Wang, Gong-Wu

2016-03-15

Moderate exercise promotes learning and memory. Most studies mainly focused on memory exercise effects of in the ageing and patients. There is lack of quantitative research about effect of regular exercise intensity on different memory types in normal subjects. Present study investigated the effects of different intensities of treadmill exercise on working memory and long-term memory. Fifty female Wistar rats were trained by T-maze delayed spatial alternation (DSA) task with 3 delays (10s, 60s and 300s). Then they got a 30min treadmill exercise for 30days in 4 intensities (control, 0m/min; lower, 15m/min; middle, 20m/min, and higher, 30m/min). Then animals were tested in DSA, passive avoidance and Morris water maze tasks. 1. Exercise increased the neuronal density of hippocampal subregions (CA1, CA3 and dentate gyrus) vs. naïve/control. 2. In DSA task, all groups have similar baseline, lower intensity improved 10s delay accuracy vs. baseline/control; middle and higher intensities improved 300s delay accuracy vs. baseline/control. 3. In water maze learning, all groups successfully found the platform, but middle intensity improved platform field crossing times vs. control in test phase. Present results suggested that treadmill exercise can improve long-term spatial memory and working memory; lower intensity benefits to short-term delayed working memory, and middle or higher intensity benefits to long-term delayed working memory. There was an inverted U dose-effect relationship between exercise intensity and memory performance, but exercise -working memory effect was impacted by delay duration. Copyright © 2016 Elsevier Inc. All rights reserved.

Cost tradeoffs in consequence management at nuclear power plants: A risk based approach to setting optimal long-term interdiction limits for regulatory analyses

International Nuclear Information System (INIS)

Mubayi, V.

1995-05-01

The consequences of severe accidents at nuclear power plants can be limited by various protective actions, including emergency responses and long-term measures, to reduce exposures of affected populations. Each of these protective actions involve costs to society. The costs of the long-term protective actions depend on the criterion adopted for the allowable level of long-term exposure. This criterion, called the ''long term interdiction limit,'' is expressed in terms of the projected dose to an individual over a certain time period from the long-term exposure pathways. The two measures of offsite consequences, latent cancers and costs, are inversely related and the choice of an interdiction limit is, in effect, a trade-off between these two measures. By monetizing the health effects (through ascribing a monetary value to life lost), the costs of the two consequence measures vary with the interdiction limit, the health effect costs increasing as the limit is relaxed and the protective action costs decreasing. The minimum of the total cost curve can be used to calculate an optimal long term interdiction limit. The calculation of such an optimal limit is presented for each of five US nuclear power plants which were analyzed for severe accident risk in the NUREG-1150 program by the Nuclear Regulatory Commission

Long-term management of GERD in the elderly with pantoprazole

Directory of Open Access Journals (Sweden)

Carlo Calabrese

2007-04-01

Full Text Available Carlo Calabrese, Anna Fabbri, Giulio Di FeboDepartment of Internal Medicine and Gastroenterology, University of Bologna, ItalyAbstract: The prevalence of gastroesophageal reflux disease (GERD increases with age and elderly are more likely to develop severe disease. Older patients often complain of less severe or frequent heartburn than younger patients and they may present with atypical symptoms such as dysphagia, weight loss, or extraesophageal symptoms. Proton pump inhibitors (PPIs are central in the management of GERD and are unchallenged with regards to their efficacy. They are considered safe and more effective than histamine receptor antagonists for healing esophagitis and for preventing its recurrence using a long term maintenance treatment. PPI have minimal side effects and few slight drug interactions and are considered safe for long term treatment. Pantoprazole is significantly effective both for acute and long-term treatment with excellent control of relapse and symptoms. It is well tolerated even for long-term therapy and its tolerability is optimal. Pantoprazole shows to have minimal interactions with other drugs because of a lower affinity for cytocrome P450 than older PPIs. Although the majority of elderly has concomitant illnesses and receive other drugs, this does not adversely effect the efficacy of pantoprazole because of its pharmacokinetics, which are independent of patient age. Clinical practice suggests that a low dose maintenance of PPIs should be used in older patients with GERD.Keywords: GERD, long-term management, pantoprazole, safety, efficacy, tolerability

Long-term effects of radiotherapy on taste and salivary function in man

International Nuclear Information System (INIS)

Mossman, K.; Shatzman, A.; Chencharick, J.

1982-01-01

The long-term effects of radiotherapy on taste and salivary function were studied in 13 patients treated by radiation 1-7 years previously for tumors of the head and neck. Taste function was studied quantitatively using a standard forced choice, three-stimulus-drop technique for the determination of detection and recognition thresholds and a forced-scaling technique for the determination of taste intensity reponsiveness. Parotid salivary function was quantitatively evaluated by determination of flow rate and protein secretion rate. Nine of the 13 patients studied (69%) had measurable taste loss; every patient who had radiotherapy including the parotid glands had measurable salivary dysfunction. Our results demonstrate that curative courses of radiotherapy for tumors of the head and neck may result in long-term changes in taste and salivary function. From the present study, the maximum tolerance doses resulting in a 50% complication rate 5 years after treatment (TD 50/5) are estimated to be 40-65 Gy for xerostomia and 50-65 Gy for taste loss. Therefore, in a standard treatment regimen for tumors of the head and neck, with curative intent, gustatory and salivary gland tissues frequently sustain maximum tolerance injury

Effects of low doses of short-term gamma irradiation on growth and development through two generations of Pisum sativum

Energy Technology Data Exchange (ETDEWEB)

Zaka, R.; Misset, M.T. [UMR-CNRS 6553 Ecobio, Equipe Evolution des Populations et des Especes, Universite de Rennes 1, Campus de Beaulieu Bat. 14, Rennes Cedex F 35042 (France); Chenal, C. [Laboratoire de Radiobiologie, Universite de Rennes 1, Centre Regional de Lutte contre le Cancer, Rennes Cedex F 35062 (France)

2004-03-29

The effects of short-term gamma radiation on pea plants were investigated by exposing 5-day-old seedlings with doses ranging from 0 to 60 Gy, and studying plant growth and development over two generations after irradiation. Doses higher than 6 Gy significantly inhibited the G1 plant growth and productivity, and no seedling survived irradiation with 40 Gy and above. These effects were transmitted and were even more severe in the next generation, G2. Irradiated G1 ({>=}10 Gy) and G2 ({>=}0.4 Gy) plants were significantly smaller than controls. The mean number of pods produced per plant was reduced by at least 20% at all doses in both G1 and G2. In parallel, the mean numbers of ovules and normally developed seeds per pod were significantly reduced after 10 Gy in G1 and after 0.4 Gy in G2, leading to a significant drop in seed production. This effect was correlated with a linear decrease in male fertility linked to abnormal meiosis (tetrads with micronuclei) as a function of doses from 0 to 10 Gy, in G1 and G2 plants. These long-term changes in plant development demonstrate a genomic instability induced by irradiation. However, there were neither quantitative nor qualitative changes in storage proteins in G1 seeds at any of the irradiation doses tested from 0 to 10 Gy.

Long-term leaching behavior of vitrified high-level wastes

International Nuclear Information System (INIS)

Ishiguro, Katsuhiko; Sonobe, Hitoshi; Sasaki, Noriaki; Kashihara, Hidechiyo

1985-01-01

A long-term Soxhlet leaching test, long-term static leaching test, solubility evaluation test and actual-scale glass solid leaching test were carried out for simulated vitrified wastes. Under high flow-rate leachate conditions, the leaching of high-solubility substances such as B and Na increases almost linearly with time while that of Fe, Ni and rare earth metals strongly depends on their solubility. The overall leaching rate changes (tends to decrease) with time under static conditions. The elution or diffusion is the rate determining step in the earlier region of the leaching process while the solubilities of major components have greater effects in the latter region. The change of the dominant leaching mechanism is delayed more largely as the surface-area to leachate-volume (SA/V) ratio decreases. Actual-scale glass specimens showed almost the same leaching behaviors as small-scale ones. If cracks exist in glass solid, the leaching in them is slow causing little effects on the overall leaching rate. This may be due to the fact that solubility-dependent leaching is occuring in the cracks. The long-term static leaching observations were not satisfactorily explained by the MCC-3 type solubility test results. It is important to clarify the solubility-dependent leaching behaviors at large SA/V ratios. (Nogami, K.)

Some long-term effects of negative pions in mice exposed to partial body irradiation

International Nuclear Information System (INIS)

Coggle, J.E.

1977-01-01

The long-term effects of partial body exposure of one-day-old mice given either 60 Co γ rays or negative pions have been studied. Both radiations produced considerable life-shortening; for pions 6.8 +- 1.5% of life was lost per 100 rad and for γ rays the value was 5.7 +- 0.5% per 100 rad. The RBE of pions for ten weeks of life-shortening was about 1.3 compared with 60 Co γ rays, although at lower doses the RBE may be higher reaching about two for six weeks of life-shortening. The incidence rate of tumours at any particular age was greater in mice irradiated with pions at the peak and in those given higher doses of γ rays than in the controls. (author)

Driving ability in cancer patients receiving long-term morphine analgesia.

Science.gov (United States)

Vainio, A; Ollila, J; Matikainen, E; Rosenberg, P; Kalso, E

1995-09-09

When given in single doses to healthy volunteers, opioid analgesics impair reaction time, muscle coordination, attention, and short-term memory sufficiently to affect driving and other skilled activities. Despite the increasing use of oral morphine daily, little is known about the effect of long-term opioid therapy on psychomotor performance. To examine the effects of continuous morphine medication, psychological and neurological tests originally designed for professional motor vehicle drivers were conducted in two groups of cancer patients who were similar apart from experience of pain. 24 were on continuous morphine (mean 209 mg oral morphine daily) for cancer pain; and 25 were pain-free without regular analgesics. Though the results were a little worse in the patients taking morphine, there were no significant differences between the groups in intelligence, vigilance, concentration, fluency of motor reactions, or division of attention. Of the neural function tests, reaction times (auditory, visual, associative), thermal discrimination, and body sway with eyes open were similar in the two groups; only balancing ability with closed eyes was worse in the morphine group. These results indicate that, in cancer patients receiving long-term morphine treatment with stable doses, morphine has only a slight and selective effect on functions related to driving.

The long-term effects of switching from active intravenous bisphosphonate treatment to low-dose maintenance therapy in children with osteogenesis imperfecta.

Science.gov (United States)

Biggin, Andrew; Zheng, Linda; Briody, Julie N; Coorey, Craig P; Munns, Craig F

2015-01-01

Intravenous bisphosphonate therapy is the first-line treatment in moderate-to-severe osteogenesis imperfecta (OI), but there are varied treatment protocols with little data on long-term efficacy. This study evaluates the clinical outcomes when transitioning from active bisphosphonate treatment to maintenance therapy. A retrospective review was conducted on 17 patients before treatment, following active treatment (zoledronate 0.05 mg/kg 6-monthly or pamidronate 6-9 mg/kg/year) and after establishment on maintenance treatment for more than 2 years (zoledronate 0.025 mg/kg 6-monthly or pamidronate lean tissue mass increased during active treatment. These improvements were maintained during the period of maintenance treatment. Vertebral height improved in fractured thoracic vertebrae from pre-treatment to active therapy and improved further during maintenance treatment. Metacarpal cortical thickness and relative cortical area also increased over the treatment periods. Maintenance intravenous bisphosphonate therapy preserved the beneficial effects of active treatment at the doses stated above. Further studies are required to determine the optimal bisphosphonate treatment regimen in the management of children with OI. © 2015 S. Karger AG, Basel.

Interaction of Inhibitory and Facilitatory Effects of Conditioning Trials on Long-Term Memory Formation

Science.gov (United States)

Hosono, Shouhei; Matsumoto, Yukihisa; Mizunami, Makoto

2016-01-01

Animals learn through experience and consolidate the memories into long-time storage. Conditioning parameters to induce protein synthesis-dependent long-term memory (LTM) have been the subject of extensive studies in many animals. Here we found a case in which a conditioning trial inhibits or facilitates LTM formation depending on the intervals…

The Long-Term Effects of Youth Unemployment

Science.gov (United States)

Mroz, Thomas A.; Savage, Timothy H.

2006-01-01

Using NLSY data, we examine the long-term effects of youth unemployment on later labor market outcomes. Involuntary unemployment may yield suboptimal investments in human capital in the short run. A theoretical model of dynamic human capital investment predicts a rational "catch-up" response. Using semiparametric techniques to control for the…

Botulinum toxin type A in simple motor tics: short-term and long-term treatment-effects.

Science.gov (United States)

Rath, Judith J G; Tavy, Dénes L J; Wertenbroek, Agnes A A C M; van Woerkom, Theodoor C A M; de Bruijn, Sebastiaan F T M

2010-08-01

To determine the short-term and long-term treatment-effects of botulinum toxin type A in simple motor tics, we analyzed 15 consecutive patients (18 tics) with simple motor tics that were treated every 3 months with injections of BTX-A. Efficacy (rated on a 4-level scale) and duration of effect of the first 2 and last 2 (if treated 5 times or more) treatments were recorded, as well as latency of response, changes of premonitory urges (PMUs) and possible side effects. Total number of treatments for each tic varied from 2 to 50 (mean 11, median 6). In 16 of 18 tics (89%) short-term efficacy was reported successful (good or moderate). Long-term efficacy was reported in 12 tics of which 11 showed similar or even increased beneficial effects. Premonitory urge (PMU) was reported in 8 patients (53%). PMU, if present, lessened or disappeared after treatment with BTX-A. A permanent remission of the treated tic was seen in 3 patients with a maximum follow-up of 10 years. BTX-A appears a safe and effective treatment for simple motor tics and retains its efficacy after long-term treatment. BTX may also induce permanent remission of the treated tics and effects of BTX are not restricted to merely motor behaviour.

Effect of long-term calcitonin administration on steroid-induced osteoporosis after cardiac transplantation.

Science.gov (United States)

Kapetanakis, Emmanouil I; Antonopoulos, Athanassios S; Antoniou, Theofani A; Theodoraki, Kassiani A; Zarkalis, Dimitrios A; Sfirakis, Peter D; Chilidou, Despina A; Alivizatos, Peter A

2005-05-01

Early, rapid bone loss and fractures after cardiac transplantation are well-documented complications of steroid administration; therefore, we undertook this study on the effects of long-term calcitonin on steroid-induced osteoporosis. Twenty-three heart transplant recipients on maintenance immunosuppression with cyclosporine, mycophenolate mofetil and prednisone were retrospectively studied. All patients received long-term prophylactic treatment with elemental calcium and vitamin D. Twelve (52.2%) patients also received long-term intranasal salmon calcitonin, whereas 11 (47.8%) received none. Bone mineral density and vertebral fractures were assessed at yearly intervals. Statistical comparisons between each group's bone loss during the first year and in the early (1 to 3 years), intermediate (4 to 6 years) and late (7+ years) post-transplantation periods were done. Lumbar spine bone loss was significant during the early follow-up period in the group not receiving calcitonin (0.744 +/- 0.114 g/cm(2) vs 0.978 +/- 0.094 g/cm(2) [p = 0.002]). The calcitonin group showed bone mineral density (BMD) levels within normal average values throughout the study period. BMD increased in the no-calcitonin group during the intermediate (4 to 6 years) and late (7+ years) follow-up periods, with values approaching normal average and no significant difference between the 2 groups (0.988 +/- 0.184 g/cm(2) vs 0.982 +/- 0.088 g/cm(2) [p = 0.944] and 0.89 +/- 0.09 g/cm(2) vs 1.048 +/- 0.239 g/cm(2) [p = 0.474], respectively). Prophylactic treatment with intranasal salmon calcitonin prevents rapid bone loss associated with high-dose steroids early after cardiac transplantation. Long-term administration does not seem warranted in re-establishing BMD.

Long-term impact of postoperative radiotherapy in carcinoma of the vulva FIGO I/II

International Nuclear Information System (INIS)

Busch, Martin; Wagener, Birgit; Schaffer, Moshe; Duehmke, Eckhart

2000-01-01

Purpose: Between 1953 and 1978, postoperative radiotherapy was used as an adjuvant therapy for carcinoma of the vulva that had not been treated with radical vulvectomy. We evaluated long-term results and possible prognostic factors. Methods and Materials: Ninety-two patients were treated. Surgical procedures were simple vulvectomy, electrocoagulation, or local excision. Radiotherapy doses to the vulva ranged from 0 to 90 Gy. All patients received radiotherapy to the inguinal lymph nodes, ranging from 30 to 60 Gy. Thirty-year retrospective follow-up was done evaluating the records and statistical survival rates. Results: Five-year actuarial survival rates in T1 patients were 71% (77% cause-specific survival rate), for T2 patients 43% (48% cause-specific survival rate). The difference between T1 and T2 patients was significant (p < 0.05). Patients with tumors of the labia minora had a significantly higher survival rate than those with different sites affected. Doses of 45 Gy or more to the vulva were sufficient to increase the 5-year cause-specific survival rate from 55% to 88%. The results in three subgroups were analyzed, group 1 having received electrocoagulation, but no radiotherapy of the vulva; group 2, local excision and doses of 40 Gy to the vulva; group 3, local excision and doses of 60 Gy to the vulva. There was a significant effect on 10-year cause-specific survival rates: 48% in group 1, 11% in group 2, and 88% in group 3. In multivariate analysis, the significant independent factors were T classification, tumor sites and--with only marginal significance--radiation doses to the vulva. Conclusions: The prognosis in early vulva carcinoma after nonradical surgery primarily depends on T classification and the site of the primary tumor. With univariate analyses, the dose has a significant effect on survival. In multivariate analyses the dose is a marginal independent factor in the whole group of patients. After nonradical surgery of early vulva carcinoma, the

Sex-Dependent and Independent Effects of Long-Term Voluntary Wheel Running on Bdnf mRNA and Protein Expression

OpenAIRE

Venezia, Andrew C.; Guth, Lisa M.; Sapp, Ryan M.; Spangenburg, Espen E.; Roth, Stephen M.

2016-01-01

The beneficial effects of physical activity on brain health (synaptogenesis, neurogenesis, enhanced synaptic plasticity, improved learning and memory) appear to be mediated through changes in region-specific expression of neurotrophins, transcription factors, and postsynaptic receptors, though investigations of sex differences in response to long-term voluntary wheel running are limited.

CLIMATE CHANGE: LONG-TERM TRENDS AND SHORT-TERM OSCILLATIONS

Institute of Scientific and Technical Information of China (English)

GAO Xin-quan; ZHANG Xin; QIAN Wei-hong

2006-01-01

Identifying the Northern Hemisphere (NH) temperature reconstruction and instrumental data for the past 1000 years shows that climate change in the last millennium includes long-term trends and various oscillations. Two long-term trends and the quasi-70-year oscillation were detected in the global temperature series for the last 140 years and the NH millennium series. One important feature was emphasized that temperature decreases slowly but it increases rapidly based on the analysis of different series. Benefits can be obtained of climate change from understanding various long-term trends and oscillations. Millennial temperature proxies from the natural climate system and time series of nonlinear model system are used in understanding the natural climate change and recognizing potential benefits by using the method of wavelet transform analysis. The results from numerical modeling show that major oscillations contained in numerical solutions on the interdecadal timescale are consistent with that of natural proxies. It seems that these oscillations in the climate change are not directly linked with the solar radiation as an external forcing. This investigation may conclude that the climate variability at the interdecadal timescale strongly depends on the internal nonlinear effects in the climate system.

