GYY4137, an H2S Slow-Releasing Donor, Prevents Nitrative Stress and α-Synuclein Nitration in an MPTP Mouse Model of Parkinson's Disease.

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Hou, Xiaoou; Yuan, Yuqing; Sheng, Yulan; Yuan, Baoshi; Wang, Yali; Zheng, Jiyue; Liu, Chun-Feng; Zhang, Xiaohu; Hu, Li-Fang

2017-01-01

The neuromodulator hydrogen sulfide (H 2 S) was shown to exert neuroprotection in different models of Parkinson's disease (PD) via its anti-inflammatory and anti-apoptotic properties. In this study, we evaluated the effect of an H 2 S slow-releasing compound GYY4137 (GYY) on a mouse PD model induced by acute injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). GYY was intraperitoneally (i.p.) injected once daily into male C57BL/6J mice 3 days before and 2 weeks after MPTP (14 mg/kg, four times at 2-h intervals, i.p.) administration. Saline was given as a control. Behavioral tests (rotarod, balance beam, and grid walking) showed that 50 mg/kg GYY significantly ameliorated MPTP-caused motor impairments. At lower doses (12.5 and 25 mg/kg) GYY exhibited a less obvious effect. Consistent with this, immunohistochemistry and western blot analysis demonstrated that 50 mg/kg GYY attenuated the loss of tyrosine hydroxylase (TH) positive neurons in the substantia nigra and the decrease of TH expression in the striatum of MPTP-treated mice. Moreover, at this regimen GYY relieved the nitrative stress, as indicated by the decreases in nitric oxide (NO) generation and neuronal NO synthase (nNOS) upregulation elicited by MPTP in the striatum. The suppression of GYY on nNOS expression was verified in vitro , and the results further revealed that Akt activation may participate in the inhibition by GYY on nNOS upregulation. More important, GYY reduced the nitrated modification of α-synuclein, a PD-related protein, in MPTP-induced mice. Overall, our findings suggest that GYY attenuated dopaminergic neuron degeneration and reduced α-synuclein nitration in the midbrain, thus exerting neuroprotection in MPTP-induced mouse model of PD.

GYY4137, an H2S Slow-Releasing Donor, Prevents Nitrative Stress and α-Synuclein Nitration in an MPTP Mouse Model of Parkinson’s Disease

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Xiaoou Hou

2017-10-01

Full Text Available The neuromodulator hydrogen sulfide (H2S was shown to exert neuroprotection in different models of Parkinson’s disease (PD via its anti-inflammatory and anti-apoptotic properties. In this study, we evaluated the effect of an H2S slow-releasing compound GYY4137 (GYY on a mouse PD model induced by acute injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP. GYY was intraperitoneally (i.p. injected once daily into male C57BL/6J mice 3 days before and 2 weeks after MPTP (14 mg/kg, four times at 2-h intervals, i.p. administration. Saline was given as a control. Behavioral tests (rotarod, balance beam, and grid walking showed that 50 mg/kg GYY significantly ameliorated MPTP-caused motor impairments. At lower doses (12.5 and 25 mg/kg GYY exhibited a less obvious effect. Consistent with this, immunohistochemistry and western blot analysis demonstrated that 50 mg/kg GYY attenuated the loss of tyrosine hydroxylase (TH positive neurons in the substantia nigra and the decrease of TH expression in the striatum of MPTP-treated mice. Moreover, at this regimen GYY relieved the nitrative stress, as indicated by the decreases in nitric oxide (NO generation and neuronal NO synthase (nNOS upregulation elicited by MPTP in the striatum. The suppression of GYY on nNOS expression was verified in vitro, and the results further revealed that Akt activation may participate in the inhibition by GYY on nNOS upregulation. More important, GYY reduced the nitrated modification of α-synuclein, a PD-related protein, in MPTP-induced mice. Overall, our findings suggest that GYY attenuated dopaminergic neuron degeneration and reduced α-synuclein nitration in the midbrain, thus exerting neuroprotection in MPTP-induced mouse model of PD.

Amphetamine-metabolites of deprenyl involved in protection against neurotoxicity induced by MPTP and 2'-methyl-MPTP.

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Sziráki, I; Kardos, V; Patthy, M; Pátfalusi, M; Gaál, J; Solti, M; Kollár, E; Singer, J

1994-01-01

The ability of 1-deprenyl to protect against the parkinsonian effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been attributed to the inhibition of conversion of MPTP to MPP+ (1-methyl-4-phenylpyridinium) catalyzed by MAO-B. We report here that deprenyl-treatment in mice has an additional neuroprotective element associated with the rapid metabolization of 1-deprenyl to 1-methamphetamine and 1-amphetamine. 1-Methamphetamine and 1-amphetamine inhibit MPP(+)-uptake into striatal synaptosomes prepared from rats. Post-treatment by 1-deprenyl, 1-methamphetamine, 1-amphetamine (at times when MPTP is no longer present in the striatum of mice) protects against neurotoxicity in C57BL mice by blocking the uptake of MPP+ into dopaminergic neurons, and even against the neurotoxicity induced by 2'CH3-MPTP, which is partly bioactivated by MAO-A. These findings may have clinical implications since deprenyl has recently been found to delay the progression of Parkinson's disease.

Neuroprotective Effects of a Variety of Pomegranate Juice Extracts against MPTP-Induced Cytotoxicity and Oxidative Stress in Human Primary Neurons

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Nady Braidy

2013-01-01

Full Text Available 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP is an environmental toxin which selectively induces oxidative damage and mitochondrial and proteasomal dysfunctions to dopaminergic neurons in the substantia nigra leading to Parkinsonian syndrome in animal models and humans. MPTP is one of the most widely used in vitro models to investigate the pathophysiology of Parkinson's disease (PD and, screen for novel therapeutic compounds that can slow down or ameliorate this progressive degenerative disease. We investigated the therapeutic effect of pomegranate juice extracts (PJE, Helow, Malasi, Qusum, and Hamadh against MPTP-induced neurotoxicity in primary human neurons by examining extracellular LDH activity, intracellular NAD+ and ATP levels, and endogenous antioxidant levels including lipid peroxidation products, catalase, superoxide dismutase (SOD and glutathione peroxidase (GPx activities, and reduced glutathione (GSH levels. MPTP induced a reduction in SOD and GPx activities and intracellular NAD+, ATP, and GSH levels parallel to an increase in extracellular LDH and CAT activities, although lipid peroxidation was not altered. We report that helow and malasi can ameliorate MPTP-induced neurotoxicity by attenuating the observed changes in redox function to a greater extent than qusum and hamedh. Selected PJE varieties may exhibit properties which may be of therapeutic value to slow down age-related degeneration and neurodegeneration in particular.

Gypenosides ameliorate memory deficits in MPTP-lesioned mouse model of Parkinson's disease treated with L-DOPA.

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Zhao, Ting Ting; Kim, Kyung Sook; Shin, Keon Sung; Park, Hyun Jin; Kim, Hyun Jeong; Lee, Kyung Eun; Lee, Myung Koo

2017-09-06

Previous studies have revealed that gypenosides (GPS) improve the symptoms of anxiety disorders in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rat model of Parkinson's disease (PD). The present study aimed to investigate the effects of GPS on memory deficits in an MPTP-lesioned mouse model of PD treated with L-3,4-dihydroxyphenylalanine (L-DOPA). MPTP (30 mg/kg/day, 5 days)-lesioned mice were treated with GPS (50 mg/kg) and/or L-DOPA (10 and 25 mg/kg) for 21 days. After the final treatments, behavioral changes were assessed in all mice using passive avoidance and elevated plus-maze tests. We then evaluated the biochemical influences of GPS treatment on levels of tyrosine hydroxylase (TH), dopamine, N-methyl-D-aspartate (NMDA) receptors, extracellular signal-regulated kinase (ERK1/2), and cyclic AMP-response element binding protein (CREB) phosphorylation. MPTP-lesioned mice exhibited deficits associated with habit learning and spatial memory, which were further aggravated by treatment with L-DOPA (25 mg/kg). However, treatment with GPS (50 mg/kg) ameliorated memory deficits. Treatment with GPS (50 mg/kg) also improved L-DOPA (25 mg/kg)-treated MPTP lesion-induced decreases in retention latency on the passive avoidance test, as well as levels of TH-immunopositive cells and dopamine in the substantia nigra and striatum. GPS treatment also attenuated increases in retention transfer latency on the elevated plus-maze test and in NMDA receptor expression, as well as decreases in the phosphorylation of ERK1/2 and CREB in the hippocampus. Treatment with L-DOPA (10 mg/kg) also ameliorated deficits in habit learning and spatial memory in MPTP-lesioned mice, and this effect was further enhanced by treatment with GPS (50 mg/kg). GPS ameliorate deficits in habit learning and spatial memory by modulating the dopaminergic neuronal and N-methyl-D-aspartate receptor-mediated signaling systems in MPTP-lesioned mice treated with L-DOPA. GPS may serve as an adjuvant

Does melatonin help save dopaminergic cells in MPTP-treated mice?

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Ma, Jeannine; Shaw, Victoria E; Mitrofanis, John

2009-05-01

This study explores whether melatonin neuroprotects dopaminergic cells of the substantia nigra pars compacta (SNc) from degeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice (well-known animal model of Parkinson disease). BALB/c albino mice were divided into four experimental groups. In each, mice received three series (over a 24-h period) of two intraperitoneal injections (1h apart) in different combinations. The different groups and their combinations of injections were: (1) Saline (saline, saline); (2) Mel (melatonin, saline); (3) MPTP (saline, MPTP); (4) Mel-MPTP (melatonin, MPTP). Six days after the last injection, all mice were perfused transcardially with aldehyde fixative. Brains were processed for routine tyrosine hydroxylase (TH; rate limiting enzyme for dopamine production) immunochemistry and Nissl staining. Our results - using unbiased stereology - showed that there were more TH(+) (50%) and Nissl-stained (30%) cells in the SNc of the Mel-MPTP group compared to the MPTP group, indicating a clear saving or neuroprotection of these cells. In fact, we found no significant difference between the number of TH(+) and Nissl-stained SNc cells in the Mel-MPTP group compared to the controls, namely Saline and Mel groups. This indicated that melatonin pre-treatment potentially neuroprotected all the SNc cells from MPTP toxicity and death.

Neuroprotective effect of hydroxy safflor yellow A against cerebral ischemia-reperfusion injury in rats: putative role of mPTP.

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Ramagiri, Sruthi; Taliyan, Rajeev

2016-01-01

Hydroxy safflor yellow A (HSYA) has been translated clinically for cardiovascular diseases. HSYA is also greatly acknowledged for its protective effects against cerebral ischemic-reperfusion (I/R) injury. Although the precise mechanism of cerebral I/R injury is not fully understood, oxygen-derived free radicals and mitochondrial permeability transition pore (mPTP) opening during I/R injury are widely recognized as an important contributor to neuronal injury. Thus, we speculated that the neuroprotective effects of HSYA against cerebral I/R injury may be associated with mPTP modulation. Induction of I/R injury was achieved by 60 min of middle cerebral artery occlusion, followed by reperfusion for 24 h. For behavior and cognitive assessment, neurological scoring (NSS), rotarod, and Y-maze task were performed. Oxidative damage was measured in terms of markers such as malondialdehyde, reduced glutathione, and catalase levels and cerebral infarct volumes were quantified using 2,3,5-triphenyl tetrazolinium chloride staining. I/R injury-induced inflammation was determined using tumor necrosis factor-α (TNF-α) levels. Animals exposed to I/R injury showed neurological severity, functional and cognitive disability, elevated oxidative markers, and TNF-α levels along with large infarct volumes. HSYA treatment during onset of reperfusion ameliorated performance in NSS, rotarod and Y-maze attenuated oxidative damage, TNF-α levels, and infarction rate. However, treatment with carboxyatractyloside, an mPTP opener, 20 min before HSYA, attenuated the protective effect of HSYA. Our study confirmed that protective effect of HSYA may be conferred through its free radical scavenger action followed by inhibiting the opening of mPTP during reperfusion and HSYA might act as a promising therapeutic agent against cerebral I/R injury.

Mesenchymal stem cell transplantation attenuates blood brain barrier damage and neuroinflammation and protects dopaminergic neurons against MPTP toxicity in the substantia nigra in a model of Parkinson's disease.