The effects of prolonged administration of norepinephrine reuptake inhibitors on long-term potentiation in dentate gyrus, and on tests of spatial and object recognition memory in rats.

Science.gov (United States)

Walling, Susan G; Milway, J Stephen; Ingram, Matthew; Lau, Catherine; Morrison, Gillian; Martin, Gerard M

2016-02-01

Phasic norepinephrine (NE) release events are involved in arousal, novelty detection and in plasticity processes underlying learning and memory in mammalian systems. Although the effects of phasic NE release events on plasticity and memory are prevalently documented, it is less understood what effects chronic NE reuptake inhibition and sustained increases in noradrenergic tone, might have on plasticity and cognitive processes in rodent models of learning and memory. This study investigates the effects of chronic NE reuptake inhibition on hippocampal plasticity and memory in rats. Rats were administered NE reuptake inhibitors (NRIs) desipramine (DMI; 0, 3, or 7.5mg/kg/day) or nortriptyline (NTP; 0, 10 or 20mg/kg/day) in drinking water. Long-term potentiation (LTP; 200 Hz) of the perforant path-dentate gyrus evoked potential was examined in urethane anesthetized rats after 30-32 days of DMI treatment. Short- (4-h) and long-term (24-h) spatial memory was tested in separate rats administered 0 or 7.5mg/kg/day DMI (25-30 days) using a two-trial spatial memory test. Additionally, the effects of chronically administered DMI and NTP were tested in rats using a two-trial, Object Recognition Test (ORT) at 2- and 24-h after 45 and 60 days of drug administration. Rats administered 3 or 7.5mg/kg/day DMI had attenuated LTP of the EPSP slope but not the population spike at the perforant path-dentate gyrus synapse. Short- and long-term memory for objects is differentially disrupted in rats after prolonged administration of DMI and NTP. Rats that were administered 7.5mg/kg/day DMI showed decreased memory for a two-trial spatial task when tested at 4-h. In the novel ORT, rats receiving 0 or 7.5mg/kg/day DMI showed a preference for the arm containing a Novel object when tested at both 2- and 24-h demonstrating both short- and long-term memory retention of the Familiar object. Rats that received either dose of NTP or 3mg/kg/day DMI showed impaired memory at 2-h, however this

Conversion of short-term to long-term memory in the novel object recognition paradigm.

Science.gov (United States)

Moore, Shannon J; Deshpande, Kaivalya; Stinnett, Gwen S; Seasholtz, Audrey F; Murphy, Geoffrey G

2013-10-01

It is well-known that stress can significantly impact learning; however, whether this effect facilitates or impairs the resultant memory depends on the characteristics of the stressor. Investigation of these dynamics can be confounded by the role of the stressor in motivating performance in a task. Positing a cohesive model of the effect of stress on learning and memory necessitates elucidating the consequences of stressful stimuli independently from task-specific functions. Therefore, the goal of this study was to examine the effect of manipulating a task-independent stressor (elevated light level) on short-term and long-term memory in the novel object recognition paradigm. Short-term memory was elicited in both low light and high light conditions, but long-term memory specifically required high light conditions during the acquisition phase (familiarization trial) and was independent of the light level during retrieval (test trial). Additionally, long-term memory appeared to be independent of stress-mediated glucocorticoid release, as both low and high light produced similar levels of plasma corticosterone, which further did not correlate with subsequent memory performance. Finally, both short-term and long-term memory showed no savings between repeated experiments suggesting that this novel object recognition paradigm may be useful for longitudinal studies, particularly when investigating treatments to stabilize or enhance weak memories in neurodegenerative diseases or during age-related cognitive decline. Copyright © 2013 Elsevier Inc. All rights reserved.

The Long-Term Effect of Childhood Poverty

OpenAIRE

Lesner, Rune Vammen

2016-01-01

This paper uses variation among siblings to identify the effect of childhood poverty on long-term outcomes such as income, earnings, job type, employment, and having children. Childhood poverty is found to have large negative effects on labour market outcome and small effects on non-labour market outcomes. The marginal effect of one additional year of childhood poverty from the age of 13 to 15 is found to decrease the disposable income of the individual by 6.4% around the age of 30. The effec...

Long-term effects of low-level radiation exposure, experimental studies

International Nuclear Information System (INIS)

Bond, V.P.

1978-05-01

Important considerations in the quantitative estimate of risk of carcinogenesis in the human being are the related factors of the shape of the dose-effect curve, the risk per rad at very low doses (about 10 rad or less) vs. higher doses, and the effect per rad of higher doses delivered at very low dose rates. Data on the human being, though extensive and adequate for quantitative risk estimation at high doses and dose rates, do not allow definitive conclusions on these factors. Data on eukaryotic cells are represented well and in detail by a modified quadratic relationship with a definite linear term, and indicate that both the simple linear and the pure quadratic relationships are rare or essentially nonexistent. A dose rate effect is ubiquitous, but the extent varies widely among different tumors and species. Extensive data on carcinogenesis in mammals are in general represented well by the linear-quadratic model, although simple linearity and the pure quadratic (or threshold) models cannot be excluded in a few tumor systems. Considerations and uncertainties in addition to curve shape and dose rate may tend to offset any credit that might be afforded by dose rate. Hence, while it is almost certain that dose rate does at least to some degree affect (reduce) the current risk estimated based on linearity, it also seems clear that, at least for some time, current carcinogenesis risk estimates based on linearity probably will continue to be used as an approximation of the degree of risk associated with radiation exposure at very low doses and dose rates

Medium- and long-term consequences of pollution on labor supply: evidence from Indonesia

Directory of Open Access Journals (Sweden)

Younoh Kim

2017-04-01

Full Text Available Abstract We use a natural experiment in Indonesia to study the medium- and long-term effects of air pollution on labor supply. We find that exposure to air pollution reduces hours worked and while the medium-term effects are larger in magnitude, some effects do persist in the long term. More interestingly, we are able to provide some insight regarding the underlying channels that contribute to the reduced labor supply. Own health seems to be the only responsible channel in the long term, while in the medium term, a different channel based on dependent caregiving is the most important. JEL Classification: J22, Q53

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,…

Short- and Long-Term Effects of Adolescent Alcohol Access: Evidence from Denmark

DEFF Research Database (Denmark)

Gupta, Nabanita Datta; Nilsson, Anton

We exploit changes in minimum legal alcohol purchasing ages in Denmark in order to estimate effects on short- and long-term health outcomes, as well as on human capital formation. Employing a difference-in-differences approach for immediate outcomes and a “regression kink design” for long......-term outcomes, we bring comprehensive evidence on the health and education effects of three reforms, which affected alcohol availability along different dimensions and margins – 1) establishing an off-premise alcohol purchase age of 15 (1998), 2) raising the off-premise alcohol purchase age to 16 (2004), and 3......) increasing the purchase age of beverages exceeding 16.5% in alcohol content from 16 to 18 (2011). Our findings show significant short-term effects of the first and third reforms in terms of reducing injuries and alcohol-related conditions, and some long-term effects of the first reform in terms of reducing...

Brief, pre-retrieval stress differentially influences long-term memory depending on sex and corticosteroid response.

Science.gov (United States)

Zoladz, Phillip R; Kalchik, Andrea E; Hoffman, Mackenzie M; Aufdenkampe, Rachael L; Burke, Hanna M; Woelke, Sarah A; Pisansky, Julia M; Talbot, Jeffery N

2014-03-01

Previous work has indicated that stress generally impairs memory retrieval. However, little research has addressed discrepancies that exist in this line of work and the factors that could explain why stress can exert differential effects on retrieval processes. Therefore, we examined the influence of brief, pre-retrieval stress that was administered immediately before testing on long-term memory in males and females. Participants learned a list of 42 words varying in emotional valence and arousal. Following the learning phase, participants were given an immediate free recall test. Twenty-four hours later, participants submerged their non-dominant hand in a bath of ice cold (Stress) or warm (No Stress) water for 3 min. Immediately following this manipulation, participants' memory for the word list was assessed via free recall and recognition tests. We observed no group differences on short-term memory. However, male participants who showed a robust cortisol response to the stress exhibited enhanced long-term recognition memory, while male participants who demonstrated a blunted cortisol response to the stress exhibited impaired long-term recall and recognition memory. These findings suggest that the effects of brief, pre-retrieval stress on long-term memory are sex-specific and mediated by corticosteroid mechanisms. Copyright © 2014 Elsevier Inc. All rights reserved.

Dose Dependent Survival Response in Chronic Myeloid Leukemia under Continuous and Pulsed Targeted Therapy

International Nuclear Information System (INIS)

Pizzolato, N.; Valenti, D.; Spagnolo, B.; Persano Adorno, D.

2010-01-01

A simulative study of cancer growth dynamics in patients affected by Chronic Myeloid Leukemia (CML), under the effect of a targeted dose dependent continuous or pulsed therapy, is presented. We have developed a model for the dynamics of CML in which the stochastic evolution of white blood cell populations are simulated by adopting a Monte Carlo approach. Several scenarios in the evolutionary dynamics of white blood cells, as a consequence of the efficacy of the different modelled therapies, pulsed or continuous, are described. The best results, in terms of a permanent disappearance of the leukemic phenotype, are achieved with a continuous therapy and higher dosage. However, our findings demonstrate that an intermittent therapy could represent a valid choice in patients with high risk of toxicity, when a long-term therapy is considered. A suitably tuned pulsed therapy can enhance the treatment efficacy and reduce the percentage of patients developing resistance. (authors)

Radiobiology in clinical radiation therapy - Part IV: Long term risks - Carcinogenic, hereditary, and teratogenetic effects

International Nuclear Information System (INIS)

Brenner, David J.

1996-01-01

The long-term risks induced by radiation are of much concern to patients and clinicians alike. As an example, perceived radiation risks are frequently cited in a woman's decision to choose a radical mastectomy over lumpectomy + radiation. In consequence, the actual radiation risks are often considerably overstated, or unreasonably downplayed. In this lecture we will discuss just what is known about the long term risks following radiotherapy, both from the human experience and from the laboratory. We will discuss risks both to the patient and to radiotherapy personnel. A good deal is known about the carcinogenic effects of high and low doses of radiation, in large part thanks to the careful study of the survivors of the atomic bombing in Japan, as well as studies of individuals exposed to medical x rays. It is possible to make an estimate, which is probably good to within a factor of, perhaps, three to five, of the cancer risks faced by a patient of a particular age and sex who is going to undergo a particular radiotherapeutic regimen. It is also possible to make an estimate of the risks faced by radiotherapy and nursing staff exposed to low doses. Brachytherapy related risk estimates are likely to be somewhat more uncertain, due to the poorly known sparing effects of the low dose rates used; for the radiotherapy personnel in brachytherapy, because of the doses which can be received, the risks can be quite significant. A recent complication in external-beam radiotherapy is the advent of high-energy linacs, which can produce a significant fast neutron dose which, dose for dose, may be ten to fifty times more carcinogenic than gamma rays. Data relating to the risks of hereditary effects of radiation come almost entirely from laboratory experiments in animals. Studies involving several million mice form the basis of most of our current understanding of hereditary effects. The results of these studies indicate that radiation is a relatively inefficient mutagen. The

Dose dependent effect of progesterone on hypoxic ventilatory response in newborn rats.

Science.gov (United States)

Hichri, Oubeidallah; Laurin, Jean-C; Julien, Cécile A; Joseph, Vincent; Bairam, Aida

2012-01-01

The effect of progesterone as a respiratory stimulant in newborn subjects is less known than that in adults. This study investigated the dose-response curve (0, 2, 4, and 8 mg/kg, ip) of progesterone on ventilation in non-anesthetized newborn rats at 4- and 12-days old using plethysmography. Progesterone had no effects in the regulation of normoxic ventilation. However, it enhanced the response to moderate hypoxia (FiO(2) 12%, 20 min) in 4- but not in 12-days old pups. This response was similar between the dose of 4 and 8 mg/kg. These observations suggested that progesterone enhances in age- and dose-dependent manner the hypoxic ventilatory response in newborn rats.

Long-term effects of pediatric extracorporeal shockwave lithotripsy on renal function

Directory of Open Access Journals (Sweden)

Akin Y

2014-04-01

Full Text Available Yigit Akin,1 Selcuk Yucel21Department of Urology, Harran University School of Medicine, Sanliurfa, Turkey; 2Department of Urology, Acibadem University School of Medicine, Istanbul, TurkeyIntroduction: Extracorporeal shock wave lithotripsy (ESWL is a well-known and successful treatment modality. In addition, it can be used in premature infants. ESWL is used to treat kidney and ureter stones in children. However, although it is a preferred noninvasive treatment in that setting, there is debate about its long-term effects on growing kidneys in children.Objectives: To investigate the long-term effects of pediatric ESWL on renal function in light of updated literature.Methods: PubMed and Medline were searched for studies on ESWL in a pediatric population with keywords including efficacy, child, kidney calculi, ureter calculi, lithotripsy, injury, vascular trauma, and shock waves. The research was limited to the English literature during a period from 1980 to 2014. In total, 3,000 articles were evaluated, but only 151 papers were considered. Only the manuscripts directly related to the reviewed subjects were included in the current study.Results: However, the acute effects of ESWL in kidney are well-described. Although there are limited studies on the long-term effects of ESWL in children, there is a widespread opinion that ESWL is not affecting renal functions in the long-term.Conclusion: ESWL is a safe, effective, and noninvasive treatment option in children. Although ESWL can cause some acute effects in the kidney, there is no long-term effect on the growing kidneys of children.Keywords: child, lithotripsy, nephrolithiasis, renal injury, vascular trauma

Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy

International Nuclear Information System (INIS)

Safdieh, Joseph; Schwartz, David; Weiner, Joseph; Weiss, Jeffrey P.; Madeb, Isaac; Rotman, Marvin; Schreiber, David; Rineer, Justin

2014-01-01

To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.

Long term radiological impact of thorium extraction

International Nuclear Information System (INIS)

Menard, S.; Schapira, J.P.

1995-01-01

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 232 Th 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 228 Ra, 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 220 Rn. 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

Long-term effects of di-octyl phthalate on the expression of immune-related genes in Tegillarca granosa

Science.gov (United States)

Wang, Ji; Li, Ye; Dai, Juan; Su, Xiurong; Li, Chenghua; Shen, Lingling

2016-05-01

Di-octyl phthalate (DOP) is widely used as a plasticizer in the plastics industry. As a result, DOP is often found in marine water ecosystems where many species are exposed to it. Our objective was to evaluate the effect of long-term (14 d) DOP exposure (2.6, 7.8, or 31.2 mg/L) on the expression of immunerelated genes in Tegillarca granosa. The expression of small heat shock protein (sHSPs) and tissue inhibitor of metalloproteinase (TIMP) were highest in clams exposed to 31.2 mg/L DOP on days 7 and 14. The relative expression of Tg-ferritin, superoxide dismutase (SOD), and metallothionein (MT) increased initially then decreased as the concentration of DOP increased. The hemoglobin of T. granosa (Tg-HbI) exhibited two distinct expression patterns at two time points. Our results suggest that the immune response of T. granosa against DOP pollution varies depending on the dose. Additionally, we identified some immune-related genes that are promising candidates for biomarkers of DOP.

Impact peculiarities of long-term gamma-irradiation with low-dose rate on the development of laboratory rats and their sperm production

International Nuclear Information System (INIS)

Klepko, A.V.; Motrina, O.A.; Vatlyitsova, O.S.; And Others

2015-01-01

The experiments were performed on laboratory white rats of 2.5 months in age. Animals were irradiated in gamma-field of 'Ethalon' device in a dose range 0.1-1.0 Gy. Testicles, epididymices, ventral prostate were retrieved from decapitated animal, each organ weight being determined for every exposure dose. Sperm quantities in testicles and epididymices were identified with aid of phase-contrast microscopy after tissue homogenization in saline containing Triton X-100 and NaN_3. Kinetic characteristics of spermatozoa were analyzed by video recording at 37 C. The longterm gamma-irradiation with low dose rate was shown to cause no effect on the dynamics of animal weight and weight of epididymices changes. However the testes weight was noticed to diminish at doses 0.1, 0.3, 0.6 and 1.0 Gy, the latter dose being stimulative for the ventral prostate growth and weight accumulation. Total sperm quantities in testicles and epididymices along with daily sperm production declined in gamma-irradiated rats compared to control. However curvilinear and straight line spermatozoid velocity as well as the frequency of tail oscillations tended to increase. Long-term gamma-irradiation of the rat whole body with low dose rate just insignificantly affects the development of testes and ventral prostate. Apart from this, radiation effects showed up in sperm production slight suppression, from the on hand, and sperm velocity along with tail oscillations intensification, from the other hand

Assessment of the potential for long-term toxicological effects of the Exxon Valdez oil spill on birds and mammals

International Nuclear Information System (INIS)

Hartung, R.

1995-01-01

This paper assesses the potential for direct long-term toxicological effects of exposures to oils in birds and mammals by tracing exposures and effects form the initial cute phases through the sub-chronic to the eventual long-term exposures. The immediate effects of oil spills are physical, the oil acting on the plumage of birds or the fur of mammals. This causes a loss of entrained air and a concomitant reduction in buoyancy and thermal insulation. Animals that escape the immediate impacts may be isolated from their food supply and often ingest large amounts of oil while attempting to clean themselves. At the comparatively high dose levels involved, these exposures can result in toxicologically significant responses in many organ systems. In the course of an oil pollution incident, the amounts of biologically available oils decrease steadily, and simultaneously the composition of the oils shifts towards those components that have low volatility, and that resist photo- and bio-degradation. As this occurs, the primary pathways of exposure change from direct intakes to indirect routes involving the food supply. Although laboratory studies often report finding some adverse effects, the dose rates employed in many of these studies are extremely high when compared with those that are potentially available to animals in the wild, and very few actually use weathered oils. An assessment of the toxicological literature and of the available empirical data on the Exxon Valdez oil spill leads to the conclusion that long-term sub-lethal toxic effects of crude oils on wildlife in such marine spills appear to be very unlikely. 111 refs., 4 figs., 1 tab

Augmented Reality in Informal Learning Environments: Investigating Short-term and Long-term Effects

DEFF Research Database (Denmark)

Sommerauer, Peter; Müller, Oliver

2018-01-01

field experiment with 24 participants at a mathematics exhibition to measure the effect of AR on acquiring and retaining mathematical knowledge in an informal learning environment, both short-term (i.e., directly after visiting the exhibition) and long-term (i.e., two months after the museum visit). Our...

Long-term Effect of Sodium Oxybate (Xyrem®) in Spasmodic Dysphonia with Vocal Tremor

Science.gov (United States)

Simonyan, Kristina; Frucht, Steven J.