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Chao, Yin Xia; He, Bei Ping; Tay, Samuel Sam Wah

2009-11-30

Immunomodulatory effects of transplanted mesenchymal stem cells (MSCs) in the treatment of Parkinson's disease were studied in the MPTP-induced mouse model. MPTP treatment induced a significant loss of dopaminergic neurons, decreased expressions of claudin 1, claudin 5 and occludin in the substantia nigra compacta (SNc), and functional damage of the blood brain barrier (BBB). Our study further discovered that infiltration of MBLs into the brain to bind with microglia was detected in the SNc of MPTP-treated mice, suggesting that the BBB compromise and MBL infiltration might be involved in the pathogenesis of MPTP-induced PD. In addition, MPTP treatment also increased the expression of mannose-binding lectins (MBLs) in the liver tissue. Intravenous transplantation of MSCs into MPTP-treated mice led to recovery of BBB integrity, suppression of MBL infiltration at SNc and MBL expression in the liver, suppression of microglial activation and prevention of dopaminergic neuron death. No transplanted MSCs were observed to differentiate into dopaminergic neurons, while the MSCs migrated into the SNc and released TGF-beta1 there. Therefore, intravenous transplantation of MSCs which protect dopaminergic neurons from MPTP toxicity may be engaged in anyone or a combination of these mechanisms: repair of the BBB, reduction of MBL in the brain, inhibition of microglial cytotoxicity, and direct protection of dopaminergic neurons.

Mitochondrial permeability transition pore (MPTP) desensitization increases sea urchin spermatozoa fertilization rate.

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Torrezan-Nitao, Elis; Boni, Raianna; Marques-Santos, Luis Fernando

2016-10-01

Mitochondrial permeability transition pore (MPTP) is a protein complex whose opening promotes an abrupt increase in mitochondrial inner membrane permeability. Calcium signaling pathways are described in gametes and are involved in the fertilization process. Although mitochondria may act as Ca(2+) store and have a fast calcium-releasing mechanism through MPTP, its contribution to fertilization remains unclear. The work aimed to investigate the MPTP phenomenon in sea urchin spermatozoa and its role on the fertilization. Several pharmacological tools were used to evaluate the MPTP's physiology. Our results demonstrated that MPTP occurs in male gametes in a Ca(2+) - and voltage-dependent manner and it is sensitive to cyclosporine A. Additionally, our data show that MPTP opening does not alter ROS generation in sperm cells. Inhibition of MPTP in spermatozoa strongly improved the fertilization rate, which may involve mechanisms that increase the spermatozoa lifespan. The present work is the first report of the presence of a voltage- and Ca(2+) -dependent MPTP in gametes of invertebrates and indicates MPTP opening as another evolutionary feature shared by sea urchins and mammals. Studies about MPTP in sea urchin male gametes may contribute to the elucidation of several mechanisms involved in sperm infertility. © 2016 International Federation for Cell Biology.

Effect of catalpol on senile plaques and spatial learning and memory ability in amyloid-β protein precursor/presenilin 1 double transgenic mice

Institute of Scientific and Technical Information of China (English)

宋冲

2013-01-01

Objective To investigate whether catalpol affects senile plaque formation and spatial learning and memory ability in the amyloid-βprotein precursor/presenilin 1(APP/PS1)double transgenic mice.Methods

Role of Inflammation in MPTP-Induced Dopaminergic Neuronal Death

Science.gov (United States)

2008-12-01

of MPTP to MPP+ and MPP+ entry into dopaminergic neurons are key to the neurotoxic effects of MPTP and interference in any of these processes...presented at the Society for Neuroscience Meetings in 2006 Figure 1. Tempol Structure 29 Figure 2. Tempol protects dopaminergic neurons...in PD. Dopaminergic neurons in the SNpc were protected to a significant degree against the damaging effects of MPTP by M40401 whereas its isoforms

Mechanism of toxicity of MPTP: A cause of Parkinsonism in human beings

International Nuclear Information System (INIS)

Denton, T.L.

1988-01-01

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was found in 1983 to cause a syndrome virtually identical to Parkinson's Disease in humans and other primates. The symptoms, as in idiopathic Parkinson's syndrome, are due to destruction of dopaminergic neurons in the pars compacta of the substantia nigra resulting in depletion of dopamine in the basal ganglia. The mechanism of toxicity was investigated with a dopamine containing cell line, PC12, a MPTP resistant variant (MPTP r ), and synaptosomes from the striate cortex of mice, rats, guinea pigs and a monkey. The mechanism of acute effects was studied with membrane preparations from human and rat striate cortex. MPTP displaced [ 3 H]haloperidol from binding sites in human and rat striate cortex, but could not displace [ 3 H]flupenthixol, suggesting that MPTP is a D2 receptor ligand of equivalent potency in both species. MPTP was a competitive inhibitor of uptake of [ 3 H]dopamine in PC12 but did not accumulate in PC12 or in synaptosomes of rat, guinea pig, mouse or monkey striate cortex. 100 uM MPTP depleted catecholamine levels in PC12 cells by about 50%, without killing

Elevated expression of glutathione peroxidase in PC12 cells results in protection against methamphetamine but not MPTP toxicity.

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Hom, D G; Jiang, D; Hong, E J; Mo, J Q; Andersen, J K

1997-06-01

In vivo administration of either 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or methamphetamine (MA) produces damage to the dopaminergic nervous system which may be due in part to the generation of reactive oxygen species (ROS). The resistance of superoxide dismutase (SOD) over-expressing transgenic mice to the effects of both MPTP and MA suggests the involvement of superoxide in the resulting neurotoxicity of both compounds. Superoxide can be converted by SOD to hydrogen peroxide, which itself can cause cellular degeneration by reacting with free iron to produce highly reactive hydroxyl radicals resulting in damage to proteins, nucleic acids and membrane phospholipids. Hydrogen peroxide has also been reported to be produced via inhibition of NADH dehydrogenase by MPP + formed during oxidation of MPTP by MAO-B and by dopamine auto-oxidation following MA-induced dopamine release from synaptic vesicles within nerve terminals. To test whether hydrogen peroxide is an important factor in the toxicity of either of these two neurotoxins, we created clonal PC12 lines expressing elevated levels of the hydrogen peroxide-reducing enzyme glutathione peroxidase (GSHPx). Elevation of GSHPx levels in PC12 was found to diminish the rise in ROS levels and lipid peroxidation resulting from MA but not MPTP treatment. Elevated levels of GSHPx also appeared to prevent decreases in transport-mediated dopamine uptake produced via MA administration as well as to attenuate toxin-induced cell loss as measured by either MTT reduction or LDH release. Our data, therefore, suggest that hydrogen peroxide production likely contributes to MA toxicity in dopaminergic neurons.