2013-01-01

Background Symptoms of spasmodic dysphonia (SD) are usually managed successfully with botulinum toxin injections. Vocal tremor (VT), which accompanies SD, has a poor response to this treatment. Case Report We report a case of a female with SD and VT who became symptom-free for 10 months after the intake of a single dose of sodium oxybate (Xyrem®). The long-term treatment effect correlated with attenuated brain activity in the key regions of dystonic brain network. Discussion Our case demonstrates that the novel treatment of sodium oxybate may hold promise for SD patients, especially those who have associated VT. PMID:24386608

Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study.

Science.gov (United States)

Marincek, Nicolas; Jörg, Ann-Catherine; Brunner, Philippe; Schindler, Christian; Koller, Michael T; Rochlitz, Christoph; Müller-Brand, Jan; Maecke, Helmut R; Briel, Matthias; Walter, Martin A

2013-01-15

We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1-4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1-158) months, 34 (range: 1-118) months and 29 (range: 1-113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211).

Effects of low doses of short-term gamma irradiation on growth and development through two generations of Pisum sativum

International Nuclear Information System (INIS)

Zaka, R.; Misset, M.T.; Chenal, C.

2004-01-01

The effects of short-term gamma radiation on pea plants were investigated by exposing 5-day-old seedlings with doses ranging from 0 to 60 Gy, and studying plant growth and development over two generations after irradiation. Doses higher than 6 Gy significantly inhibited the G1 plant growth and productivity, and no seedling survived irradiation with 40 Gy and above. These effects were transmitted and were even more severe in the next generation, G2. Irradiated G1 (≥10 Gy) and G2 (≥0.4 Gy) plants were significantly smaller than controls. The mean number of pods produced per plant was reduced by at least 20% at all doses in both G1 and G2. In parallel, the mean numbers of ovules and normally developed seeds per pod were significantly reduced after 10 Gy in G1 and after 0.4 Gy in G2, leading to a significant drop in seed production. This effect was correlated with a linear decrease in male fertility linked to abnormal meiosis (tetrads with micronuclei) as a function of doses from 0 to 10 Gy, in G1 and G2 plants. These long-term changes in plant development demonstrate a genomic instability induced by irradiation. However, there were neither quantitative nor qualitative changes in storage proteins in G1 seeds at any of the irradiation doses tested from 0 to 10 Gy

Quantifying the Combined Effect of Radiation Therapy and Hyperthermia in Terms of Equivalent Dose Distributions

International Nuclear Information System (INIS)

Kok, H. Petra; Crezee, Johannes; Franken, Nicolaas A.P.; Stalpers, Lukas J.A.; Barendsen, Gerrit W.; Bel, Arjan

2014-01-01

Purpose: To develop a method to quantify the therapeutic effect of radiosensitization by hyperthermia; to this end, a numerical method was proposed to convert radiation therapy dose distributions with hyperthermia to equivalent dose distributions without hyperthermia. Methods and Materials: Clinical intensity modulated radiation therapy plans were created for 15 prostate cancer cases. To simulate a clinically relevant heterogeneous temperature distribution, hyperthermia treatment planning was performed for heating with the AMC-8 system. The temperature-dependent parameters α (Gy −1 ) and β (Gy −2 ) of the linear–quadratic model for prostate cancer were estimated from the literature. No thermal enhancement was assumed for normal tissue. The intensity modulated radiation therapy plans and temperature distributions were exported to our in-house-developed radiation therapy treatment planning system, APlan, and equivalent dose distributions without hyperthermia were calculated voxel by voxel using the linear–quadratic model. Results: The planned average tumor temperatures T90, T50, and T10 in the planning target volume were 40.5°C, 41.6°C, and 42.4°C, respectively. The planned minimum, mean, and maximum radiation therapy doses were 62.9 Gy, 76.0 Gy, and 81.0 Gy, respectively. Adding hyperthermia yielded an equivalent dose distribution with an extended 95% isodose level. The equivalent minimum, mean, and maximum doses reflecting the radiosensitization by hyperthermia were 70.3 Gy, 86.3 Gy, and 93.6 Gy, respectively, for a linear increase of α with temperature. This can be considered similar to a dose escalation with a substantial increase in tumor control probability for high-risk prostate carcinoma. Conclusion: A model to quantify the effect of combined radiation therapy and hyperthermia in terms of equivalent dose distributions was presented. This model is particularly instructive to estimate the potential effects of interaction from different treatment

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.

Promising Long-Term Health-Related Quality of Life After High-Dose-Rate Brachytherapy Boost for Localized Prostate Cancer

International Nuclear Information System (INIS)

Wahlgren, Thomas; Nilsson, Sten; Lennernaes, Bo; Brandberg, Yvonne

2007-01-01

Purpose: To explore the long-term general and disease-specific health-related quality of life (HRQOL) >5 years after combined radiotherapy for localized prostate cancer, including a high-dose-rate brachytherapy boost and hormonal deprivation therapy. Methods and Materials: Of 196 eligible patients with localized prostate cancer (Stage T1-T3a) consecutively treated with curative radiotherapy at our institution between June 1998 and August 2000, 182 (93%) completed the European Organization for Research and Treatment of Cancer Quality of Life questionnaires QLQ-C30 and QLQ-PR25, including specific questions on fecal incontinence >5 years after treatment in September 2005. A comparison with age-matched normative data was done, as well as a longitudinal analysis using HRQOL data from a previous study. Results: The analysis included 158 nonrecurrent patients. Comparisons made with normative data showed that physical and role functioning were significantly better statistically and social functioning was significantly worse. Diarrhea and sleep disturbances were more pronounced and pain less pronounced than in a normal male population. The longitudinal analysis of disease-specific HRQOL showed that urinary urgency and erectile problems persisted 5 years after treatment, and nocturia and hormonally dependent symptoms had declined significantly, with a statistically significant difference. Fecal incontinence was recognized by 25% of patients, of whom 80% considered it a minor problem. Conclusion: More than 5 years after combined radiotherapy, irritative urinary problems and erectile dysfunction remain concerns, although severe bowel disturbance and fecal incontinence seem to be minor problems. Longitudinally, a decline mainly in hormonally dependent symptoms was seen. Minor differences in general HRQOL compared with normative data were observed, possibly including 'response shift' effects

Long-term interactive effects of N addition with P and K availability on N status of Sphagnum.

Science.gov (United States)

Chiwa, Masaaki; Sheppard, Lucy J; Leith, Ian D; Leeson, Sarah R; Tang, Y Sim; Neil Cape, J

2018-06-01

Little information exists concerning the long-term interactive effect of nitrogen (N) addition with phosphorus (P) and potassium (K) on Sphagnum N status. This study was conducted as part of a long-term N manipulation on Whim bog in south Scotland to evaluate the long-term alleviation effects of phosphorus (P) and potassium (K) on N saturation of Sphagnum (S. capillifolium). On this ombrotrophic peatland, where ambient deposition was 8 kg N ha -1 yr -1 , 56 kg N ha -1 yr -1 of either ammonium (NH 4 + , N red ) or nitrate (NO 3 - , N ox ) with and without P and K, were added over 11 years. Nutrient concentrations of Sphagnum stem and capitulum, and pore water quality of the Sphagnum layer were assessed. The N-saturated Sphagnum caused by long-term (11 years) and high doses (56 kg N ha -1 yr -1 ) of reduced N was not completely ameliorated by P and K addition; N concentrations in Sphagnum capitula for N red 56 PK were comparable with those for N red 56, although N concentrations in Sphagnum stems for N red 56 PK were lower than those for N red 56. While dissolved inorganic nitrogen (DIN) concentrations in pore water for N red 56 PK were not different from N red 56, they were lower for N ox 56 PK than for N ox 56 whose stage of N saturation had not advanced compared to N red 56. These results indicate that increasing P and K availability has only a limited amelioration effect on the N assimilation of Sphagnum at an advanced stage of N saturation. This study concluded that over the long-term P and K additions will not offset the N saturation of Sphagnum. Copyright © 2018 Elsevier Ltd. All rights reserved.

Long-term results of golimumab therapy for rheumatoid arthritis. Therapy compliance issues

Directory of Open Access Journals (Sweden)

N. V. Chichasova

2016-01-01

Full Text Available The goal of therapy for rheumatoid arthritis (RA is to suppress inflammation, to prevent or delay destructive changes in the joints, and to normalize functions during the longest monitoring of the course of RA. The data of randomized controlled trials and national registries are of great importance to a clinician. The paper reviews the literature data characterizing the long-term results of RA therapy with the tumor necrosis factor-α inhibitor golimumab (GLM and patient compliance with the therapy. Treatment with GLM at the registered subcutaneous dose of 50 mg once every 4 weeks gives rise to an effect in the vast majority of patients regardless of the type of previous ineffective therapy, the dose of concurrently administered methotrexate, the number of previous ineffective disease-modifying antirheumatic drugs, and the use and nonuse of glucocorticoids. GLM is characterized by a long-term (as long as 5 years effect with suppressed progression of destruction, functional recovery, and satisfactory tolerability with no additional risk for adverse events as the therapy is continued.

Development of a checklist of short-term and long-term psychological symptoms associated with ketamine use.

Science.gov (United States)

Fan, Ni; Xu, Ke; Ning, Yuping; Wang, Daping; Ke, Xiaoyin; Ding, Yi; Sun, Bin; Zhou, Chao; Deng, Xuefeng; Rosenheck, Robert; He, Hongbo

2015-06-25

Ketamine is an increasingly popular drug of abuse in China but there is currently no method for classifying the psychological effects of ketamine in individuals with ketamine dependence. Develop a scale that characterizes the acute and long-term psychological effects of ketamine use among persons with ketamine dependence. We developed a preliminary symptom checklist with 35 dichotomous ('yes' or 'no') items about subjective feelings immediately after ketamine use and about perceived long-term effects of ketamine use that was administered to 187 inpatients with ketamine dependence recruited from two large hospitals in Guangzhou, China. Exploratory factor analysis (EFA) was conducted on a randomly selected half of thesample to reduce the items and to identify underlying constructs. Confirmatory factor analysis (CFA) was conducted on the second half of the sample to assess the robustness of the identified factor structure. Among the 35 symptoms, the most-reported acute effects were 'floating or circling' (94%), 'euphoric when listening to rousing music' (86%), and 'feeling excited, talkative, and full of energy' (67%). The mostreported long-term symptoms were 'memory impairment' (93%), 'personality changes' (86%), and 'slowed reactions' (81%). EFA resulted in a final 22-item scale best modelled by a four-factor model: two factors representing chronic symptoms (social withdrawal and sleep disturbances), one about acute psychoticlike symptoms, and one that combined acute drug-related euphoria and longer-term decreased libido. CFA showed that these 4 factors accounted for 50% of the total variance of the final 22-item scale and that the model fit was fair (Goodness of Fit Index, GIF=83.3%; Root Mean Square Error of Approximation, RMSEA=0.072). A four-factor model including social withdrawal, sleep disturbance, psychotic-like symptoms, and euphoria at the time of drug use provides a fair description of the short-term and long-term psychological symptoms associated with

Long-term modeling on HPV vaccination: do we really need any more?

Science.gov (United States)

Garattini, Livio; Curto, Alessandro; van de Vooren, Katelijne

2015-04-01

The human papillomavirus (HPV) is closely related to cervical cancer. In 2007, the EMA approved two vaccines, a bivalent and a quadrivalent one, launched at three-dose schedules and very high prices worldwide. We describe what happened in the EU and what might change in the near future from an economic perspective. HPV vaccination is now established in most EU countries. The main target group of the programs is girls aged 10-14 years. Many western countries used competitive tendering to purchase the two vaccines, achieving considerable savings. The extension to males has been a hotly debated issue. The sex limitation implies that this vaccination cannot by definition achieve a 'herd immunity' effect. EMA recently approved a two-dose schedule for both vaccines that should lead to savings, although it is hard to predict how the forthcoming nonavalent vaccine will affect the market situation. Several economic evaluations based on long-term models have been published on the HPV vaccination in the recent years, using official list prices as a baseline. Most of these models can be considered mere exercises in long-term forecasting. Recently, further long-term models have been published with two- and three-dose schedules as alternatives, and the nonavalent vaccine. We wonder what added value they give for public policy purposes.

Long-term effects of fluoxetine on glycemic control in obese patients with non-insulin-dependent diabetes mellitus or glucose intolerance

DEFF Research Database (Denmark)

Breum, Leif; Bjerre, U; Bak, J F

1995-01-01

differences (mean +/- SD: F, 10.1 +/- 10.0 kg; P, 9.4 +/- 11.5 kg). Fifteen patients from the F group and 14 from the P group completed the 12-month study without weight loss differences. Glycemic regulation improved along with the weight loss, but with a larger decline in plasma C-peptide and fasting glucose......Fluoxetine (F) is a specific serotonin-reuptake inhibitor that has been shown to promote weight loss and improve glycemic control in obese diabetic patients. To study its long-term metabolic effect, 40 obese patients with non-insulin -dependent diabetes mellitus (NIDDM) or impaired glucose...... tolerance (IGT) were included in a 12-month, randomized, placebo controlled study. Patients were assigned to receive either 60 mg F or placebo (P) daily in conjunction with a 5.0-MJ/d diet (> 50% carbohydrate). Both groups showed a significant weight loss, with a nadir after 6 months without group...

[Long-term psychiatric hospitalizations].

Science.gov (United States)

Plancke, L; Amariei, A

2017-02-01

Long-term hospitalizations in psychiatry raise the question of desocialisation of the patients and the inherent costs. Individual indicators were extracted from a medical administrative database containing full-time psychiatric hospitalizations for the period 2011-2013 of people over 16 years old living in the French region of Nord-Pas-de-Calais. We calculated the proportion of people who had experienced a hospitalization with a duration of 292 days or more during the study period. A bivariate analysis was conducted, then ecological data (level of health-care offer, the deprivation index and the size of the municipalities of residence) were included into a multilevel regression model in order to identify the factors significantly related to variability of long-term hospitalization rates. Among hospitalized individuals in psychiatry, 2.6% had had at least one hospitalization of 292 days or more during the observation period; the number of days in long-term hospitalization represented 22.5% of the total of days of full-time hospitalization in psychiatry. The bivariate analysis revealed that seniority in the psychiatric system was strongly correlated with long hospitalization rates. In the multivariate analysis, the individual indicators the most related to an increased risk of long-term hospitalization were: total lack of autonomy (OR=9.0; 95% CI: 6.7-12.2; P<001); diagnoses of psychological development disorders (OR=9.7; CI95%: 4.5-20.6; P<.001); mental retardation (OR=4.5; CI95%: 2.5-8.2; P<.001): schizophrenia (OR=3.0; CI95%: 1.7-5.2; P<.001); compulsory hospitalization (OR=1.7; CI95%: 1.4-2.1; P<.001); having experienced therapeutic isolation (OR=1.8; CI95%: 1.5-2.1; P<.001). Variations of long-term hospitalization rates depending on the type of establishment were very high, but the density of hospital beds or intensity of ambulatory activity services were not significantly linked to long-term hospitalization. The inhabitants of small urban units had

Introduction of long term cycle of reactor operation

International Nuclear Information System (INIS)

Aoyati, M.; Tanaka, T.

2004-01-01

Introduction of long term cycle of LWR reactor operation at NPP in Japan is considered, and problems of technical, legislative and economical character, increase of power coefficient are discussed. More long term operation period provides decreasing frequency of periodic inspections and reduction of personnel radiation doses. Reliability of fuel, energetic equipment, mechanisms and devices must be taken into account for the decision of technical problems. Consumptions for electric power generation are studied [ru

Dose-Effect Relationships for Adverse Events After Cranial Radiation Therapy in Long-term Childhood Cancer Survivors

International Nuclear Information System (INIS)

Dijk, Irma W.E.M. van; Cardous-Ubbink, Mathilde C.; Pal, Helena J.H. van der; Heinen, Richard C.; Leeuwen, Flora E. van; Oldenburger, Foppe; Os, Rob M. van; Ronckers, Cécile M.; Schouten–van Meeteren, Antoinette Y.N.; Caron, Huib N.; Koning, Caro C.E.; Kremer, Leontien C.M.

2013-01-01

Purpose: To evaluate the prevalence and severity of clinical adverse events (AEs) and treatment-related risk factors in childhood cancer survivors treated with cranial radiation therapy (CRT), with the aim of assessing dose-effect relationships. Methods and Materials: The retrospective study cohort consisted of 1362 Dutch childhood cancer survivors, of whom 285 were treated with CRT delivered as brain irradiation (BI), as part of craniospinal irradiation (CSI), and as total body irradiation (TBI). Individual CRT doses were converted into the equivalent dose in 2-Gy fractions (EQD 2 ). Survivors had received their diagnoses between 1966 and 1996 and survived at least 5 years after diagnosis. A complete inventory of Common Terminology Criteria for Adverse Events grade 3.0 AEs was available from our hospital-based late-effect follow-up program. We used multivariable logistic and Cox regression analyses to examine the EQD 2 in relation to the prevalence and severity of AEs, correcting for sex, age at diagnosis, follow-up time, and the treatment-related risk factors surgery and chemotherapy. Results: There was a high prevalence of AEs in the CRT group; over 80% of survivors had more than 1 AE, and almost half had at least 5 AEs, both representing significant increases in number of AEs compared with survivors not treated with CRT. Additionally, the proportion of severe, life-threatening, or disabling AEs was significantly higher in the CRT group. The most frequent AEs were alopecia and cognitive, endocrine, metabolic, and neurologic events. Using the EQD 2 , we found significant dose-effect relationships for these and other AEs. Conclusion: Our results confirm that CRT increases the prevalence and severity of AEs in childhood cancer survivors. Furthermore, analyzing dose-effect relationships with the cumulative EQD 2 instead of total physical dose connects the knowledge from radiation therapy and radiobiology with the clinical experience

Dose-Effect Relationships for Adverse Events After Cranial Radiation Therapy in Long-term Childhood Cancer Survivors

Energy Technology Data Exchange (ETDEWEB)

Dijk, Irma W.E.M. van, E-mail: i.w.vandijk@amc.uva.nl [Department of Radiation Oncology, Academic Medical Center, Amsterdam (Netherlands); Cardous-Ubbink, Mathilde C. [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands); Pal, Helena J.H. van der [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands); Department of Pediatric Oncology, Emma Children' s Hospital/Academic Medical Center, Amsterdam (Netherlands); Heinen, Richard C. [Department of Pediatric Oncology, Emma Children' s Hospital/Academic Medical Center, Amsterdam (Netherlands); Leeuwen, Flora E. van [Department of Epidemiology, Netherlands Cancer Institute, Amsterdam (Netherlands); Oldenburger, Foppe; Os, Rob M. van [Department of Radiation Oncology, Academic Medical Center, Amsterdam (Netherlands); Ronckers, Cécile M. [Dutch Childhood Oncology Group, Long-term Effects after Childhood Cancer, The Hague (Netherlands); Schouten–van Meeteren, Antoinette Y.N. [Department of Pediatric Oncology, Emma Children' s Hospital/Academic Medical Center, Amsterdam (Netherlands); Caron, Huib N. [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands); Department of Pediatric Oncology, Emma Children' s Hospital/Academic Medical Center, Amsterdam (Netherlands); Koning, Caro C.E. [Department of Radiation Oncology, Academic Medical Center, Amsterdam (Netherlands); Kremer, Leontien C.M. [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands); Department of Pediatric Oncology, Emma Children' s Hospital/Academic Medical Center, Amsterdam (Netherlands)

2013-03-01

Purpose: To evaluate the prevalence and severity of clinical adverse events (AEs) and treatment-related risk factors in childhood cancer survivors treated with cranial radiation therapy (CRT), with the aim of assessing dose-effect relationships. Methods and Materials: The retrospective study cohort consisted of 1362 Dutch childhood cancer survivors, of whom 285 were treated with CRT delivered as brain irradiation (BI), as part of craniospinal irradiation (CSI), and as total body irradiation (TBI). Individual CRT doses were converted into the equivalent dose in 2-Gy fractions (EQD{sub 2}). Survivors had received their diagnoses between 1966 and 1996 and survived at least 5 years after diagnosis. A complete inventory of Common Terminology Criteria for Adverse Events grade 3.0 AEs was available from our hospital-based late-effect follow-up program. We used multivariable logistic and Cox regression analyses to examine the EQD{sub 2} in relation to the prevalence and severity of AEs, correcting for sex, age at diagnosis, follow-up time, and the treatment-related risk factors surgery and chemotherapy. Results: There was a high prevalence of AEs in the CRT group; over 80% of survivors had more than 1 AE, and almost half had at least 5 AEs, both representing significant increases in number of AEs compared with survivors not treated with CRT. Additionally, the proportion of severe, life-threatening, or disabling AEs was significantly higher in the CRT group. The most frequent AEs were alopecia and cognitive, endocrine, metabolic, and neurologic events. Using the EQD{sub 2}, we found significant dose-effect relationships for these and other AEs. Conclusion: Our results confirm that CRT increases the prevalence and severity of AEs in childhood cancer survivors. Furthermore, analyzing dose-effect relationships with the cumulative EQD{sub 2} instead of total physical dose connects the knowledge from radiation therapy and radiobiology with the clinical experience.