Antioxidant-Rich Fraction of Urtica dioica Mediated Rescue of Striatal Mito-Oxidative Damage in MPTP-Induced Behavioral, Cellular, and Neurochemical Alterations in Rats.

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Bisht, Rohit; Joshi, Bhuwan Chandra; Kalia, Ajudhiya Nath; Prakash, Atish

2017-09-01

Parkinson's disease (PD) having a complex and multi-factorial neuropathology includes mainly the degeneration of the dopaminergic nigrostriatal pathway, which is a cumulative effect of depleted endogenous antioxidant enzymes, increased oxidative DNA damage, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. The present study was designed to investigate the neuroprotective effect of a potent antioxidant from Urtica dioica in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. MPTP was administered intranigrally for the induction of PD in male Wistar rats. Behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and different biochemical, cellular, and neurochemical parameters were measured. Intranigrally repeated administration of MPTP showed significant impairment of motor co-ordination and marked increase of mito-oxidative damage and neuroinflammation in rats. Intranigral MPTP significantly decreases the dopamine and its metabolites with impairment of dopaminergic cell density in rat brain. However, post-treatment with the potent antioxidant fraction of Urtica dioica Linn. (UD) (20, 40, 80 mg/kg) improved the motor function, mito-oxidative defense alteration significantly and dose dependently in MPTP-treated rats. In addition, the potent antioxidant fraction of UD attenuated the pro-inflammatory cytokines (TNF-α and IL-β) and restored the level of dopamine and its metabolites in MPTP-induced PD in rats. Moreover, minocycline (30 mg/kg) with lower dose of UD (20 mg/kg) had significantly potentiated the protective effect of minocycline as compared to its effect with other individual drug-treated groups. In conclusion, Urtica dioica protected the dopaminergic neurons probably by reducing mito-oxidative damage, neuroinflammation, and cellular alteration along with enhanced neurotrophic potential. The above results revealed that the antioxidant rich

Resveratrol attenuates oxidative stress and improves behaviour in 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) challenged mice.

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Anandhan, Annadurai; Tamilselvam, Kuppusamy; Vijayraja, Dhanraj; Ashokkumar, Nataraj; Rajasankar, Srinivasagam; Manivasagam, Thamilarasan

2010-07-01

Parkinson's disease (PD) is the most common neurodegenerative disorder, characterized by loss of dopaminergic neurons in substantia nigra and depletion of dopamine in striatum due to mitochondrial dysfunction, oxidative stress, excitotoxicity, apoptosis, inflammation and proteasome failure. The present study deals with the neuroprotective effect of resveratrol, a wine polyphenol (50 mg/kg body weight) against MPTP (30mg/kg body weight as i.p. administration) induced mice model of idiopathic Parkinson's disease. A combination of behaviour tasks and biochemical parameters were tested using standard molecular tools. Pretreatment of resveratrol significantly reversed toxic effects of MPTP by increasing the levels of dopamine, its metabolites, GSH and activities of GPx and reducing levels of TBARS, catalase and SOD activities along with enhanced behavior performance. The multifactorial etiology of these diseases suggests that drugs with multiple targets such as resveratrol could have therapeutic potential for these pathologies.

Neuroprotection by caffeine in the MPTP model of parkinson's disease and its dependence on adenosine A2A receptors.

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Xu, K; Di Luca, D G; Orrú, M; Xu, Y; Chen, J-F; Schwarzschild, M A

2016-05-13

Considerable epidemiological and laboratory data have suggested that caffeine, a nonselective adenosine receptor antagonist, may protect against the underlying neurodegeneration of parkinson's disease (PD). Although both caffeine and more specific antagonists of the A2A subtype of adenosine receptor (A2AR) have been found to confer protection in animal models of PD, the dependence of caffeine's neuroprotective effects on the A2AR is not known. To definitively determine its A2AR dependence, the effect of caffeine on 1-methyl-4-phenyl-1,2,3,6 tetra-hydropyridine (MPTP) neurotoxicity was compared in wild-type (WT) and A2AR gene global knockout (A2A KO) mice, as well as in central nervous system (CNS) cell type-specific (conditional) A2AR knockout (cKO) mice that lack the receptor either in postnatal forebrain neurons or in astrocytes. In WT and in heterozygous A2AR KO mice caffeine pretreatment (25mg/kgip) significantly attenuated MPTP-induced depletion of striatal dopamine. By contrast in homozygous A2AR global KO mice caffeine had no effect on MPTP toxicity. In forebrain neuron A2AR cKO mice, caffeine lost its locomotor stimulant effect, whereas its neuroprotective effect was mostly preserved. In astrocytic A2AR cKO mice, both caffeine's locomotor stimulant and protective properties were undiminished. Taken together, these results indicate that neuroprotection by caffeine in the MPTP model of PD relies on the A2AR, although the specific cellular localization of these receptors remains to be determined. Copyright © 2016 IBRO. All rights reserved.

Effect of inhibition of fatty acid amide hydrolase on MPTP-induced dopaminergic neuronal damage.

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Viveros-Paredes, J M; Gonzalez-Castañeda, R E; Escalante-Castañeda, A; Tejeda-Martínez, A R; Castañeda-Achutiguí, F; Flores-Soto, M E

2017-01-16

Parkinson's disease (PD) is a neurodegenerative disorder characterised by balance problems, muscle rigidity, and slow movement due to low dopamine levels and loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The endocannabinoid system is known to modulate the nigrostriatal pathway through endogenous ligands such as anandamide (AEA), which is hydrolysed by fatty acid amide hydrolase (FAAH). The purpose of this study was to increase AEA levels using FAAH inhibitor URB597 to evaluate the modulatory effect of AEA on dopaminergic neuronal death induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our study included 4 experimental groups (n = 6 mice per group): a control group receiving no treatment, a group receiving URB597 (0.2mg/kg) every 3 days for 30 days, a group treated with MPTP (30mg/kg) for 5 days, and a group receiving URB597 and subsequently MPTP injections. Three days after the last dose, we conducted a series of behavioural tests (beam test, pole test, and stride length test) to compare motor coordination between groups. We subsequently analysed immunoreactivity of dopaminergic cells and microglia in the SNpc and striatum. Mice treated with URB597 plus MPTP were found to perform better on behavioural tests than mice receiving MPTP only. According to the immunohistochemistry study, mice receiving MPTP showed fewer dopaminergic cells and fibres in the SNpc and striatum. Animals treated with URB597 plus MPTP displayed increased tyrosine hydroxylase immunoreactivity compared to those treated with MPTP only. Regarding microglial immunoreactivity, the group receiving MPTP showed higher Iba1 immunoreactivity in the striatum and SNpc than did the group treated with URB597 plus MPTP. Our results show that URB597 exerts a protective effect since it inhibits dopaminergic neuronal death, decreases microglial immunoreactivity, and improves MPTP-induced motor alterations. Copyright © 2016 Sociedad Española de Neurología. Publicado

Mecanismo de acción antiinflamatoria de 5-O-desmetilnobiletina y derivados del catalpol en hipersensibilidad retardada.