Long-term follow-up of psilocybin-facilitated smoking cessation.

Science.gov (United States)

Johnson, Matthew W; Garcia-Romeu, Albert; Griffiths, Roland R

2017-01-01

A recent open-label pilot study (N = 15) found that two to three moderate to high doses (20 and 30 mg/70 kg) of the serotonin 2A receptor agonist, psilocybin, in combination with cognitive behavioral therapy (CBT) for smoking cessation, resulted in substantially higher 6-month smoking abstinence rates than are typically observed with other medications or CBT alone. To assess long-term effects of a psilocybin-facilitated smoking cessation program at ≥12 months after psilocybin administration. The present report describes biologically verified smoking abstinence outcomes of the previous pilot study at ≥12 months, and related data on subjective effects of psilocybin. All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (≥16 months) follow-up, with a mean interval of 30 months (range = 16-57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent. At 12-month follow-up 13 participants (86.7%) rated their psilocybin experiences among the five most personally meaningful and spiritually significant experiences of their lives. These results suggest that in the context of a structured treatment program, psilocybin holds considerable promise in promoting long-term smoking abstinence. The present study adds to recent and historical evidence suggesting high success rates when using classic psychedelics in the treatment of addiction. Further research investigating psilocybin-facilitated treatment of substance use disorders is warranted.

Effect of a Short-Term and Long-Term Melatonin Administration on Mammary Carcinogenesis in Female Sprague-Dawley Rats Influenced by Repeated Psychoemotional Stress

Directory of Open Access Journals (Sweden)

M. Kassayová

2007-01-01

Full Text Available The aim of this study was to evaluate the effect of melatonin (MEL on N-methyl-N-nitrosourea (NMU-induced mammary carcinogenesis in female Sprague-Dawley rats exposed to repeated psychoemotional stress - immobilization in boxes. NMU was applied intraperitoneally in two doses each of 50 mg/kg b.w. between 40 - 50 postnatal days. Melatonin was administered in drinking water at a concentration of 4 μg/ml daily from 15:00 h to 8:00 h. The application was initiated 5 days prior to the fi rst NMU dose and lasted 15 days, i.e. during the promotion phase of tumour development, or long-term until the end of the experiment (week 20. Immobilization (2 h per day began on the third day after the second carcinogen application and lasted for 7 consecutive days. Short-term MEL administration to immobilized animals increased incidence by 22%, decreased tumour frequency per animal by 26% and reduced tumour volume gain (by 21% when compared to the immobilized group without MEL application. Decreased frequency per animal by 28% and more than a 40% decrease in tumour volume gain and cumulative volume were the most pronounced changes in the animals drinking MEL until the end of the experiment. Long-term MEL administration reduced the number and size of mammary tumours more markedly than its short-term administration. Melatonin decreased certain attributes of mammary carcinogenesis in female rats influenced by psychoemotional stress.

Cdk7 Is Required for Activity-Dependent Neuronal Gene Expression, Long-Lasting Synaptic Plasticity and Long-Term Memory

Directory of Open Access Journals (Sweden)

Guiqin He

2017-11-01

Full Text Available In the brain, de novo gene expression driven by learning-associated neuronal activities is critical for the formation of long-term memories. However, the signaling machinery mediating neuronal activity-induced gene expression, especially the rapid transcription of immediate-early genes (IEGs remains unclear. Cyclin-dependent kinases (Cdks are a family of serine/threonine kinases that have been firmly established as key regulators of transcription processes underling coordinated cell cycle entry and sequential progression in nearly all types of proliferative cells. Cdk7 is a subunit of transcriptional initiation factor II-H (TFIIH and the only known Cdk-activating kinase (CAK in metazoans. Recent studies using a novel Cdk7 specific covalent inhibitor, THZ1, revealed important roles of Cdk7 in transcription regulation in cancer cells. However, whether Cdk7 plays a role in the regulation of transcription in neurons remains unknown. In this study, we present evidence demonstrating that, in post-mitotic neurons, Cdk7 activity is positively correlated with neuronal activities in cultured primary neurons, acute hippocampal slices and in the brain. Cdk7 inhibition by THZ1 significantly suppressed mRNA levels of IEGs, selectively impaired long-lasting synaptic plasticity induced by 4 trains of high frequency stimulation (HFS and prevented the formation of long-term memories.

Neighborhood Effects in Temporal Perspective: The Impact of Long-Term Exposure to Concentrated Disadvantage on High School Graduation

Science.gov (United States)

Wodtke, Geoffrey T.; Harding, David J.; Elwert, Felix

2011-01-01

Theory suggests that neighborhood effects depend not only on where individuals live today, but also on where they lived in the past. Previous research, however, usually measures neighborhood context only once and does not account for length of residence, thereby understating the detrimental effects of long-term neighborhood disadvantage. This…

The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users.

Science.gov (United States)

Vandrey, Ryan; Stitzer, Maxine L; Mintzer, Miriam Z; Huestis, Marilyn A; Murray, Jeannie A; Lee, Dayong

2013-02-01

Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked five puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad libitum cannabis use. Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120mg doses. Dronabinol's ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg/day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Antimicrobial stewardship in long term care facilities: what is effective?

Science.gov (United States)

Nicolle, Lindsay E

2014-02-12

Intense antimicrobial use in long term care facilities promotes the emergence and persistence of antimicrobial resistant organisms and leads to adverse effects such as C. difficile colitis. Guidelines recommend development of antimicrobial stewardship programs for these facilities to promote optimal antimicrobial use. However, the effectiveness of these programs or the contribution of any specific program component is not known. For this review, publications describing evaluation of antimicrobial stewardship programs for long term care facilities were identified through a systematic literature search. Interventions included education, guidelines development, feedback to practitioners, and infectious disease consultation. The studies reviewed varied in types of facilities, interventions used, implementation, and evaluation. Comprehensive programs addressing all infections were reported to have improved antimicrobial use for at least some outcomes. Targeted programs for treatment of pneumonia were minimally effective, and only for indicators of uncertain relevance for stewardship. Programs focusing on specific aspects of treatment of urinary infection - limiting treatment of asymptomatic bacteriuria or prophylaxis of urinary infection - were reported to be effective. There were no reports of cost-effectiveness, and the sustainability of most of the programs is unclear. There is a need for further evaluation to characterize effective antimicrobial stewardship for long term care facilities.

Long-term heart function after adjuvant epirubicin chemotherapy for breast cancer

DEFF Research Database (Denmark)

Appel, Jon M; Zerahn, Bo; Møller, Susanne

2012-01-01

Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment.......Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment....

[Effect of Long-Term Application of Agrotechnical Techniques and Crops on Soil Microbial Communities].

Science.gov (United States)

Korvigo, I O; Pershina, E V; Ivanova, E A; Matyuk, N S; Savos'kina, O A; Chirak, E L; Provorov, N A; Andronov, E E

2016-01-01

Effects of long-term application ofvarious fertilizers and crops on soil microbiomes an a long-term field experiment were investigated using the library of the 16S rRNA gene sequences obtained by high-throughput sequencing of the total DNA. The communities exhibited high diversity, with 655 microbial genera belonging to 34 phyla detected (31 bacterial and 3 archaeal ones). For analysis of the effect of the studied factors on community structure, a linear model was developed in order to simplify interpretation of the data of high-throughput sequencing and to obtain biologically important information. Liming was shown to modulate the effect of mineral fertilizers on the structure of microbial populations. The differences in the structure and alpha-diversity of microbial communities were shown to depend more on the crops and liming, rather than on the fertilizers applied. Interaction between the crop factor and liming expressed as an ambiguous effect of liming on the microbiome in the presence of different plants was reliably demonstrated. Thus, in the case of barley and clover, liming resulted in increased taxonomic diversity of the community, while in the case of potato and flax it had an opposite effect.

Long-Term Field Data and Climate-Habitat Models Show That Orangutan Persistence Depends on Effective Forest Management and Greenhouse Gas Mitigation

Science.gov (United States)

Gregory, Stephen D.; Brook, Barry W.; Goossens, Benoît; Ancrenaz, Marc; Alfred, Raymond; Ambu, Laurentius N.; Fordham, Damien A.

2012-01-01

Background Southeast Asian deforestation rates are among the world’s highest and threaten to drive many forest-dependent species to extinction. Climate change is expected to interact with deforestation to amplify this risk. Here we examine whether regional incentives for sustainable forest management will be effective in improving threatened mammal conservation, in isolation and when combined with global climate change mitigation. Methodology/Principal Findings Using a long time-series of orangutan nest counts for Sabah (2000–10), Malaysian Borneo, we evaluated the effect of sustainable forest management and climate change scenarios, and their interaction, on orangutan spatial abundance patterns. By linking dynamic land-cover and downscaled global climate model projections, we determine the relative influence of these factors on orangutan spatial abundance and use the resulting statistical models to identify habitat crucial for their long-term conservation. We show that land-cover change the degradation of primary forest had the greatest influence on orangutan population size. Anticipated climate change was predicted to cause reductions in abundance in currently occupied populations due to decreased habitat suitability, but also to promote population growth in western Sabah by increasing the suitability of presently unoccupied regions. Conclusions/Significance We find strong quantitative support for the Sabah government’s proposal to implement sustainable forest management in all its forest reserves during the current decade; failure to do so could result in a 40 to 80 per cent regional decline in orangutan abundance by 2100. The Sabah orangutan is just one (albeit iconic) example of a forest-dependent species that stands to benefit from sustainable forest management, which promotes conservation of existing forests. PMID:22970145

Long-term effects of tetanus toxoid inoculation on the demography and life expectancy of the Cayo Santiago rhesus macaques.

Science.gov (United States)

Kessler, Matthew J; Hernández Pacheco, Raisa; Rawlins, Richard G; Ruiz-Lambrides, Angelina; Delgado, Diana L; Sabat, Alberto M

2015-02-01

Tetanus was a major cause of mortality in the free-ranging population of rhesus monkeys on Cayo Santiago prior to 1985 when the entire colony was given its first dose of tetanus toxoid. The immediate reduction in mortality that followed tetanus toxoid inoculation (TTI) has been documented, but the long-term demographic effects of eliminating tetanus infections have not. This study uses the Cayo Santiago demographic database to construct comparative life tables 12 years before, and 12 years after, TTI. Life tables and matrix projection models are used to test for differences in: (i) survival among all individuals as well as among social groups, (ii) long-term fitness of the population, (iii) age distribution, (iv) reproductive value, and (v) life expectancy. A retrospective life table response experiment (LTRE) was performed to determine which life cycle transition contributed most to observed changes in long-term fitness of the population post-TTI. Elimination of clinical tetanus infections through mass inoculation improved the health and well-being of the monkeys. It also profoundly affected the population by increasing survivorship and long-term fitness, decreasing the differences in survival rates among social groups, shifting the population's age distribution towards older individuals, and increasing reproductive value and life expectancy. These findings are significant because they demonstrate the long-term effects of eradicating a major cause of mortality at a single point in time on survival, reproduction, and overall demography of a naturalistic population of primates. © 2014 Wiley Periodicals, Inc.

Long-Term Follow-up of a Successfully Treated Case of Congenital Pyridoxine-Dependent Epilepsy

OpenAIRE

Proudfoot, Malcolm; Jardine, Philip; Straukiene, Agne; Noad, Rupert; Parrish, Andrew; Ellard, Sian; Weatherby, Stuart

2013-01-01

Autosomal recessive disorders affecting pyridoxine (vitamin B6) metabolism are a rare but well-recognized cause of neonatal seizures. Antiquitin deficiency, caused by mutations in ALDH7A1, is a disorder of the lysine degradation pathway causing accumulation of an intermediate that complexes with pyridoxal phosphate. Reports of long-term follow-up of neonatal pyridoxine-dependent seizures (PDS) remain scarce and prognostic information is varied. We report a case of PDS in a 47-year-old lady wh...

Low-dose-rate brachytherapy for patients with transurethral resection before implantation in prostate cancer: long-term results

International Nuclear Information System (INIS)

Prada, Pedro J.; Anchuelo, Javier; Blanco, Ana Garcia; Paya, Gema; Cardenal, Juan; Acuña, Enrique; Ferri, Maria; Vazquez, Andres; Pacheco, Maite; Sanchez, Jesica

2016-01-01

Objectives: We analyzed the long-term oncologic outcome for patients with prostate cancer and transurethral resection who were treated using low-dose-rate (LDR) prostate brachytherapy. Methods and Materials: From January 2001 to December 2005, 57 consecutive patients were treated with clinically localized prostate cancer. No patients received external beam radiation. All of them underwent LDR prostate brachytherapy. Biochemical failure was defined according to the 'Phoenix consensus'. Patients were stratified as low and intermediate risk based on The Memorial Sloan Kettering group definition. Results: The median follow-up time for these 57 patients was 104 months. The overall survival according to Kaplan-Meier estimates was 88% (±6%) at 5 years and 77% (±6%) at 12 years. The 5 and 10 years for failure in tumour-free survival (TFS) was 96% and respectively (±2%), whereas for biochemical control was 94% and respectively (±3%) at 5 and 10 years, 98% (±1%) of patients being free of local recurrence. A patient reported incontinence after treatment (1.7%). The chronic genitourinary complains grade I were 7% and grade II, 10%. At six months 94% of patients reported no change in bowel function. Conclusions: The excellent long-term results and low morbidity presented, as well as the many advantages of prostate brachytherapy over other treatments, demonstrates that brachytherapy is an effective treatment for patients with transurethral resection and clinical organ-confined prostate cancer. (author)

Low-dose-rate brachytherapy for patients with transurethral resection before implantation in prostate cancer: long-term results

Energy Technology Data Exchange (ETDEWEB)

Prada, Pedro J.; Anchuelo, Javier; Blanco, Ana Garcia; Paya, Gema; Cardenal, Juan; Acuña, Enrique; Ferri, Maria [Department of Radiation Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria (Spain); Vazquez, Andres; Pacheco, Maite; Sanchez, Jesica [Department of Radiation Physics, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria (Spain)

2016-01-15

Objectives: We analyzed the long-term oncologic outcome for patients with prostate cancer and transurethral resection who were treated using low-dose-rate (LDR) prostate brachytherapy. Methods and Materials: From January 2001 to December 2005, 57 consecutive patients were treated with clinically localized prostate cancer. No patients received external beam radiation. All of them underwent LDR prostate brachytherapy. Biochemical failure was defined according to the 'Phoenix consensus'. Patients were stratified as low and intermediate risk based on The Memorial Sloan Kettering group definition. Results: The median follow-up time for these 57 patients was 104 months. The overall survival according to Kaplan-Meier estimates was 88% (±6%) at 5 years and 77% (±6%) at 12 years. The 5 and 10 years for failure in tumour-free survival (TFS) was 96% and respectively (±2%), whereas for biochemical control was 94% and respectively (±3%) at 5 and 10 years, 98% (±1%) of patients being free of local recurrence. A patient reported incontinence after treatment (1.7%). The chronic genitourinary complains grade I were 7% and grade II, 10%. At six months 94% of patients reported no change in bowel function. Conclusions: The excellent long-term results and low morbidity presented, as well as the many advantages of prostate brachytherapy over other treatments, demonstrates that brachytherapy is an effective treatment for patients with transurethral resection and clinical organ-confined prostate cancer. (author)

Forced migration in childhood: Are there long-term health effects?

Directory of Open Access Journals (Sweden)

Jan M. Saarela

2016-12-01

Full Text Available Studies on the health of migrants have increased considerably in number in recent years, but little is still known about the long-term health effects associated with forced migration, and particularly for people who were forced to migrate as children. Data shortcomings together with the methodological challenges of studying migrant populations limit the ability to disentangle the roles of various factors that influence migrant health outcomes. Finland provides an unusual opportunity to study long-term health consequences associated with forced migration. During World War II, twelve per cent of the Finnish population was forced to leave the region nowadays referred to as Ceded Karelia. After the war, these Karelians could not return home because the area was relinquished to the Soviet Union. Using high quality, linked register-based data for the period 1988–2012, we investigate whether this forced migration had long-term health consequences for those who were forced to migrate as children. Comparison groups are non-displaced persons born on the adjacent side of the new border, and people born elsewhere in Finland. Health at ages 43–65 years is measured by receipt of sickness benefit, which is an indicator of short-term illness, and receipt of disability pension, which reflects long-term illness or permanent disability. All-cause and cause-specific mortality is analysed at ages 43–84 years. We find no support for the hypothesis that the traumatic event of being forced to migrate during childhood has long-term negative health consequences. The forced child migrants have lower odds for receipt of sickness benefit, and women also have lower odds for receipt of disability pension. The mortality results are largely driven by patterns specific for eastern-born populations of Finland. A likely reason behind the absence of negative health consequences is that these migrants seem to have integrated well into post-war Finnish society. Keywords

Assessing long-term and rare adverse effects of medicines

NARCIS (Netherlands)

Duijnhoven, R.G.|info:eu-repo/dai/nl/357218574

2016-01-01

Clinical studies in the development of new medicines are primarily designed to investigate efficacy. Knowledge of adverse effects is therefore limited at the time of approval of new medicines. In this thesis several studies were conducted to investigate long-term and rare adverse effects of

Differential role of calpain-dependent protein cleavage in intermediate and long-term operant memory in Aplysia.

Science.gov (United States)

Lyons, Lisa C; Gardner, Jacob S; Lentsch, Cassidy T; Gandour, Catherine E; Krishnan, Harini C; Noakes, Eric J

2017-01-01

In addition to protein synthesis, protein degradation or protein cleavage may be necessary for intermediate (ITM) and long-term memory (LTM) to remove molecular constraints, facilitate persistent kinase activity and modulate synaptic plasticity. Calpains, a family of conserved calcium dependent cysteine proteases, modulate synaptic function through protein cleavage. We used the marine mollusk Aplysia californica to investigate the in vivo role of calpains during intermediate and long-term operant memory formation using the learning that food is inedible (LFI) paradigm. A single LFI training session, in which the animal associates a specific netted seaweed with the failure to swallow, generates short (30min), intermediate (4-6h) and long-term (24h) memory. Using the calpain inhibitors calpeptin and MDL-28170, we found that ITM requires calpain activity for induction and consolidation similar to the previously reported requirements for persistent protein kinase C activity in intermediate-term LFI memory. The induction of LTM also required calpain activity. In contrast to ITM, calpain activity was not necessary for the molecular consolidation of LTM. Surprisingly, six hours after LFI training we found that calpain activity was necessary for LTM, although this is a time at which neither persistent PKC activity nor protein synthesis is required for the maintenance of long-term LFI memory. These results demonstrate that calpains function in multiple roles in vivo during associative memory formation. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute and long-term Purkinje cell loss following a single ethanol binge during the early third trimester equivalent in the rat.

Science.gov (United States)

Idrus, Nirelia M; Napper, Ruth M A

2012-08-01

In the rat, binge-like ethanol (EtOH) exposure during the early neonatal period (a developmental period equivalent to the human third trimester) can result in a permanent deficit of cerebellar Purkinje cells (Pcells). However, the consequences of a moderate binge alcohol exposure on a single day during this postnatal period have not been established. This is an issue of importance as many pregnant women binge drink periodically at social drinking levels. This study aimed to identify both the acute and long-term effects of exposure to a single alcohol binge that achieved a mean peak blood EtOH concentration of approximately 250 mg/dl during early postnatal life using a rat model of fetal alcohol spectrum disorders. Acute apoptotic Pcell death 10 hours after a moderate dose binge EtOH exposure from postnatal days (PDs) 0 to 10 was assessed using active caspase-3 immunolabeling. Acute Pcell apoptosis was quantified in cerebellar vermal lobules I-X using the physical disector method. Long-term effects were assessed at PD 60 using stereological methods to determine total Pcell numbers in the vermis, lobule III, and lobule IX, following a moderate dose binge EtOH exposure at PDs 0, 2, or 4. Acute apoptosis was induced by EtOH on PDs 1 to 8 in a time and lobular-dependent manner. For EtOH exposure on PD 2, significant long-term Pcell loss occurred in lobule III. EtOH exposure on PD 4 resulted in significant long-term Pcell loss throughout the entire vermis. These results indicate that a single, early EtOH episode of moderate dose can create significant and permanent Pcell loss in the developing cerebellum. Copyright © 2012 by the Research Society on Alcoholism.

Few long-term consequences after prolonged maternal separation in female Wistar rats.

Directory of Open Access Journals (Sweden)

Stina Lundberg

Full Text Available Environmental factors during the early-life period are known to have long-term consequences for the adult phenotype. An intimate interplay between genes and environment shape the individual and may affect vulnerability for psychopathology in a sex-dependent manner. A rodent maternal separation model was here used to study the long-term effects of different early-life rearing conditions on adult behavior, HPA axis activity and long-term voluntary alcohol intake in female rats. Litters were subjected to 15 min (MS15 or 360 min (MS360 of daily maternal separation during postnatal day 1-21. In adulthood, the behavioral profiles were investigated using the multivariate concentric square field™ (MCSF test or examined for HPA axis reactivity by cat-odor exposure with subsequent characterization of voluntary alcohol intake and associated changes in HPA axis activity. Adult female MS360 offspring showed mostly no, or only minor, effects on behavior, HPA axis reactivity and long-term alcohol intake relative to MS15. Instead, more pronounced effects were found dependent on changes in the natural hormonal cycle or by the choice of animal supplier. However, changes were revealed in corticosterone load after long-term alcohol access, as females subjected to MS360 had higher concentrations of fecal corticosterone. The present findings are in line with and expand on previous studies on the long-term effects of maternal separation in female rats with regard to behavior, HPA axis activity and voluntary alcohol intake. It can also be a window into further studies detailing how early-life experiences interact with other risk and protective factors to impact the adult phenotype and how possible sex differences play a role.

Long-term effects of acoustic reafference training (ART).

Science.gov (United States)

Pizzera, Alexandra; Hohmann, Tanja; Streese, Lukas; Habbig, Anja; Raab, Markus

2017-11-01

In sport visual feedback is often used to enhance performance, mostly neglecting the auditory modality. However, athletes produce natural sounds when they move (acoustic reafferences) which they perceive and use to control their movements. We examined the short- and long-term effects of a training intervention on a complex movement by using acoustic reafferences. Natural step sounds produced during hurdling were recorded and played back to the participants immediately before each trial, with an increase (fast group), decrease (slow group), or no manipulation (control group) in the tempo. All groups increased their hurdling performance regarding overall running time, with the slow group showing the best performance development. After a 10-week retention, the fast and slow group further increased performance, whereas the control group declined. The repeated experience with acoustic information associated with the rhythmic pattern of hurdling may have helped developing a cognitive representation of that movement, especially regarding long-term effects.

Long-term effects of ionizing radiation after the Chernobyl accident: Possible contribution of historic dose.

Science.gov (United States)

Omar-Nazir, Laila; Shi, Xiaopei; Moller, Anders; Mousseau, Timothy; Byun, Soohyun; Hancock, Samuel; Seymour, Colin; Mothersill, Carmel

2018-08-01

The impact of the Chernobyl NPP accident on the environment is documented to be greater than expected, with higher mutation rates than expected at the current, chronic low dose rate. In this paper we suggest that the historic acute exposure and resulting non-targeted effects (NTE) such as delayed mutations and genomic instability could account at least in part for currently measured mutation rates and provide an initial test of this concept. Data from Møller and Mousseau on the phenotypic mutation rates of Chernobyl birds 9-11 generations post the Chernobyl accident were used and the reconstructed dose response for mutations was compared with delayed reproductive death dose responses (as a measure of genomic instability) in cell cultures exposed to a similar range of doses. The dose to birds present during the Chernobyl NPP accident was reconstructed through the external pathway due to Cs-137 with an estimate of the uncertainty associated with such reconstruction. The percentage of Chernobyl birds several generations after the accident without mutations followed the general shape of the clonogenic survival percentage of the progeny of irradiated cells, and it plateaued at low doses. This is the expected result if NTE of radiation are involved. We suggest therefore, that NTE induced by the historic dose may play a role in generating mutations in progeny many generations following the initial disaster. Copyright © 2018 Elsevier Inc. All rights reserved.

Conditioning radium needles for long term storage : Sri Lankan experience

International Nuclear Information System (INIS)

Ranjith, H.L.A.; Shantha, T.H.S.; Gunaratne, M.G.J.; De Silva, U.W.K.H.; Perera, H.P.H.

2000-01-01

Radium the first radioisotope invented by Madame Curie was used for cancer therapy for the intracavitory treatment of cervical cancers and as oral implants etc. Radium needles and other geometries were made in standard strengths and Radium therapy enjoyed a heyday during the 1st half of the 20th century. Radium-226 is a long-lived radioactive material with a half-life of 1600 years. The use of radium was abandoned in the world in 1980s with the invention of short lived radioactive materials offering remote after loading systems which minimise radiation protection and waste disposal problems associated with long lived radioactive materials. This paper reports the conditioning procedure of the spent radium sources for long term storage (less than 20 years) and transport to national/ international stores if needed. The dose received by those involved in this exercise is also discussed in terms of radiation protection. The Ra was contained for long term storage according to international radiation safety regulations with a surface dose of less than 2 mSv per hour in a conditioned package having 17.5 GBq activity and can be transported to national/international stores if needed. The highest dose received during the exercise is well within the recommended dose limits for occupational exposures (20 and 500 mSv per year) for whole body and extremities respectively

Short-term and long-term effects of violent media on aggression in children and adults

NARCIS (Netherlands)

Bushman, B.J.; Huesmann, L.R.

2006-01-01

Objectives: To test whether the results of the accumulated studies on media violence and aggressive behavior are consistent with the theories that have evolved to explain the effects. We tested for the existence of both short-term and long-term effects for aggressive behavior. We also tested the

Effect of modafinil on learning performance and neocortical long-term potentiation in rats.

Science.gov (United States)

Burgos, Héctor; Castillo, Amparo; Flores, Osvaldo; Puentes, Gustavo; Morgan, Carlos; Gatica, Arnaldo; Cofré, Christian; Hernández, Alejandro; Laurido, Claudio; Constandil, Luis

2010-10-30

Modafinil is a novel wake-promoting agent whose effects on cognitive performance have begun to be addressed at both preclinical and clinical level. The present study was designed to investigate in rats the effects of chronic modafinil administration on cognitive performance by evaluating: (i) working and reference memories in an Olton 4×4 maze, and (ii) learning of a complex operant conditioning task in a Skinner box. In addition, the effect of modafinil on the ability of the rat frontal cortex to develop long-term potentiation (LTP) was also studied. Chronic modafinil did not significantly modify working memory errors but decreased long-term memory errors on the Olton 4×4 maze, meaning that the drug may have a favourable profile on performance of visuo-spatial tasks (typically, a hippocampus-dependent task) when chronically administered. On the other hand, chronic modafinil resulted in a marked decrease of successful responses in a complex operant conditioning learning, which means that repeated administration of the drug influences negatively problem-solving abilities when confronting the rat to a sequencing task (typically, a prefrontal cortex-dependent task). In addition, in vivo electrophysiology showed that modafinil resulted in impaired capacity of the rat prefrontal cortex to develop LTP following tetanization. It is concluded that modafinil can improve the performance of spatial tasks that depend almost exclusively on hippocampal functioning, but not the performance in tasks including a temporal factor where the prefrontal cortex plays an important role. The fact that modafinil together with preventing operant conditioning learning was also able to block LTP induction in the prefrontal cortex, suggests that the drug could interfere some critical component required for LTP can be developed, thereby altering neuroplastic capabilities of the prefrontal cortex. Copyright © 2010 Elsevier Inc. All rights reserved.

Long-term outcomes after disease activity-guided dose reduction of TNF inhibition in rheumatoid arthritis: 3-year data of the DRESS study - a randomised controlled pragmatic non-inferiority strategy trial

NARCIS (Netherlands)

Bouman, Chantal Am; van Herwaarden, Noortje; van den Hoogen, Frank Hj; Fransen, Jaap; van Vollenhoven, Ronald F.; Bijlsma, Johannes Wj; Maas, Aatke van der; den Broeder, Alfons A.

2017-01-01

Tumour necrosis factor inhibitors (TNFi) are effective in rheumatoid arthritis (RA), but disadvantages include adverse events (AEs) and high costs. This can be improved by disease activity-guided dose reduction (DR). We aimed to assess long-term outcomes of TNFi DR in RA by using 3-year data from

Long-term outcomes after disease activity-guided dose reduction of TNF inhibition in rheumatoid arthritis: 3-year data of the DRESS study - a randomised controlled pragmatic non-inferiority strategy trial

NARCIS (Netherlands)

Bouman, C.A.M.; Herwaarden, N. van; Hoogen, F.H.J. van den; Fransen, J.; Vollenhoven, R.F. van; Bijlsma, J.W.; Maas, A.V.; Broeder, A.A. den

2017-01-01

OBJECTIVE: Tumour necrosis factor inhibitors (TNFi) are effective in rheumatoid arthritis (RA), but disadvantages include adverse events (AEs) and high costs. This can be improved by disease activity-guided dose reduction (DR). We aimed to assess long-term outcomes of TNFi DR in RA by using 3-year

Life-long diseases need life-long treatment: long-term safety of ciclosporin in canine atopic dermatitis

Science.gov (United States)

Nuttall, Tim; Reece, Douglas; Roberts, Elizabeth

2014-01-01

Ciclosporin (Atopica; Novartis Animal Health) has been licensed for canine atopic dermatitis (AD) since 2002. Adverse events (AEs) have been reported in 55 per cent of 759 dogs in 15 clinical trials, but are rare in pharmacovigilance data (71.81 AEs/million capsules sold). Gastrointestinal reactions were most common, but were mild and rarely required intervention. Other AEs were rare (≤1 per cent in clinical trials; metabolism is not clinically significant for normal dogs. Concomitant treatment with most drugs is safe. Effects on cytochrome P450 and MDR1 P-glycoprotein activity may elevate plasma ciclosporin concentrations, but short-term changes are not clinically significant. Monitoring of complete blood counts, urinalysis or ciclosporin levels is not justified except with higher than recommended doses and/or long-term concurrent immunosuppressive drugs. Ciclosporin is not a contraindication for killed (including rabies) vaccines, but the licensed recommendation is that live vaccination is avoided during treatment. In conclusion, ciclosporin has a positive risk-benefit profile for the long-term management of canine AD. PMID:24682696

Long-Term Effects of School Size on Students' Outcomes

DEFF Research Database (Denmark)

Humlum, Maria Knoth; Smith, Nina

We estimate the effect of school size on students' long-term outcomes such as high school completion, being out of the labor market, and earnings at the age of 30. We use rich register data on the entire population of Danish children attending grade 9 in the period 1986-2004. This allows us...... school size and alternative measures of long-term success in the educational system and the labor market. The positive impact of school size seems mainly to be driven by boys, students from families with a low educational level and students attending schools in urban areas....

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.

Critical mid-term uncertainties in long-term decarbonisation pathways

International Nuclear Information System (INIS)

Usher, Will; Strachan, Neil

2012-01-01

Over the next decade, large energy investments are required in the UK to meet growing energy service demands and legally binding emission targets under a pioneering policy agenda. These are necessary despite deep mid-term (2025–2030) uncertainties over which national policy makers have little control. We investigate the effect of two critical mid-term uncertainties on optimal near-term investment decisions using a two-stage stochastic energy system model. The results show that where future fossil fuel prices are uncertain: (i) the near term hedging strategy to 2030 differs from any one deterministic fuel price scenario and is structurally dissimilar to a simple ‘average’ of the deterministic scenarios, and (ii) multiple recourse strategies from 2030 are perturbed by path dependencies caused by hedging investments. Evaluating the uncertainty under a decarbonisation agenda shows that fossil fuel price uncertainty is very expensive at around £20 billion. The addition of novel mitigation options reduces the value of fossil fuel price uncertainty to £11 billion. Uncertain biomass import availability shows a much lower value of uncertainty at £300 million. This paper reveals the complex relationship between the flexibility of the energy system and mitigating the costs of uncertainty due to the path-dependencies caused by the long-life times of both infrastructures and generation technologies. - Highlights: ► Critical mid-term uncertainties affect near-term investments in UK energy system. ► Deterministic scenarios give conflicting near-term actions. ► Stochastic scenarios give one near-term hedging strategy. ► Technologies exhibit path dependency or flexibility. ► Fossil fuel price uncertainty is very expensive, biomass availability uncertainty is not.

Marijuana effects on long-term memory assessment and retrieval.

Science.gov (United States)

Darley, C F; Tinklenberg, J R; Roth, W T; Vernon, S; Kopell, B S

1977-05-09

The ability of 16 college-educated male subjects to recall from long-term memory a series of common facts was tested during intoxication with marijuana extract calibrated to 0.3 mg/kg delta-9-tetrahydrocannabinol and during placebo conditions. The subjects' ability to assess their memory capabilities was then determined by measuring how certain they were about the accuracy of their recall performance and by having them predict their performance on a subsequent recognition test involving the same recall items. Marijuana had no effect on recall or recognition performance. These results do not support the view that marijuana provides access to facts in long-term storage which are inaccessible during non-intoxication. During both marijuana and placebo conditions, subjects could accurately predict their recognition memory performance. Hence, marijuana did not alter the subjects' ability to accurately assess what information resides in long-term memory even though they did not have complete access to that information.

Determination of Effect of Low Dose Vs Moderate Dose of Clofibrate on the Decreasing in Serum Bilirubin Level in the Term Healthy Neonate

OpenAIRE

Mohammad Ashkan Moslehi; Narges Pishva

2007-01-01

Objective: This study was performed to determine the effect of low doses (25 mg/Kg) vs. moderate doses (50 mg/Kg) of clofibrate in treatment of non-hemolytic hyperbilirubin¬emia in healthy term neonates. Material & Methods: A clinical randomized controlled trial was performed in three groups of healthy term neonates. One group was treated with a single low dose of clofibrate (25 mg/Kg) while another group received a single moderate dose (50mg/kg) both orally plus phototherapy; the results wer...

Long-term deconditioning of gas-filled surge arresters

Science.gov (United States)

Stanković, Koviljka; Brajović, Dragan; Alimpijević, Mališa; Lončar, Boris

2016-07-01

The aim of this paper is to identify parameters that influence the long-term deconditioning effect of gas-filled surge arrester (GFSA) and to provide practical recommendations for mitigating this effect. Namely, after some period of time, on order of hours or days, during which there is no activation due to overvoltage, the deconditioning of GFSA occurs. This effect was observed experimentally within the paper. The observed parameters that could influence the long-term deconditioning effect were the following: shape of voltage load, gas type, gas pressure, interelectrode distance, electrode material, electrode surface topography as well as GFSA design such as two- or three-electrode configuration. According to the results obtained, it has been shown that the occurrence of long-term deconditioning in an insulating system, insulated by a noble gas at a subpressure and with small interelectrode distances, is a phenomenon that always occurs when the insulating system is at rest for about an hour. It has been found that the type of noble gas does not influence the long-term deconditioning. Analysis of such insulating systems' parameters, with a prospect of being used as GFSAs, has demonstrated that this phenomenon is less pronounced at higher pressures (for the same value of the pressure (p) and interelectrode distance (d) product) and for electrodes with microscopically embossed surfaces. According to the results that were obtained by noble gases and their mixtures, as well as the results that were obtained by mixtures of SF6 gas with noble gasses, it can be claimed with confidence that the effect of the long-term deconditioning is an electrode effect. It has also been established that the deconditioning effect does not depend on the electrode material except in the case of electrodes made out of noble metals, which reduce the effect. Based on these results, it can be recommended that the working point of GFSAs be set (according to the DC breakdown voltage value) at a

Sex work involvement among women with long-term opioid injection drug dependence who enter opioid agonist treatment.