OpenAIRE

Bas Infante, Esperanza

2007-01-01

RESUMEN La presente Tesis Doctoral se ha centrado en el estudio de 5-O-desmetilnobiletina (DMN), aislado de Sideritis tragoricanum sp. mugronensis, y los iridoides derivados del catalpol denominados escrovalentinósido (SV) y escropoliósido A (SC), aislados de Scrophularia auriculata sp. valentina. La selección de estos tres principios se basó en los estudios previos realizados en los cuales se demostraron las propiedades en modelos experimentales de inflamación aguda. Como métodos exper...

Neuroprotective effects of agmatine in mice infused with a single intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

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Matheus, Filipe C; Aguiar, Aderbal S; Castro, Adalberto A; Villarinho, Jardel G; Ferreira, Juliano; Figueiredo, Cláudia P; Walz, Roger; Santos, Adair R S; Tasca, Carla I; Prediger, Rui D S

2012-12-01

We have recently demonstrated that rodents treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suffered impairments in olfactory, cognitive, emotional and motor functions associated with time-dependent disruption of dopaminergic neurotransmission in different brain structures conceivably analogous to those observed during different stages of Parkinson's disease (PD). Agmatine, an endogenous arginine metabolite, has been proposed as a novel neuromodulator that plays protective roles in several models of neuronal cellular damage. In the present study we demonstrated that repeated treatment with agmatine (30 mg/kg, i.p.) during 5 consecutive days increased the survival rate (from 40% to 80%) of 15-month-old C57BL/6 female mice infused with a single intranasal (i.n.) administration of MPTP (1 mg/nostril), improving the general neurological status of the surviving animals. Moreover, pretreatment with agmatine was found to attenuate short-term social memory and locomotor activity impairments observed at different periods after i.n. MPTP administration. These behavioral benefits of exogenous agmatine administration were accompanied by a protection against the MPTP-induced decrease of hippocampal glutamate uptake and loss of dopaminergic neurons in the substantia nigra pars compacta of aging mice, without altering brain monoamine oxidase B (MAO-B) activity. These results provide new insights in experimental models of PD, indicating that agmatine represents a potential therapeutic tool for the management of cognitive and motor symptoms of PD, together with its neuroprotective effects. Copyright © 2012 Elsevier B.V. All rights reserved.

MPTP-induced executive dysfunction is associated with altered prefrontal serotonergic function.

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Maiti, Panchanan; Gregg, Laura C; McDonald, Michael P

2016-02-01

In Parkinson's disease, cognitive deficits manifest as fronto-striatally-mediated executive dysfunction, with impaired attention, planning, judgment, and impulse control. We examined changes in executive function in mice lesioned with subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a 3-choice serial reaction-time (SRT) task, which included measures of sustained attention and impulse control. Each trial of the baseline SRT task comprised a pseudo-random pre-cue period ranging from 3 to 8 s, followed by a 1-s cue duration. MPTP impaired all measures of impulsive behavior acutely, but with additional training their performance normalized to saline control levels. When challenged with shorter cue durations, MPTP-lesioned mice had significantly slower reaction times than wild-type mice. When challenged with longer pre-cue times, the MPTP-lesioned mice exhibited a loss of impulse control at the longer durations. In lesioned mice, striatal dopamine was depleted by 54% and the number of tyrosine-hydroxylase-positive neurons in the substantia nigra pars compacta was reduced by 75%. Serotonin (5-HT) was unchanged in the striatum and prefrontal cortex (PFC), but the ratio of 5-hydroxyindolacetic acid (5-HIAA) to 5-HT was significantly reduced in the MPTP group in the PFC. In lesioned mice, prefrontal 5-HIAA/5-HT was significantly correlated with the executive impairments and striatal norepinephrine was associated with slower reaction times. None of the neurochemical measures was significantly associated with behavior in saline-treated controls. Taken together, these results show that prefrontal 5-HT turnover may play a pivotal role in MPTP-induced executive dysfunction. Copyright © 2015 Elsevier B.V. All rights reserved.

The Effects of Melatonin with Memantin on MPTP-Induced Parkinson Model in Male Mice

Directory of Open Access Journals (Sweden)

Reza Talebi

2015-09-01

Full Text Available Abstract Background: Oxidative stress and severe neuro-excitation have significant effects on pathogenesis of Parkinson’s disease and agents with antioxidant property can potentially prevent these effects. Herein we examined potential protective effects of melatonin as an antioxidant agent and memantine as an uncompetitive receptor of NMDA, on a model of Parkinson’s disease induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP. Materials and Methods: Male mice were divided into 8 groups with 7 mice in each group: saline, ethanol, melatonin, memantin, MPTP, melatonin+MPTP, memantin+ MPTP, melatonin+ memantin+ MPTP. All of agents were injected intraperitoneally once a day for 14 days before beam traversal test. Dopaminergic neurons of the Substantia Nigra Pars compacta (SNPC were determined by immunohistochemical and were counted. Results: Melatonin improved notably movement dysfunction resulted of MPTP such as the number of errors, paces and the time of movement during behavioral test and also the counting of neurons of Substantia Nigra Pars Compacta. Memantin had a synergic effect on the most of improvements. However, the level of improvement and retrieval of signs was not as in saline and ethanol groups. Conclusion: Melatonin especially together with memantine is able to prevent some of the MPTP-induced dysfunctions. However, the protective effects were not enogh, probably because of the amount of dose and the time of injection.