Science.gov (United States)

Marchand, Kirsten; Oviedo-Joekes, Eugenia; Guh, Daphne; Marsh, David C; Brissette, Suzanne; Schechter, Martin T

2012-01-25

Substitution with opioid-agonists (e.g., methadone) has shown to be an effective treatment for chronic long-term opioid dependency. Survival sex work, very common among injection drug users, has been associated with poor Opioid Agonist Treatment (OAT) engagement, retention and response. Therefore, this study was undertaken to determine factors associated with engaging in sex work among long-term opioid dependent women receiving OAT. Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI), conducted in Vancouver and Montreal (Canada) between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone to injectable diacetylmorphine or injectable hydromorphone, the last two on a double blind basis, over 12 months. A research team, independent of the clinic services, obtained outcome evaluations at baseline and follow-up (3, 6, 9, 12, 18 and 24 months). A total 53.6% of women reported engaging in sex work in at least one of the research visits. At treatment initiation, women who were younger and had fewer years of education were more likely to be engaged in sex work. The multivariate logistic generalized estimating equation regression analysis determined that psychological symptoms, and high illicit heroin and cocaine use correlated with women's involvement in sex work during the study period. After entering OAT, women using injection drugs and engaging in sex work represent a particularly vulnerable group showing poorer psychological health and a higher use of heroin and cocaine compared to women not engaging in sex work. These factors must be taken into consideration in the planning and provision of OAT in order to improve treatment outcomes. NCT00175357.

Sex work involvement among women with long-term opioid injection drug dependence who enter opioid agonist treatment

Directory of Open Access Journals (Sweden)

Marchand Kirsten

2012-01-01

Full Text Available Abstract Background Substitution with opioid-agonists (e.g., methadone has shown to be an effective treatment for chronic long-term opioid dependency. Survival sex work, very common among injection drug users, has been associated with poor Opioid Agonist Treatment (OAT engagement, retention and response. Therefore, this study was undertaken to determine factors associated with engaging in sex work among long-term opioid dependent women receiving OAT. Methods Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI, conducted in Vancouver and Montreal (Canada between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone to injectable diacetylmorphine or injectable hydromorphone, the last two on a double blind basis, over 12 months. A research team, independent of the clinic services, obtained outcome evaluations at baseline and follow-up (3, 6, 9, 12, 18 and 24 months. Results A total 53.6% of women reported engaging in sex work in at least one of the research visits. At treatment initiation, women who were younger and had fewer years of education were more likely to be engaged in sex work. The multivariate logistic generalized estimating equation regression analysis determined that psychological symptoms, and high illicit heroin and cocaine use correlated with women's involvement in sex work during the study period. Conclusions After entering OAT, women using injection drugs and engaging in sex work represent a particularly vulnerable group showing poorer psychological health and a higher use of heroin and cocaine compared to women not engaging in sex work. These factors must be taken into consideration in the planning and provision of OAT in order to improve treatment outcomes. Trial Registration NCT00175357.

The dependence of radiation response on the dose per fraction

International Nuclear Information System (INIS)

Joiner, M.C.

1989-01-01

The linear-quadratic (LQ) model explains the dependence of total dose in a fractionated course on the dose per fraction, in a very wide range of tumour and normal tissue studies, providing the dose per fraction remains above 2 Gy. In the range 2-1 Gy per fraction, some experimental studies show less increase in total dose than predicted by LQ; a probable explanation is incomplete repair between fractions given 2 seen between 1 and 0.1 Gy per fraction. This cannot be explained by incomplete repair; a modified LQ model where α decreases sharply with increasing dose per fraction in the range 0-1 Gy fits these data. The basic LQ model describes data from neutron fractionation studies, so the relationship between relative biological effectiveness (RBE) and X-ray dose per fraction can be expressed in terms of LQ parameters and fitted directly to RBE data. Results from different experiments, different assays and both top-up and full-course fractionation techniques, can all be included in one analysis. (author)

Calcium/Calmodulin-dependent Protein Kinase II is a Ubiquitous Molecule in Human Long-term Memory Synaptic Plasticity: A Systematic Review

Science.gov (United States)

Ataei, Negar; Sabzghabaee, Ali Mohammad; Movahedian, Ahmad

2015-01-01

Background: Long-term memory is based on synaptic plasticity, a series of biochemical mechanisms include changes in structure and proteins of brain's neurons. In this article, we systematically reviewed the studies that indicate calcium/calmodulin kinase II (CaMKII) is a ubiquitous molecule among different enzymes involved in human long-term memory and the main downstream signaling pathway of long-term memory. Methods: All of the observational, case–control and review studies were considered and evaluated by the search engines PubMed, Cochrane Central Register of Controlled Trials and ScienceDirect Scopus between 1990 and February 2015. We did not carry out meta-analysis. Results: At the first search, it was fined 1015 articles which included “synaptic plasticity” OR “neuronal plasticity” OR “synaptic density” AND memory AND “molecular mechanism” AND “calcium/calmodulin-dependent protein kinase II” OR CaMKII as the keywords. A total of 335 articles were duplicates in the databases and eliminated. A total of 680 title articles were evaluated. Finally, 40 articles were selected as reference. Conclusions: The studies have shown the most important intracellular signal of long-term memory is calcium-dependent signals. Calcium linked calmodulin can activate CaMKII. After receiving information for learning and memory, CaMKII is activated by Glutamate, the most important neurotransmitter for memory-related plasticity. Glutamate activates CaMKII and it plays some important roles in synaptic plasticity modification and long-term memory. PMID:26445635

Respiratory alkalosis and associated electrolytes in long-term ventilator dependent persons with tetraplegia.

Science.gov (United States)

Watt, J W; Silva, P

2001-11-01

A pilot case control study of the acid-base and electrolyte status in 30 long-term ventilator-dependent (LTVD) and 30 self ventilating persons with tetraplegia. To assess the extent of respiratory alkalosis and screen for associated hypokalaemia, hypomagnesaemia and/or hypophosphataemia. Medically stable persons with tetraplegia under the long-term care of the Southport Spinal Injuries Centre, England. Blood gases and electrolytes were sampled from 30 control patients with tetraplegia and from 30 patients having been LTVD for more than 12 months. All the blood gas measurements in the LTVD group lay outside both the reference range and the 95% confidence intervals (CI) of the control group: pH 7.46 (0.06); PCO(2) 3.46 (1.1) kPa; bicarbonate 18.3 (3.8) and base excess -3.2 (2.8) mmol/l; PO(2) 13.8 (2.8) kPa (means and standard deviations). The serum potassium, magnesium, phosphate, and sodium means lay within the reference ranges but the potassium, phosphate and calcium were at or below the 95% CI of the control values. One patient on part-time ventilatory support having less bicarbonate compensation had low serum electrolytes during ventilation. There was no evidence of biochemical jeopardy from long-term mechanical hyperventilation although acutely administered hyperventilation has the potential to cause falls in serum potassium, magnesium and phosphate and so caution should be exercised in part-time ventilated persons. The full range of electrolytes should be assayed during stabilisation in LTVD and periodically thereafter. Hyperventilation helps to maintain good oxygenation in LTVD persons with paralysis and normal lungs. None.

Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

Directory of Open Access Journals (Sweden)

Marincek Nicolas

2013-01-01

Full Text Available Abstract Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle, 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158 months, 34 (range: 1–118 months and 29 (range: 1–113 months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59 vs. intermediate dose, p = 0.03 and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79 vs. low dose, p = 0.03. Conclusions Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211.

Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

Science.gov (United States)

2013-01-01

Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158) months, 34 (range: 1–118) months and 29 (range: 1–113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Conclusions Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. Trial registration ClinicalTrials.gov number:NCT00978211 PMID:23320604

Effect of aromatherapy massage on elderly patients under long-term hospitalization in Japan.

Science.gov (United States)

Satou, Tadaaki; Chikama, Mizuki; Chikama, Yoshiko; Hachigo, Masato; Urayama, Haruna; Murakami, Shio; Hayashi, Shinichiro; Koikem, Kazuo

2013-03-01

To verify the effectiveness of aromatherapy massage on elderly patients under long-term hospitalization. Aromatherapy massage was performed twice a week for a total of eight times. Nursing home. Elderly women under long-term hospitalization. Questionnaire and measurement of stress marker levels (salivary amylase activity) before and after the first, fifth, and eighth aromatherapy massages. Questionnaire (Face scale, General Health Questionnaire-12 [GHQ-12]), measurement of salivary amylase activity. A decrease in stress after aromatherapy massage compared to before each massage was confirmed at all measurement times and with the stress marker. No marked reduction was observed in Face scale or saliva amylase activity as a whole over the long term, although decreasing tendencies were seen. Marked reductions in GHQ-12 were observed over the long term. Aroma massage appears likely to prove effective in reducing psychological stress among elderly patients under long-term hospitalization.

Cancer risk of low dose/low dose rate radiation: a meta-analysis of cancer data of mammals exposed to low doses of radiation

International Nuclear Information System (INIS)

Ogata, Hiromitsu; Magae, Junji

2008-01-01

Full text: Linear No Threshold (LNT) model is a basic theory for radioprotection, but the adaptability of this hypothesis to biological responses at low doses or at low dose rates is not sufficiently investigated. Simultaneous consideration of the cumulative dose and the dose rate is necessary for evaluating the risk of long-term exposure to ionizing radiation at low dose. This study intends to examine several numerical relationships between doses and dose rates in biological responses to gamma radiation. Collected datasets on the relationship between dose and the incidence of cancer in mammals exposed to low doses of radiation were analysed using meta-regression models and modified exponential (MOE) model, which we previously published, that predicts irradiation time-dependent biological response at low dose rate ionizing radiation. Minimum doses of observable risk and effective doses with a variety of dose rates were calculated using parameters estimated by fitting meta-regression models to the data and compared them with other statistical models that find values corresponding to 'threshold limits'. By fitting a weighted regression model (fixed-effects meta-regression model) to the data on risk of all cancers, it was found that the log relative risk [log(RR)] increased as the total exposure dose increased. The intersection of this regression line with the x-axis denotes the minimum dose of observable risk. These estimated minimum doses and effective doses increased with decrease of dose rate. The goodness of fits of MOE-model depended on cancer types, but the total cancer risk is reduced when dose rates are very low. The results suggest that dose response curve for cancer risk is remarkably affected by dose rate and that dose rate effect changes as a function of dose rate. For scientific discussion on the low dose exposure risk and its uncertainty, the term 'threshold' should be statistically defined, and dose rate effects should be included in the risk

Carbohydrate metabolism during long-term growth hormone (GH) treatment and after discontinuation of GH treatment in girls with Turner syndrome participating in a randomized dose-response study. Dutch Advisory Group on Growth Hormone

NARCIS (Netherlands)

T.C.J. Sas (Theo); S.M.P.F. de Muinck Keizer-Schrama (Sabine); Th. Stijnen (Theo); H-J. Aanstoot (Henk-Jan); S.L.S. Drop (Stenvert)

2000-01-01

textabstractTo assess possible side-effects of GH treatment with supraphysiological doses on carbohydrate (CH) metabolism in girls with Turner syndrome (TS) during long term GH treatment and after discontinuation of GH treatment, the results of oral glucose tolerance

Osteomalacia and Fanconi's syndrome caused by long-term low-dose adefovir dipivoxil.

Science.gov (United States)

Wang, B-F; Wang, Y; Wang, B-Y; Sun, F-R; Zhang, D; Chen, Y-S

2015-06-01

Adefovir dipivoxil (ADV) is recommended for patients infected with lamivudine-refractory hepatitis B virus (HBV). We report a case of low-dose ADV-induced hypophosphatemic osteomalacia that initially presented as diffuse musculoskeletal pain. A 59-year-old Chinese man reported an 18-month history of severe chest wall pain and multiple bone pain during the previous 4 months with no antecedent trauma. There was no clinical evidence of an infectious, inflammatory or malignant process. Medical history showed that the patient had a history of chronic hepatitis B infection, and receiving lamivudine at a daily dose of 100 mg for 70 months. Lamivudine was changed to adefovir (10 mg/day) for the past 42 months. His serum inorganic phosphorus concentration was significantly low (0·4 mmol/l; 0·81-1·5 mmol/L), and the result of a urine routine test was abnormal. Combined with unbearable bone pain, spontaneous fractures, changes in laboratory markers and the result of ECT and other radiographic findings, the diagnosis of Fanconi's syndrome with osteomalacia was established. Dramatic clinical, laboratory and imaging improvement was observed after ADV discontinuation. This case indicates that Fanconi's syndrome with osteomalacia can be acquired by a chronic hepatitis B patient taking ADV at a conventional dosage of 10 mg/day. Therefore, patients with HBV treated with long-term ADV should be regularly monitored for renal function, serum calcium and serum phosphate. Urine testing for ion concentration should also be undertaken. © 2015 John Wiley & Sons Ltd.

Short-Term Effects of Drying-Rewetting and Long-Term Effects of Nutrient Loading on Periphyton N:P Stoichiometry

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Andres D. Sola

2018-01-01

Full Text Available Nitrogen (N and phosphorus (P concentrations and N:P ratios critically influence periphyton productivity and nutrient cycling in aquatic ecosystems. In coastal wetlands, variations in hydrology and water source (fresh or marine influence nutrient availability, but short-term effects of drying and rewetting and long-term effects of nutrient exposure on periphyton nutrient retention are uncertain. An outdoor microcosm experiment simulated short-term exposure to variation in drying-rewetting frequency on periphyton mat nutrient retention. A 13-year dataset from freshwater marshes of the Florida Everglades was examined for the effect of long-term proximity to different N and P sources on mat-forming periphyton nutrient standing stocks and stoichiometry. Field sites were selected from one drainage with shorter hydroperiod and higher connectivity to freshwater anthropogenic nutrient supplies (Taylor Slough/Panhandle, TS/Ph and another drainage with longer hydroperiod and higher connectivity to marine nutrient supplies (Shark River Slough, SRS. Total P, but not total N, increased in periphyton mats exposed to both low and high drying-rewetting frequency with respect to the control mats in our experimental microcosm. In SRS, N:P ratios slightly decreased downstream due to marine nutrient supplies, while TS/Ph increased. Mats exposed to short-term drying-rewetting had higher nutrient retention, similar to nutrient standing stocks from long-term field data. Periphyton mat microbial communities may undergo community shifts upon drying-rewetting and chronic exposure to nutrient loads. Additional work on microbial species composition may further explain how periphyton communities interact with drying-rewetting dynamics to influence nutrient cycling and retention in wetlands.

Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization

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Thanos Manos

2018-04-01

Full Text Available In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce

Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization.

Science.gov (United States)

Manos, Thanos; Zeitler, Magteld; Tass, Peter A

2018-01-01

In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR) stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS) robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate) is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS) turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce long-term

Dose-dependent hepatic transcriptional responses in Atlantic salmon (Salmo salar) exposed to sublethal doses of gamma radiation

Energy Technology Data Exchange (ETDEWEB)

Song, You, E-mail: you.song@niva.no [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo (Norway); Salbu, Brit; Teien, Hans-Christian; Heier, Lene Sørlie [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Rosseland, Bjørn Olav [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian University of Life Sciences (NMBU), Department of Ecology and Natural Resource Management, P.O. Box 5003, N-1432 Ås (Norway); Tollefsen, Knut Erik [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo (Norway)

2014-11-15

Highlights: • First study on early stress responses in salmon exposed to low-dose gamma radiation. • Dramatic dose-dependent transcriptional responses characterized. • Multiple modes of action proposed for gamma radiation. - Abstract: Due to the production of free radicals, gamma radiation may pose a hazard to living organisms. The high-dose radiation effects have been extensively studied, whereas the ecotoxicity data on low-dose gamma radiation is still limited. The present study was therefore performed using Atlantic salmon (Salmo salar) to characterize effects of low-dose (15, 70 and 280 mGy) gamma radiation after short-term (48 h) exposure. Global transcriptional changes were studied using a combination of high-density oligonucleotide microarrays and quantitative real-time reverse transcription polymerase chain reaction (qPCR). Differentially expressed genes (DEGs; in this article the phrase gene expression is taken as a synonym of gene transcription, although it is acknowledged that gene expression can also be regulated, e.g., at protein stability and translational level) were determined and linked to their biological meanings predicted using both Gene Ontology (GO) and mammalian ortholog-based functional analyses. The plasma glucose level was also measured as a general stress biomarker at the organism level. Results from the microarray analysis revealed a dose-dependent pattern of global transcriptional responses, with 222, 495 and 909 DEGs regulated by 15, 70 and 280 mGy gamma radiation, respectively. Among these DEGs, only 34 were commonly regulated by all radiation doses, whereas the majority of differences were dose-specific. No GO functions were identified at low or medium doses, but repression of DEGs associated with GO functions such as DNA replication, cell cycle regulation and response to reactive oxygen species (ROS) were observed after 280 mGy gamma exposure. Ortholog-based toxicity pathway analysis further showed that 15 mGy radiation

Effectiveness of India ink as a long-term colonic mucosal marker.

Science.gov (United States)

Fennerty, M B; Sampliner, R E; Hixson, L J; Garewal, H S

1992-01-01

We prospectively studied the use of India ink as a long-term or "permanent" mucosal marker as part of a study investigating the natural history of diminutive distal colorectal polyps. Twenty-six patients had 32 India ink tatoos implanted. The tatoo sites of the 19 patients who were followed at least 6 months continued to display intensely stained mucosa at the original sites. No side effects or complications were encountered. India ink appears to be a safe and effective long-term marker for colonic mucosal lesions.

A novel nicotinic agonist facilitates induction of long-term potentiation in the rat hippocampus.

Science.gov (United States)

Hunter, B E; de Fiebre, C M; Papke, R L; Kem, W R; Meyer, E M

1994-02-28

Long-term potentiation (LTP) can be modulated by a number of neurotransmitter receptors including muscarinic and GABAergic receptor types. We have found that a novel nicotinic agonist, 2,4-dimethoxybenzylidene anabaseine (DMXB), facilitated the induction of LTP in the hippocampus in a dose-dependent and mecamylamine-sensitive manner. DMXB displaced high affinity nicotinic [125I]alpha-bungarotoxin and [3H]acetylcholine binding in rat brain. Xenopus oocyte studies demonstrated that DMXB has agonist activity at alpha 7 but not alpha 4/beta 2 nicotinic receptor subtypes. These results indicated that DMXB is a novel nicotinic agonist with apparent specificity for the alpha 7/alpha-bungarotoxin nicotinic receptor subtype and indicate that nicotinic receptor activation is capable of modulating the induction of long-term potentiation.

Role of Proteasome-Dependent Protein Degradation in Long-Term Operant Memory in "Aplysia"

Science.gov (United States)

Lyons, Lisa C.; Gardner, Jacob S.; Gandour, Catherine E.; Krishnan, Harini C.

2017-01-01

We investigated the in vivo role of protein degradation during intermediate (ITM) and long-term memory (LTM) in "Aplysia" using an operant learning paradigm. The proteasome inhibitor MG-132 inhibited the induction and molecular consolidation of LTM with no effect on ITM. Remarkably, maintenance of steady-state protein levels through…

Radiosurgery of craniopharyngiomas. Results of long-term follow-up

International Nuclear Information System (INIS)

Kida, Yoshihisa; Hasegawa, Toshinori; Yoshimoto, Masayuki; Koike, Johzi; Kobayashi, Tatsuya

2007-01-01

Long-term follow-up results of craniopharyngiomas after radiosurgery are reported. Among 125 cases of craniopharyngioma, long-term follow-up more than 6 months is obtained in 108 cases. Majority of the cases have had surgical excision before radiosurgery. The tumors, 19 mm in mean diameter were treated with the mean maximum dose of 22.1 Gy and with the marginal dose of 11.6 Gy. The final radiological outcomes during 63 months of mean follow-up showed 9 complete responses (CRs), 61 partial responses (PRs), 1 minor response (MR), 19 no changes (NCs) and 18 PGs, indicating the response rate of 65% and the control rate of 83% respectively. Neurological and endocrinological signs were improved in 18%, unchanged in 53% and worsened in 15% of cases, meanwhile 8% of the patients were dead. Small and solid tumors were the best indication for radiosurgery due to excellent tumor control as well as no adverse effects. They may have a good chance for complete remission. In conclusion a sufficient tumor resection with microsurgery is required and subsequent radiosurgery is most adequate for treating craniopharyngiomas. (author)

Effects of long-term exposure to air pollution on natural-cause mortality

DEFF Research Database (Denmark)

Beelen, Rob; Raaschou-Nielsen, Ole; Stafoggia, Massimo

2013-01-01

Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air...... pollutants....

Long-Term Effects of Adderall XR in ADHD

Directory of Open Access Journals (Sweden)

J Gordon Millichap

2005-06-01

Full Text Available The long-term tolerability and effectiveness of extended release mixed amphetamine salts (Adderall XR in children with attention deficit hyperactivity disorder (ADHD were evaluated in a 24-month, multicenter, open-label extension of 2 placebo-controlled studies at UCLA, Massachusetts General Hospital, UC-Irvine, Maitland, FL, and Shire Pharmaceutical, Wayne, PA.

Effects of Acute Exercise on Long-Term Memory

Science.gov (United States)

Labban, Jeffrey D.; Etnier, Jennifer L.

2011-01-01

In this study, we tested the effect of acute exercise on long-term memory, specifically the timing of exercise relative to the memory challenge. We assessed memory via paragraph recall, in which participants listened to two paragraphs (exposure) and recounted them following a 35-min delay. Participants (n = 48) were randomly assigned to one of…

Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory

Science.gov (United States)

Maher, Pamela; Akaishi, Tatsuhiro; Abe, Kazuho

2006-01-01

Small molecules that activate signaling pathways used by neurotrophic factors could be useful for treating CNS disorders. Here we show that the flavonoid fisetin activates ERK and induces cAMP response element-binding protein (CREB) phosphorylation in rat hippocampal slices, facilitates long-term potentiation in rat hippocampal slices, and enhances object recognition in mice. Together, these data demonstrate that the natural product fisetin can facilitate long-term memory, and therefore it may be useful for treating patients with memory disorders. PMID:17050681

Long-term prophylaxis in severe factor VII deficiency.

Science.gov (United States)

Siboni, S M; Biguzzi, E; Mistretta, C; Garagiola, I; Peyvandi, F

2015-11-01

The spectrum of bleeding problems in FVII deficiency is highly variable and FVII levels and causative genetic mutations correlate poorly with the bleeding risk. Long-term prophylaxis is generally initiated in order to prevent subsequent CNS bleeding after a first event or in patients with other major/ life threatening/ frequent bleeding symptoms as gastrointestinal bleeding or hemarthrosis. However few data are available in the literature regarding FVII prophylaxis and clinical decisions cannot be based on evidence. We report the data available in the literature on FVII prophylaxis and our personal experience regarding three patients affected by severe FVII deficiency. Specific papers on long-term prophylaxis in severe FVII deficiency were identified using the database, PUBMED. The most frequent indications for long-term prophylaxis were CNS bleeding (58%), hemartrosis (15%) and GI bleeding (9%). Patients were treated with various dosages and frequency. Prophylactic treatment with 10-30U/kg (pdFVII) or 20-30mcg/kg (rFVIIa) twice or three times/weeks was described to be effective. In the literature and in our experience, prophylaxis can be considered in patients with severe FVII deficiency and severe bleeding phenotype. A dose of 10-30U/kg (pdFVII) or 20-30 microg/kg (rFVIIa) twice or three times/week is usually administrated, but dose and frequency can be tailored based on the clinical follow-up of the patients. Since hemarthrosis is a frequent manifestation, a suggestion to improve the outcomes of patients with severe FVII deficiency is to monitor joint condition in order to identify early arthropathy that could be another indication to start secondary prophylaxis. © 2015 John Wiley & Sons Ltd.

The time-dependent effect of the biological component of 137Cs soil contamination

International Nuclear Information System (INIS)

Dederichs, H.; Pillath, J.; Lennartz, R.; Hill, P.; Hille, R.

2004-01-01

In investigations of the long-term development of the population dose in the highly contaminated regions of the Commonwealth of Independence States it was found that the external dose has not decreased as strongly as expected since 1992. Further investigations have shown that, contrary to expectations, no linear correlation can be observed between soil contamination and measured area dose rate. As a contribution towards clarifying these issues, the area dose rate and the soil contamination including the plant fraction were investigated in the Korma district, Belarus. It was found that it is necessary to cover and average over larger areas in order to determine from ground contamination the long-term development of the external dose commitment. This means that for this purpose the introduction of an ''effective'' surface contamination (sum of mineral and organic contamination components) is necessary. The phenomena observed are described in a model, which permits an analytical calculation of the contamination profile in soil taking migration and transfer effects into account. The differences observed between the measured soil contamination and the resulting external doses or the directly measured dose rate can be explained by the proposed model. Moreover, their long-term development can be calculated. The results show that a time decade after the accident the biological part of the ''effective'' soil contamination becomes dominant and cannot be neglected. (orig.)

Long term effects on potential repository sites: occurrence and diagenesis of anhydrite

International Nuclear Information System (INIS)

Bath, A.H.; George, I.A.; Milodowski, A.E.; Darling, W.G.

1985-10-01

The report deals with the long-term behaviour of anhydrite as a potential host rock for deep disposal of intermediate-level radioactive wastes. The principal long-term effect on the integrity of such a repository is the possibility of penetration of groundwater and consequent transformation to gypsum. Therefore, in order to assess the chydrological and geochemical processes of hydration in detail, mineralogical and geochemical analyses have been carried out on anhydrite samples in a drillcore taken near Darlington, United Kingdom. The results are discussed in terms of the long-term integrity of anhydrite as a repository site. (U.K.)

Long-term health effects among testicular cancer survivors.

Science.gov (United States)

Hashibe, Mia; Abdelaziz, Sarah; Al-Temimi, Mohammed; Fraser, Alison; Boucher, Kenneth M; Smith, Ken; Lee, Yuan-Chin Amy; Rowe, Kerry; Rowley, Braden; Daurelle, Micky; Holton, Avery E; VanDerslice, James; Richiardi, Lorenzo; Bishoff, Jay; Lowrance, Will; Stroup, Antoinette

2016-12-01

Testicular cancer is diagnosed at a young age and survival rates are high; thus, the long-term effects of cancer treatment need to be assessed. Our objectives are to estimate the incidence rates and determinants of late effects in testicular cancer survivors. We conducted a population-based cohort study of testicular cancer survivors, diagnosed 1991-2007, followed up for a median of 10 years. We identified 785 testicular cancer patients who survived ≥5 years and 3323 men free of cancer for the comparison group. Multivariate Cox regression analysis was used to compare the hazard ratio between the cases and the comparison group and for internal analysis among case patients. Testicular cancer survivors experienced a 24 % increase in risk of long-term health effects >5 years after diagnosis. The overall incidence rate of late effects among testicular cancer survivors was 66.3 per 1000 person years. Higher risks were observed among testicular cancer survivors for hypercholesterolemia, infertility, and orchitis. Chemotherapy and retroperitoneal lymph node dissection appeared to increase the risk of late effects. Being obese prior to cancer diagnosis appeared to be the strongest factor associated with late effects. Testicular cancer survivors were more likely to develop chronic health conditions when compared to cancer-free men. While the late effects risk was increased among testicular cancer survivors, the incidence rates of late effects after cancer diagnosis was fairly low.

Long-term dietary supplementation with low-dose nobiletin ameliorates hepatic steatosis, insulin resistance, and inflammation without altering fat mass in diet-induced obesity.

Science.gov (United States)

Kim, Young-Je; Choi, Myung-Sook; Woo, Je Tae; Jeong, Mi Ji; Kim, Sang Ryong; Jung, Un Ju

2017-08-01

We evaluated the long-term effect of low-dose nobiletin (NOB), a polymethoxylated flavone, on diet-induced obesity and related metabolic disturbances. C57BL/6J mice were fed a high-fat diet (HFD, 45 kcal% fat) with or without NOB (0.02%, w/w) for 16 weeks. NOB did not alter food intake or body weight. Despite increases in fatty acid oxidation-related genes expression and enzymes activity in adipose tissue, NOB did not affect adipose tissue weight due to simultaneous increases in lipogenic genes expression and fatty acid synthase activity. However, NOB significantly decreased not only pro-inflammatory genes expression in adipose tissue but also proinflammatory cytokine levels in plasma. NOB-supplemented mice also showed improved glucose tolerance and insulin resistance, along with decreased levels of plasma insulin, free fatty acids, total cholesterol, non-HDL-cholesterol, and apolipoprotein B. In addition, NOB caused significant decreases in hepatic lipid droplet accumulation and triglyceride content by activating hepatic fatty acid oxidation-related enzymes. Hepatic proinflammatory TNF-α mRNA expression, collagen accumulation, and plasma levels of aminotransferases, liver damage indicators, were also significantly lower in NOB-supplemented mice. These findings suggest that long-term supplementation with low-dose NOB can protect against HFD-induced inflammation, insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease, without ameliorating adiposity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Long-term carbimazole pretreatment reduces the efficacy of radioiodine therapy

Directory of Open Access Journals (Sweden)

C Shivaprasad

2015-01-01

Full Text Available Introduction: Data from several studies suggest that pretreatment with antithyroid drugs (ATD before 131 I increases the risk of treatment failure. This effect has been demonstrated more consistently with propylthiouracil than with carbimazole (CMZ or methimazole (MMI. Men with Graves′ disease (GD have a lower rate of remission with 131 I compared to women and the impact of long-term ATD pretreatment on the success of 131 I is unknown. The objective of our study was to compare the efficacy of fixed doses of radioiodine between patients with and without long-term CMZ pretreatment. Materials and Methods: We performed a retrospective study on 335 male patients with GD treated with 131 I from 1998 to 2008. 148 patients had been pretreated with CMZ, and the remaining 187 patients received 131 I without pretreatment. We compared the success rate of a single dose of 131 I, between patients with and without long-term CMZ pretreatment. Results: The success rate of a single dose of 131 I was significantly higher in patients without pretreatment than in patients who were pretreated with CMZ (91.4% vs. 82.3%, P = 0.01. The rate of hypothyroidism in the first 6 months after 131 I therapy was significantly higher in patients without pretreatment (55.1% vs. 44.6%, P = 0.05. There was also a trend for higher cumulative rate of hypothyroidism at last follow-up in nonpretreated patients (78.1% vs. 69.7%. Conclusion: Male patients with Graves′ hyperthyroidism pretreated with CMZ have lower efficacy with 131I therapy compared to nonpretreated patients. CMZ pretreatment given for a prolonged period reduces the efficacy of 131 I therapy.

Long-term effects and quality of life after treatment for rectal cancer

NARCIS (Netherlands)

Wiltink, L.M.

2017-01-01

In this thesis long-term effects and quality of life after treatment for rectal cancer are evaluated. Long-term data were assessed from the TME trial. In this trial 1530 Dutch patients with rectal cancer were included between 1996 and 1999. These patients were randomly assigned to total mesorectal

Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma

DEFF Research Database (Denmark)

Jacobsen, L; Niggemann, B; Dreborg, S

2007-01-01

BACKGROUND: 3-year subcutaneous specific immunotherapy (SIT) in children with seasonal allergic rhinoconjunctivitis reduced the risk of developing asthma during treatment and 2 years after discontinuation of SIT (5-year follow-up) indicating long-term preventive effect of SIT. OBJECTIVE: We......: Specific immunotherapy has long-term clinical effects and the potential of preventing development of asthma in children with allergic rhino conjunctivitis up to 7 years after treatment termination....

The long-term effects of radiation therapy on patients with ovarian dysgerminoma

International Nuclear Information System (INIS)

Mitchell, M.F.; Gershenson, D.M.; Soeters, R.P.; Eifel, P.J.; Delclos, L.; Wharton, J.T.

1991-01-01

A retrospective chart review and questionnaire study was undertaken to look at the long-term effects of radiation therapy in ovarian dysgerminoma patients. Forty-three patients and 55 controls responded to a questionnaire that detailed bowel, bladder, thyroid, menstrual, reproductive, sexual, and growth function. Statistically significant differences in the number of bowel movements were noticed when comparing patients with controls. The authors noticed no significant differences between cases and controls in bladder function. No thyroid disorders were attributable to mediastinal radiation therapy. Most patients with intact uteri bleed monthly on hormonal replacement. Three patients with a remaining ovary and uterus resumed menstrual function after substantial doses of abdominopelvic radiation therapy. No patients have conceived. The authors noticed a slight increase in dyspareunia in the treated group, but most patients were satisfied with their sexual function. One premenarchal patient exhibited a growth disorder

Dienogest in long-term treatment of endometriosis

Directory of Open Access Journals (Sweden)

Schindler AE

2011-07-01

Full Text Available Adolf E SchindlerInstitute for Medical Research and Education, Essen, GermanyAbstract: Endometriosis is a chronic disease primarily affecting women of childbearing age, in which endometriotic lesions form outside the uterus, typically leading to painful symptoms, fatigue, and infertility. The symptoms of endometriosis may cause significant impairment in quality of life and represent a substantial economic burden to patients, families, and society. There is no cure for endometriosis; management consists of alleviating pain and other symptoms, reducing endometriotic lesions, and improving quality of life. Recurrence after surgical intervention is common, while the clinical evidence to support the efficacy and safety of many medications currently used in endometriosis is limited. Dienogest is an oral progestin that has been investigated extensively in the treatment of endometriosis in two clinical programs performed in Europe and Japan, including dose-ranging, placebo-controlled, active comparator-controlled, and long-term (up to 65 weeks studies. These studies demonstrated that dienogest 2 mg daily effectively alleviates the painful symptoms of endometriosis, reduces endometriotic lesions, and improves indices of quality of life. Dienogest showed a favorable safety and tolerability profile in these studies, with predictable adverse effects, high rates of patient compliance, and low withdrawal rates. This review article describes the clinical trial evidence that characterizes the efficacy and safety of dienogest in endometriosis, including two studies characterizing dienogest in long-term use. The relevance of these findings to the management of endometriosis in clinical practice is discussed.Keywords: dienogest, endometriosis, progestins, long-term treatment, quality of life, symptoms, pain

Effects of Cortisol on Short and Long Term Diet and Morphology

DEFF Research Database (Denmark)

Peiman, Kathryn S.; Birnie-Gauvin, Kim; Larsen, Martin Hage

2017-01-01

Glucocorticoids such as cortisol are released during stressful events. However, many of the effects of cortisol on animals in the wild are still poorly documented. We evaluated the effects of artificially elevated cortisol on diet and morphology over the short term (2 weeks) and long term (4 months......) using a wild population of juvenile semi-anadromous brown trout (Salmo trutta) in Denmark. We caught, tagged and manipulated juvenile fish while in their natal freshwater streams in the fall. Manipulations consisted of an exogenous intracoelomic injection of cortisol suspended in vegetable shortening...... using geometric morphometrics. Cortisol affected carbon stable isotope signatures but had minimal effects on nitrogen isotopes and morphology. Irrespective of treatment, carbon and nitrogen stable isotope values increased over time. This study shows that cortisol can have both short and long term...

Colchicine triggered severe rhabdomyolysis after long-term low-dose simvastatin therapy: a case report.

Science.gov (United States)

Frydrychowicz, Clara; Pasieka, Bastian; Pierer, Matthias; Mueller, Wolf; Petros, Sirak; Weidhase, Lorenz

2017-01-04

Rhabdomyolysis is a widely recognized yet rare complication in statin use. Rhabdomyolysis might be triggered by the prescription of high doses of statins or by statin accumulation due to interactions with concomitant medication. Muscle cell destruction as evidenced by myoglobin elevation can induce potentially life-threatening acute renal failure. We report a case of a 70-year-old obese white man with sudden onset of severe rhabdomyolysis with consecutive renal failure. His medication included low-dose simvastatin, which he had taken for 6 years up until the event. The statin was withdrawn immediately. After 3 days of veno-venous hemofiltration his renal function was completely restored. Clinicians in both primary and special care might be unaware that side effects of statins do occur even after a long uneventful statin medication; they should be advised not to exclude that possibility upfront, even if a patient has tolerated the medication for years.

Long-term toxicity of [177Lu-DOTA0,Tyr3]octreotate in rats

International Nuclear Information System (INIS)

Rolleman, Edgar J.; Krenning, Eric P.; Bernard, Bert F.; Visser, Monique de; Bijster, Magda; Jong, Marion de; Visser, Theo J.; Vermeij, Marcel; Lindemans, Jan

2007-01-01

Studies on peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues have shown promising results with regard to tumour control. The efficacy of PRRT is limited by uptake and retention in the proximal tubules of the kidney, which might lead to radiation nephropathy. We investigated the long-term renal toxicity after different doses of [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate and the effects of dose fractionation and lysine co-injection in two tumour-bearing rat models. Significant renal toxicity was detected beyond 100 days after start of treatment as shown by elevated serum creatinine and proteinuria. Microscopically, tubules were strongly dilated with flat epithelium, containing protein cylinders. Creatinine levels rose significantly after 555 MBq [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate, but were significantly lower after 278 MBq (single injection) or two weekly doses of 278 MBq. Renal damage scores were maximal after 555 MBq and significantly lower in the 278 and 2 x 278 MBq groups. Three doses of 185 MBq [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate with intervals of a day, a week or a month significantly influenced serum creatinine (469±18, 134±70 and 65±15 μmol/l, respectively; p 177 Lu-DOTA 0 ,Tyr 3 ]octreotate resulted in severe renal damage in rats as indicated by proteinuria, elevated serum creatinine and histological damage. This damage was dose dependent and became overt between 100 and 200 days after treatment. Dose fractionation had significant beneficial effects on kidney function. Also, lysine co-injection successfully prevented functional damage. (orig.)