In Vivo Evidence of Increased nNOS Activity in Acute MPTP Neurotoxicity: A Functional Pharmacological MRI Study

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Tiing Yee Siow

2013-01-01

Full Text Available 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP is a neurotoxin commonly used to produce an animal model of Parkinson’s disease. Previous studies have suggested a critical role for neuronal nitric oxide (NO synthase- (nNOS- derived NO in the pathogenesis of MPTP. However, NO activity is difficult to assess in vivo due to its extremely short biological half-life, and so in vivo evidence of NO involvement in MPTP neurotoxicity remains scarce. In the present study, we utilized flow-sensitive alternating inversion recovery sequences, in vivo localized proton magnetic resonance spectroscopy, and diffusion-weighted imaging to, respectively, assess the hemodynamics, metabolism, and cytotoxicity induced by MPTP. The role of NO in MPTP toxicity was clarified further by administering a selective nNOS inhibitor, 7-nitroindazole (7-NI, intraperitoneally to some of the experimental animals prior to MPTP challenge. The transient increase in cerebral blood flow (CBF in the cortex and striatum induced by systemic injection of MPTP was completely prevented by pretreatment with 7-NI. We provide the first in vivo evidence of increased nNOS activity in acute MPTP-induced neurotoxicity. Although the observed CBF change may be independent of the toxicogenesis of MPTP, this transient hyperperfusion state may serve as an early indicator of neuroinflammation.

CYP 2E1 mutant mice are resistant to DDC-induced enhancement of MPTP toxicity.

Science.gov (United States)

Viaggi, C; Vaglini, F; Pardini, C; Sgadò, P; Caramelli, A; Corsini, G U

2007-01-01

In order to reach a deeper insight into the mechanism of diethyldithiocarbamate (DDC)-induced enhancement of MPTP toxicity in mice, we showed that CYP450 (2E1) inhibitors, such as diallyl sulfide (DAS) or phenylethylisothiocyanate (PIC), also potentiate the selective DA neuron degeneration in C57/bl mice. Furthermore we showed that CYP 2E1 is present in the brain and in the basal ganglia of mice (Vaglini et al., 2004). However, because DAS and PIC are not selective CYP 2E1 inhibitors and in order to provide direct evidence for CYP 2E1 involvement in the enhancement of MPTP toxicity, CYP 2E1 knockout mice (GONZ) and wild type animals (SVI) of the same genetic background were treated with MPTP or the combined DDC + MPTP treatment. In CYP 2E1 knockout mice, DDC pretreatment completely fails to enhance MPTP toxicity, although enhancement of MPTP toxicity was regularly present in the SVI control animals. The immunohistochemical study confirms our results and suggests that CYP 2E1 may have a detoxifying role.

A beam-walking apparatus to assess behavioural impairments in MPTP-treated mice: pharmacological validation with R-(-)-deprenyl.

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Quinn, Leann P; Perren, Marion J; Brackenborough, Kim T; Woodhams, Peter L; Vidgeon-Hart, Martin; Chapman, Helen; Pangalos, Menelas N; Upton, Neil; Virley, David J

2007-08-15

A beam-walking apparatus has been evaluated for its ability to detect motor impairments in mice acutely treated with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg, s.c., single or double administration). Mice subjected to MPTP lesioning showed deficits in motor performance on the beam-walking task, for up to 6 days post-MPTP administration, as compared to saline-treated controls. In addition, MPTP-treated mice were detected to have a marked depletion in striatal dopamine levels and a concomitant reduction in substantia nigra (SN) tyrosine hydroxylase (TH) immunoreactivity, at 7 days post-MPTP administration, indicative of dopaminergic neuronal loss. Pre-administration of the potent MAO-B inhibitor R-(-)-deprenyl at 3 or 10 mg/kg, 30 min, s.c, significantly inhibited the MPTP-induced reduction in SN TH-immunoreactivity, striatal dopamine depletions and impairments in mouse motor function. The data described in the present study provides further evidence that functional deficits following an acute MPTP dosing schedule in mice can be quantified and are related to nigro-striatal dopamine function.

Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy

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Zhu, Liang [East Hospital, Tongji University School of Medicine, Shanghai (China); Dong, Chuanming [East Hospital, Tongji University School of Medicine, Shanghai (China); Department of Anatomy and Neurobiology, The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong (China); Sun, Chenxi; Ma, Rongjie; Yang, Danjing [East Hospital, Tongji University School of Medicine, Shanghai (China); Zhu, Hongwen, E-mail: hongwen_zhu@hotmail.com [Tianjin Hospital, Tianjin Academy of Integrative Medicine, Tianjin (China); Xu, Jun, E-mail: xunymc2000@yahoo.com [East Hospital, Tongji University School of Medicine, Shanghai (China)

2015-08-21

Aging of neural stem cell, which can affect brain homeostasis, may be caused by many cellular mechanisms. Autophagy dysfunction was found in aged and neurodegenerative brains. However, little is known about the relationship between autophagy and human neural stem cell (hNSC) aging. The present study used 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to treat neural precursor cells (NPCs) derived from human embryonic stem cell (hESC) line H9 and investigate related molecular mechanisms involved in this process. MPTP-treated NPCs were found to undergo premature senescence [determined by increased senescence-associated-β-galactosidase (SA-β-gal) activity, elevated intracellular reactive oxygen species level, and decreased proliferation] and were associated with impaired autophagy. Additionally, the cellular senescence phenotypes were manifested at the molecular level by a significant increase in p21 and p53 expression, a decrease in SOD2 expression, and a decrease in expression of some key autophagy-related genes such as Atg5, Atg7, Atg12, and Beclin 1. Furthermore, we found that the senescence-like phenotype of MPTP-treated hNPCs was rejuvenated through treatment with a well-known autophagy enhancer rapamycin, which was blocked by suppression of essential autophagy gene Beclin 1. Taken together, these findings reveal the critical role of autophagy in the process of hNSC aging, and this process can be reversed by activating autophagy. - Highlights: • We successfully establish hESC-derived neural precursor cells. • MPTP treatment induced senescence-like state in hESC-derived NPCs. • MPTP treatment induced impaired autophagy of hESC-derived NPCs. • MPTP-induced hESC-derived NPC senescence was rejuvenated by activating autophagy.

The Effects of Piroxicam in the Attenuation of MPP+/MPTP Toxicity In Vitro and In Vivo

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Soliman, Y.; Jackson, T.; Mazzio, E.

2010-01-01

Several lines of evidence support the neuroprotective action of cyclooxygenase-2 (COX-2) inhibitors in various models of Parkinson's disease (PD). In the current study, we investigated the neuroprotective properties of several COX inhibitors against 1-methyl-4-phenylpyridinium (MPP+) in neuroblastoma Neuro 2A (N-2A) cells in vitro and the protection against degeneration of substantia nigra pars compacta (SNc) dopaminergic (DA) neurons after the administration of 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) in C57/BL6 male mice. The data obtained demonstrate a lack of protective effects observed by COX 1-2 inhibitors ibuprofen and acetylsalicylic acid against MPP+ toxicity in N-2A, where piroxicam was protective in a dose dependent manner (MPP+ control: 15 ± 2% MPP+ piroxicam: 5 mM 89 ± 4%). The data also indicate a drop in mitochondrial oxygen (O2) consumption and ATP during MPP+ toxicity with no restoration of mitochondrial function concurrent to a heightened concentration of somatic ATP during piroxicam rescue. These findings indicate that the neuroprotective effects of COX inhibitors against MPP+ are not consistent, but that piroxicam may work through an unique mechanism to propel anaerobic energy metabolism. On the other hand, using mice, piroxicam (20 mg/kg) was effective against MPTP-induced dopaminergic degeneration in the (SNc) and loss of locomotive function in mice. Administering a 3 day pre-treatment of piroxicam (20 mg/kg) was effective in antagonizing the losses in SNc tyrosine hydroxylase protein expression, SNc DA concentration and associated anomaly in ambulatory locomotor activity. It was concluded from these findings that piroxicam is unique among COX inhibitors in providing very significant neuroprotection against MPP+ in vitro and in vivo. PMID:18612814

[Effect of Shouwu Shudi Yin on dopaminegic neurons in MPTP induced Parkinson's disease mouse model].

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Tunje, Reginachizi; Ye, Yang-Lie; Sonauddin, Ahmed; Hansraj, Bhugun; Ngawang, Sangye; Shivani, Sharma; Zhang, Xiong; Zhu, Jian-Hong; Liu, Rong-Pei

2016-09-01

In order to investigate the effect of Shouwu Shudi Yin on dopaminegic neurons in MPTP induced Parkinson's disease mouse model and the possible mechamism, the experimental mice were randomly divided into 4 groups: control, Shouwu Shudi Yin, MPTP and the treatment (MPTP+Shouwu Shudi Yin) groups. The number of tyrosine hydroxylase (TH) positive cells in the substantia nigra was measured by immunohistochemistry, and mRNA expression of TH and glutathione peroxidase (GPX) were detected by PCR. The results showed that the number of TH positive cells and mRNA expression of TH were significantly reduced in MPTP group compared with the control (PYin didn't show protective effect. Compared to MPTP group, the mRNA expression of four subtypes of GPX were increased in various degrees in the treatment group pretreated with Shouwu Shudi Yin, although the difference was not statistically significant. These indicated that the preventive medication of Shouwu Shudi Yin don't have protective effect on the mice with Parkinson' s disease induced by MPTP, but it may enhance the antioxidant capacity through increasing the expression of GPX. Copyright© by the Chinese Pharmaceutical Association.

Resveratrol attenuates oxidative stress and improves behaviour in 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) challenged mice

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Anandhan, Annadurai; Tamilselvam, Kuppusamy; Vijayraja, Dhanraj; Ashokkumar, Nataraj; Rajasankar, Srinivasagam; Manivasagam, Thamilarasan

2010-01-01

Background Parkinson's disease (PD) is the most common neurodegenerative disorder, characterized by loss of dopaminergic neurons in substantia nigra and depletion of dopamine in striatum due to mitochondrial dysfunction, oxidative stress, excitotoxicity, apoptosis, inflammation and proteasome failure. Purpose The present study deals with the neuroprotective effect of resveratrol, a wine polyphenol (50 mg/kg body weight) against MPTP (30mg/kg body weight as i.p. administration) induced mice mo...

Effects of (-)-sesamin on motor and memory deficits in an MPTP-lesioned mouse model of Parkinson's disease treated with l-DOPA.

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Zhao, T T; Shin, K S; Kim, K S; Park, H J; Kim, H J; Lee, K E; Lee, M K

2016-12-17

The present study investigated the effects of (-)-sesamin on motor and memory deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD) with l-3,4-dihydroxyphenylalanine (l-DOPA). MPTP-lesioned (30mg/kg/day, 5days) mice showed deficits in memory including habit learning memory and spatial memory, which were further aggravated by daily treatment with 25mg/kg l-DOPA for 21days. However, daily treatment with (-)-sesamin (25 and 50mg/kg) for 21days ameliorated memory deficits in an MPTP-lesioned mouse model of PD treated with l-DOPA (25mg/kg). Both (-)-sesamin doses reduced decreases in the retention latency time in the passive avoidance test, latency to fall of rotarod test and distance traveled in the open field test, and attenuated decreases in tyrosine hydroxylase (TH)-immunopositive cells, dopamine, and its metabolites in the substantia nigra-striatum. (-)-Sesamin reduced increases in the retention transfer latency time in the elevated plus-maze test and N-methyl-d-aspartate receptor (NMDAR) expression and reduced decreases in the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB) in the hippocampus. In contrast, daily treatment with 10mg/kg l-DOPA for 21days ameliorated memory deficits in MPTP-lesioned mice, and this effect was further improved by treatment with (-)-sesamin (25 and 50mg/kg). These results suggest that (-)-sesamin protects against habit learning memory deficits by activating the dopamine neuronal system, while spatial memory deficits are decreased by its modulatory effects on the NMDAR-ERK1/2-CREB system. Accordingly, (-)-sesamin may act as an adjuvant phytonutrient for motor and memory deficits in patients with PD receiving l-DOPA. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Intranasal mucoadhesivemicroemulsion for neuroprotective effect of curcuminin mptp induced Parkinson model

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Snigdha Das Mandal

2017-06-01

Full Text Available ABSTRACT This study was to investigate the neuroprotective effect of curcumin against inflammation-mediated dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mice model of Parkinson's disease (PD. Curcumin loaded sodium hyaluronate based mucoadhesive microemulsion (CMME was developed by using Box Behnken design of Response surface method (RSM and was characterized. Male C57BL/6 mice were first treated with four intraperitoneal injections of MPTP (20 mg/kg of body weight at 2 h intervals followed CMME intranasal administration for 14 days at 2.86 mg of curcumin/kg of body weight per once a day. Optimal CMME containing 3% Capmul MCM as oil phase, 37 % of Accenon CC and Transcutol HP at 2.5:1 ratio and 0.5% sodium hyaluronate was stable, non-ciliotoxic with 57.66 nm±3.46 as average globule size. PdI value (0.190 ± 0.19 and TEM result depicted the narrow size distribution of CMME.All three independent variables had a significant effect (p<0.05 on the responses and the designed model was significant for all taken responses. In-vivo results revealed significant reduction of MPTP-mediated dopamine depletion after nasal administration of CMME. MPTP intoxication significantly decreased striatal DA content to 21.29 % which was then elevated to 55.37% after intranasal curcumin treatment. Significant improvement in motor performance as well as gross behavioural activity of mice was observed from rota-rod and open field test findings. Findings of the investigation revealed the symptomatic neuroprotection of curcumin against MPTP-induced neurodegradation in the striatum and hence could be considered as a promising approach to treat PD.