Deferasirox: appraisal of safety and efficacy in long-term therapy

Directory of Open Access Journals (Sweden)

Chaudhary P

2013-08-01

Full Text Available Preeti Chaudhary, Vinod PullarkatJane Ann Nohl Division of Hematology, University of Southern California Keck School of Medicine, Los Angeles, CA, USAAbstract: Deferasirox is a once-daily, oral iron chelator that is widely used in the management of patients with transfusional hemosiderosis. Several Phase II trials along with their respective extension studies as well as a Phase III trial have established the efficacy and safety of this novel agent in transfusion-dependent patients with β-thalassemia, sickle-cell disease and bone marrow-failure syndromes, including myelodysplastic syndrome and aplastic anemia. Data from various clinical trials show that a deferasirox dose of 20 mg/kg/day stabilizes serum ferritin levels and liver iron concentration, while a dose of 30–40 mg/kg/day reduces these parameters and achieves negative iron balance in red cell transfusion-dependent patients with iron overload. Across various pivotal clinical trials, deferasirox was well tolerated, with the most common adverse events being gastrointestinal disturbances, skin rash, nonprogressive increases in serum creatinine, and elevations in liver enzyme levels. Longer-term extension studies have also confirmed the efficacy and safety of deferasirox. However, it is essential that patients on deferasirox therapy are monitored regularly to ensure timely management for any adverse events that may occur with long-term therapy.Keywords: deferasirox, iron overload, thalassemia, sickle-cell disease, myelodysplastic syndrome

Prednisolone dose-dependently influences inflammation and coagulation during human endotoxemia

NARCIS (Netherlands)

de Kruif, Martijn D.; Lemaire, Lucienne C.; Giebelen, Ida A.; van Zoelen, Marieke A. D.; Pater, Jennie M.; van den Pangaart, Petra S.; Groot, Angelique P.; de Vos, Alex F.; Elliott, Peter J.; Meijers, Joost C. M.; Levi, Marcel; van der Poll, Tom

2007-01-01

The effects of steroids on the outcome of sepsis are dose dependent. Low doses appear to be beneficial, but high doses do not improve outcome for reasons that are insufficiently understood. The effects of steroids on systemic inflammation as a function of dose have not previously been studied in

Long-term effectiveness of surgical treatment of ectopic atrial tachycardia.

Science.gov (United States)

Prager, N A; Cox, J L; Lindsay, B D; Ferguson, T B; Osborn, J L; Cain, M E

1993-07-01

The purpose of this study was to determine the long-term clinical outcome of patients with ectopic atrial tachycardias treated surgically. Ectopic atrial tachycardia is an uncommon arrhythmia that can be symptomatic and is associated with the development of a cardiomyopathy. Management strategies are not well defined because of the paucity of data on the long-term effectiveness of pharmacologic and nonpharmacologic therapies. The long-term clinical impact of medical and surgical therapy was determined in 15 consecutive patients with ectopic atrial tachycardia. All 15 patients were initially treated with antiarrhythmic drugs (mean 5.7 +/- 2.2 drugs/patient). An effective drug regimen was identified in only 5 (33%) of the 15 patients; the remaining 10 patients were treated surgically. In each, individualized surgical procedures were guided by computer-assisted intraoperative mapping, with atrial plaques comprising up to 156 electrodes. Focal ablation was performed in four patients and atrial isolation procedures in six. The 10 patients treated surgically were followed up a mean of 4 +/- 3.2 years. Ectopic atrial tachycardia recurred in one patient. A permanent pacemaker was implanted in two patients, one of whom also required reoperation for constrictive pericarditis. There were no operative deaths. Ectopic atrial tachycardia recurred in three (60%) of the five patients discharged on antiarrhythmic drug therapy during a mean follow-up interval of 6.4 +/- 4.3 years. There was one nonarrhythmic death. Map-guided surgery demonstrated long-term efficacy in abolishing symptoms in 9 of the 10 patients with ectopic atrial tachycardia. Results demonstrate that surgery is effective for patients with ectopic atrial tachycardias who are not easily treated with antiarrhythmic drugs.

Long-term stability of decontamination effect in recreational areas near the town Novozybkov, Bryansk Region, Russia

International Nuclear Information System (INIS)

Ramzaev, V.; Andersson, K.G.; Barkovsky, A.; Fogh, C.L.; Mishine, A.; Roed, J.

2006-01-01

In 1995 and 1997, experimental decontamination campaigns were carried out in two recreational areas, Novie Bobovichi and Guta-Muravinka, near the town of Novozybkov, Bryansk Region, Russia. These areas were strongly affected by the Chernobyl fallout in 1986. In order to examine the long-term stability of the clean-up procedures, a programme has been carried out to continuously monitor the radiological situation in and around the decontaminated areas. This follow-up program consists of regular (1-3 times per year) measurements of absorbed gamma-dose rate in air (DR) at reference indoor and outdoor locations, repeated DR measurements on a grid, and gamma-spectrometric analysis of soil and other environmental samples. Very similar dynamics of the Chernobyl-related DR, mostly attributed to radiocaesium decay, were found in all the locations. For the period under study (September 1995-May 2003), the half-lives (years) for the reduction in radiocaesium-dependent DR contribution due to contaminant migration (in the following termed 'DRM half-lives') were, respectively, 52 ± 26, 57 ± 23, 43 ± 21, 46 ± 15, and 80 ± 56 for the following locations: untreated outdoors, treated outdoors, untreated indoors, treated indoors, and undisturbed forest-grassland plots outside the recreational areas. These relatively high values of the current DRM half-lives correspond very well with the results of soil core analyses, which showed no time-dependent changes in the mean mass depths of the 137 Cs distribution, neither at treated nor at undisturbed plots. The following signs of natural restoration of the disturbed forest-meadow ecosystems have been observed at treated areas: formation of a new litter layer, development of grassy spots, mushroom growths and new generations of pines and birches. The levels of the 137 Cs content in grass and mushrooms from treated plots were one or two orders of magnitude lower, than those registered in the samples from untreated areas. The follow

Estimation of health effects of long-term chronic exposure of the low level radiation among children exposed in consequence of the disaster at the Chernobyl nuclear power plant

International Nuclear Information System (INIS)

Bomko, E.I.; Romanneko, A.E.; Bomko, A.A.

1997-01-01

The low level dose effects have been studied for a long time within a framework of biological effects of radiation exposure. The estimation of the dose level of Ukrainian people who have been exposed in consequence of the Chernobyl accident allowed to consider that one of the critical populations which had been exposed to the low level radiation were children residing on the areas contaminated with radionuclides. The purpose of this work is - to reveal a regularity in morbidity and mortality of the critical populations having been exposed to long-term chronic exposure of the low level doses of radiation in consequences of the Chernobyl accident

Effects of social instability stress in adolescence on long-term, not short-term, spatial memory performance.

Science.gov (United States)

Green, Matthew R; McCormick, Cheryl M

2013-11-01

There is evidence that exposure to stressors in adolescence leads to lasting deficits on hippocampal-dependent tasks, but whether medial prefrontal cortical function is also impaired is unknown. We previously found that rats exposed to social instability stress in adolescence (SS; daily 1h isolation and subsequent change of cage partner between postnatal days 30 and 45) had impaired memory performance on a Spatial Object Location test and in memory for fear conditioning context, tasks that depend on the integrity of the hippocampus. Here we investigated whether impaired performance would be evident after adolescent SS in male rats on a different test of hippocampal function, spatial learning and memory in the Morris water maze (MWM) and on a working memory task for which performance depends on the integrity of the medial prefrontal cortex, the Delayed Alternation task (DAT). During MWM testing, SS rats showed greater improvements in performance across trials within days compared to control (CTL) rats, but showed less retention of learning between days (48 h) compared to CTL rats. Similarly, SS rats had impaired long-term memory in the Spatial Object Location test after a long delay (240 min), but not after shorter delays (15 or 60 min) compared to CTL rats. No group differences were observed on the DAT, which assessed working memory across brief delays (5-90 s). Thus, deficits in memory performance after chronic social stress in adolescence may be limited to long-term memory. Copyright © 2013 Elsevier B.V. All rights reserved.

How much radiation dose, to whom? Long-term storage, surveillance, retrieval and long processes cause additional dose to employees; Wie viel Strahlendosis fuer wen? Lange Lagerung, Offenhaltung und ein langer Entsorgungsprozess bedeuten zusaetzliche Dosis fuer Beschaeftigte

Energy Technology Data Exchange (ETDEWEB)

Walther, Clemens [Hannover Univ. (Germany). Inst. fuer Radiooekologie und Strahlenschutz; Riemann, Moritz [Kiel Univ. (Germany). Lehrstuhl fuer Philosophie und Ethik der Umwelt

2017-09-01

In the case of final nuclear waste disposal there are concurrent interests with respect to radiation protection: The realization of a disposal option with minimum required follow-up care needs time causing additional radiation exposure for the employees, also the option of long-term storage, surveillance and retrieval possibilities cause additional dose to employees. The contribution discusses possible consideration of requests for the different options.

Long term effects of exposure to ionizing irradiation on periodontal health status – the Tinea Capitis cohort study

Directory of Open Access Journals (Sweden)

Siegal eSadetzki

2015-10-01

Full Text Available Studies among long term survivors of childhood cancer who had received high dose irradiation therapy of 4-60 Gy, demonstrated acute and chronic dental effects including periodontal diseases. However, the possible effects of low to moderate doses of radiation on dental health are sparse. The aim of this study is to investigate the association between childhood exposure to low-moderate doses of ionizing radiation and periodontal health following 50 years from the exposure. The study population included 253 irradiated subjects (treated for Tinea Capitis in the 1950s and, 162 non-irradiated subjects, treated for Tinea Capitis in the 1950s. The estimated dose to the teeth was 0.2-0.4Gy. Dental examination was performed according to the Community Periodontal Index (CPI. Socio-economic and health behavior variables were obtained through a personal questionnaire. Periodontal disease was operationally defined as deep periodontal pockets. A multivariate logistic regression model was used for the association of irradiation status and other independent variables with periodontal status.The results showed that among the irradiated subjects, 23% (95% CI 18%-28% demonstrated complete edentulousness or insufficient teeth for CPI scoring as compared to 13% (95% CI 8%-19% among the non-irradiated subjects (p=0.01. Periodontal disease was detected among 54% of the irradiated subjects as compared to 40% of the non-irradiated (p=0.008. Controlling for education and smoking, the ORs for the association between radiation and periodontal disease were 1.61 (95% CI 1.01-2.57 and 1.95 (95% CI 1.1-3.5 for ever never and per 1 Gy absorbed in the salivary gland, respectively. In line with other studies, a protective effect for periodontal diseases among those with high education and an increased risk for ever smokers were observed. In conclusion, childhood exposure to low-moderate doses of ionizing radiation might be associated with later outcomes of dental health. The

[Accumulative effects and long-term persistence of subliminal mere exposure].

Science.gov (United States)

Kawakami, Naoaki; Yoshida, Fujio

2011-10-01

We examined the accumulative effects and long-term persistence of subliminal mere exposure. An accumulative exposure condition (100 exposures distributed over five days) and a massed exposure condition (100 exposures in one day) were used in a Go/No-go Association Task (GNAT), with assessments of likability from Time 1 (just after) to Time 6 (after three months). First, a single stimulus was shown subliminally for a total of 100 times. The results indicated that mere exposure effects occurred equally often at Time 1. However, after Time 2, likability gradually decreased under the massed exposure condition, while it did not decrease under the accumulative exposure condition until Time 6. Second, in order to investigate the effect of multiple exposure, five stimuli belonging to a common category were shown 20 times each, for a total of 100 times. An ANOVA suggested that massed exposure had an instantaneous effect on likability, whereas accumulative exposure had a long-term persistence effect. Also, multiple exposures strengthened the mere exposure effect.

Different dose-dependent effects of ebselen in sciatic nerve ischemia-reperfusion injury in rats.

Science.gov (United States)

Ozyigit, Filiz; Kucuk, Aysegul; Akcer, Sezer; Tosun, Murat; Kocak, Fatma Emel; Kocak, Cengiz; Kocak, Ahmet; Metineren, Hasan; Genc, Osman

2015-08-26

Ebselen is an organoselenium compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of ebselen pretreatment in rats with experimental sciatic nerve ischemia-reperfusion (I/R) injury. Adult male Sprague Dawley rats were divided into four groups (N = 7 in each group). Before sciatic nerve I/R was induced, ebselen was injected intraperitoneally at doses of 15 and 30 mg/kg. After a 2 h ischemia and a 3 h reperfusion period, sciatic nerve tissues were excised. Tissue levels of malondialdehyde (MDA) and nitric oxide (NO), and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured. Sciatic nerve tissues were also examined histopathologically. The 15 mg/kg dose of ebselen reduced sciatic nerve damage and apoptosis (pebselen. Conversely, the 30 mg/kg dose of ebselen increased sciatic nerve damage, apoptosis, iNOS positive cells (pebselen may cause different effects depending on the dose employed. Ebselen may be protective against sciatic nerve I/R injury via antioxidant and antiapoptotic activities at a 15 mg/kg dose, conversely higher doses may cause detrimental effects.

Nucleic acid metabolism in hemopoietic tissues of polycythemic rats during long-term fractionated irradiation

International Nuclear Information System (INIS)

Mushkacheva, G.S.; Murzina, L.D.

1980-01-01

A study was made of the effect of long-term fractionated exposure with a daily dose of 50 R on the nucleic acid metabolism in hemopoietic tissues (bone marrow and spleen) of rats with erythropoiesis selectively inhibited by posttransfusion polycythemia. The comparison of present and previously obtained results enables us to conclude that the pathways of changes in the nucleic acid metabolism, which is responsible for hemopoiesis compensation during long-term exposure, are, in the main, similar for both white and red compartments of hemopoiesis

Observation of long term potentiation in papain-based memory devices

KAUST Repository

Bag, A.; Hota, Mrinal Kanti; Mallik, Sandipan B.; Maì ti, Chinmay Kumar

2014-01-01

Biological synaptic behavior in terms of long term potentiation has been observed in papain-based (plant protein) memory devices (memristors) for the first time. Improvement in long term potentiation depends on pulse amplitude and width (duration). Continuous/repetitive dc voltage sweep leads to an increase in memristor conductivity leading to a long term memory in the 'learning' processes.

Observation of long term potentiation in papain-based memory devices

KAUST Repository

Bag, A.

2014-06-01

Biological synaptic behavior in terms of long term potentiation has been observed in papain-based (plant protein) memory devices (memristors) for the first time. Improvement in long term potentiation depends on pulse amplitude and width (duration). Continuous/repetitive dc voltage sweep leads to an increase in memristor conductivity leading to a long term memory in the \\'learning\\' processes.

Long-term outcomes of kidney transplantation across a positive complement-dependent cytotoxicity crossmatch.

Science.gov (United States)

Riella, Leonardo V; Safa, Kassem; Yagan, Jude; Lee, Belinda; Azzi, Jamil; Najafian, Nader; Abdi, Reza; Milford, Edgar; Mah, Helen; Gabardi, Steven; Malek, Sayeed; Tullius, Stefan G; Magee, Colm; Chandraker, Anil

2014-06-27

More than 30% of potential kidney transplant recipients have pre-existing anti-human leukocyte antigen antibodies. This subgroup has significantly lower transplant rates and increased mortality. Desensitization has become an important tool to overcome this immunological barrier. However, limited data is available regarding long-term outcomes, in particular for the highest risk group with a positive complement-dependent cytotoxicity crossmatch (CDC XM) before desensitization. Between 2002 and 2010, 39 patients underwent living-kidney transplantation across a positive CDC XM against their donors at our center. The desensitization protocol involved pretransplant immunosuppression, plasmapheresis, and low-dose intravenous immunoglobulin±rituximab. Measured outcomes included patient survival, graft survival, renal function, rates of rejection, infection, and malignancy. The mean and median follow-up was 5.2 years. Patient survival was 95% at 1 year, 95% at 3 years, and 86% at 5 years. Death-censored graft survival was 94% at 1 year, 88% at 3 years, and 84% at 5 years. Uncensored graft survival was 87% at 1 year, 79% at 3 years, and 72% at 5 years. Twenty-four subjects (61%) developed acute antibody-mediated rejection of the allograft and one patient lost her graft because of hyperacute rejection. Infectious complications included pneumonia (17%), BK nephropathy (10%), and CMV disease (5%). Skin cancer was the most prevalent malignancy in 10% of patients. There were no cases of lymphoproliferative disorder. Mean serum creatinine was 1.7±1 mg/dL in functioning grafts at 5 years after transplantation. Despite high rates of early rejection, desensitization in living-kidney transplantation results in acceptable 5-year patient and graft survival rates.

A single low dose of Fe ions can cause long-term biological responses in NL20 human bronchial epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Cao, Qianlin; Wang, Jingdong; Cao, Jianping; Yang, Hongying [Medical College of Soochow University/Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, School of Radiation Medicine and Protection, Suzhou, Jiangsu (China); Liu, Wei [Soochow University, Department of Radiotherapy and Oncology, Second Affiliated Hospital, Suzhou, Jiangsu (China)

2018-03-15

Space radiation cancer risk may be a potential obstacle for long-duration spaceflight. Among all types of cancer space radiation may induce, lung cancer has been estimated to be the largest potential risk. Although previous animal study has shown that Fe ions, the most important contributor to the total dose equivalent of space radiation, induced a higher incidence of lung tumorigenesis per dose than X-rays, the underlying mechanisms at cellular level remained unclear. Therefore, in the present study, we investigated long-term biological changes in NL20 human bronchial epithelial cells after exposure to Fe ion or X-ray irradiation. We found that compared with sham control, the progeny of NL20 cells irradiated with 0.1 Gy of Fe ions showed slightly increased micronucleus formation, significantly decreased cell proliferation, disturbed cell cycle distribution, and obviously elevated intracellular ROS levels accompanied by reduced SOD1 and SOD2 expression, but the progeny of NL20 cells irradiated with 0.9 Gy of X-rays did not show any significant changes. More importantly, Fe ion exposure caused much greater soft-agar colony formation than X-rays did in the progeny of irradiated NL20 cells, clearly suggesting higher cell transformation potential of Fe ions compared with X-rays. These data may shed the light on the potential lung tumorigenesis risk from Fe ion exposure. In addition, ATM inhibition by Ku55933 reversed some of the changes in the progeny of Fe ion-irradiated cells but not others such as soft-agar colony formation, suggesting complex processes from DNA damage to carcinogenesis. These data indicate that even a single low dose of Fe ions can induce long-term biological responses such as cell transformation, etc., suggesting unignorable health risk from space radiation to astronauts. (orig.)

Long-term semantic representations moderate the effect of attentional refreshing on episodic memory.

Science.gov (United States)

Loaiza, Vanessa M; Duperreault, Kayla A; Rhodes, Matthew G; McCabe, David P

2015-02-01

The McCabe effect (McCabe, Journal of Memory and Language 58:480-494, 2008) refers to an advantage in episodic memory (EM) retrieval for memoranda studied in complex span versus simple span tasks, particularly for memoranda presented in earlier serial positions. This finding has been attributed to the necessity to refresh memoranda during complex span tasks that, in turn, promotes content-context binding in working memory (WM). Several frameworks have conceptualized WM as being embedded in long-term memory. Thus, refreshing may be less efficient when memoranda are not well-established in long-term semantic memory (SM). To investigate this, we presented words and nonwords in simple and complex span trials in order to manipulate the long-term semantic representations of the memoranda with the requirement to refresh the memoranda during WM. A recognition test was administered that required participants to make a remember-know decision for each memorandum recognized as old. The results replicated the McCabe effect, but only for words, and the beneficial effect of refreshing opportunities was exclusive to recollection. These results extend previous research by indicating that the predictive relationship between WM refreshing and long-term EM is specific to recollection and, furthermore, moderated by representations in long-term SM. This supports the predictions of WM frameworks that espouse the importance of refreshing in content-context binding, but also those that view WM as being an activated subset of and, therefore, constrained by the contents of long-term memory.

Long-term follow-up of lung biodistribution and effect of instilled SWCNTs using multiscale imaging techniques

International Nuclear Information System (INIS)