ASIC1a Deficient Mice Show Unaltered Neurodegeneration in the Subacute MPTP Model of Parkinson Disease.

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Daniel Komnig

Full Text Available Inflammation contributes to the death of dopaminergic neurons in Parkinson disease and can be accompanied by acidification of extracellular pH, which may activate acid-sensing ion channels (ASIC. Accordingly, amiloride, a non-selective inhibitor of ASIC, was protective in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mouse model of Parkinson disease. To complement these findings we determined MPTP toxicity in mice deficient for ASIC1a, the most common ASIC isoform in neurons. MPTP was applied i.p. in doses of 30 mg per kg on five consecutive days. We determined the number of dopaminergic neurons in the substantia nigra, assayed by stereological counting 14 days after the last MPTP injection, the number of Nissl positive neurons in the substantia nigra, and the concentration of catecholamines in the striatum. There was no difference between ASIC1a-deficient mice and wildtype controls. We are therefore not able to confirm that ASIC1a are involved in MPTP toxicity. The difference might relate to the subacute MPTP model we used, which more closely resembles the pathogenesis of Parkinson disease, or to further targets of amiloride.

Regulation of the Bcas1 and Baiap3 transcripts in the subthalamic nucleus in mice recovering from MPTP toxicity

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Lauridsen, J B; Johansen, J L; Rekling, J C

2011-01-01

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure leads to significant and irreversible damage to dopaminergic neurons in both mice and humans. While MPTP exposure in humans causes permanent symptoms of Parkinson's disease, MPTP treated mice will recover behaviorally over a 3-week period....... This mouse specific recovery might be linked to transcriptional changes in the basal ganglia enabling mice to maintain normal motor function in spite of low striatal dopamine levels. Laser microdissection was used to isolate the subthalamic nucleus from mice 7 and 28 days following MPTP exposure. High...

Geldanamycin induces heat shock protein 70 and protects against MPTP-induced dopaminergic neurotoxicity in mice.

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Shen, Hai-Ying; He, Jin-Cai; Wang, Yumei; Huang, Qing-Yuan; Chen, Jiang-Fan

2005-12-02

As key molecular chaperone proteins, heat shock proteins (HSPs) represent an important cellular protective mechanism against neuronal cell death in various models of neurological disorders. In this study, we investigated the effect as well as the molecular mechanism of geldanamycin (GA), an inhibitor of Hsp90, on 1-methyl-4-pheny-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity, a mouse model of Parkinson disease. Neurochemical analysis showed that pretreatment with GA (via intracerebral ventricular injection 24 h prior to MPTP treatment) increased residual dopamine content and tyrosine hydroxylase immunoreactivity in the striatum 24 h after MPTP treatment. To dissect out the molecular mechanism underlying this neuroprotection, we showed that the GA-mediated protection against MPTP was associated with a reduction of cytosolic Hsp90 and an increase in Hsp70, with no significant changes in Hsp40 and Hsp25 levels. Furthermore, in parallel with the induction of Hsp70, striatal nuclear HSF1 levels and HSF1 binding to heat shock element sites in the Hsp70 promoter were significantly enhanced by the GA pretreatment. Together these results suggested that the molecular cascade leading to the induction of Hsp70 is critical to the neuroprotection afforded by GA against MPTP-induced neurotoxicity in the brain and that pharmacological inhibition of Hsp90 may represent a potential therapeutic strategy for Parkinson disease.

GSTpi expression in MPTP-induced dopaminergic neurodegeneration of C57BL/6 mouse midbrain and striatum.

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Castro-Caldas, Margarida; Neves Carvalho, Andreia; Peixeiro, Isabel; Rodrigues, Elsa; Lechner, Maria Celeste; Gama, Maria João

2009-06-01

MPTP-induced dopaminergic neurotoxicity involves major biochemical processes such as oxidative stress and impaired energy metabolism, leading to a significant reduction in the number of nigrostriatal dopaminergic neurons. Glutathione S-transferase pi (GSTpi) is a phase II detoxifying enzyme that provides protection of cells from injury by toxic chemicals and products of oxidative stress. In humans, polymorphisms of GSTP1 affect substrate selectivity and stability increasing the susceptibility to parkinsonism-inducing effects of environmental toxins. Given the ability of MPTP to increase the levels of reactive oxygen species and the link between altered redox potential and the expression and activity of GSTpi, we investigated the effect of MPTP on GSTpi cellular concentration in an in vivo model of Parkinson's disease. The present study demonstrates that GSTpi is actively expressed in both substantia nigra pars compacta and striatum of C57BL/6 mice brain, mostly in oligodendrocytes and astrocytes. After systemic administration of MPTP, GSTpi expression is significantly increased in glial cells in the vicinity of dopaminergic neurons cell bodies and fibers. The results suggest that GSTpi expression may be part of the mechanism underlying the ability of glial cells to elicit protection against the mechanisms involved in MPTP-induced neuronal death.

Activin A Inhibits MPTP and LPS-Induced Increases in Inflammatory Cell Populations and Loss of Dopamine Neurons in the Mouse Midbrain In Vivo.

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Stayte, Sandy; Rentsch, Peggy; Tröscher, Anna R; Bamberger, Maximilian; Li, Kong M; Vissel, Bryce

2017-01-01

Parkinson's disease is a chronic neurodegenerative disease characterized by a significant loss of dopaminergic neurons within the substantia nigra pars compacta region and a subsequent loss of dopamine within the striatum. A promising avenue of research has been the administration of growth factors to promote the survival of remaining midbrain neurons, although the mechanism by which they provide neuroprotection is not understood. Activin A, a member of the transforming growth factor β superfamily, has been shown to be a potent anti-inflammatory following acute brain injury and has been demonstrated to play a role in the neuroprotection of midbrain neurons against MPP+-induced degeneration in vitro. We hypothesized that activin A may offer similar anti-inflammatory and neuroprotective effects in in vivo mouse models of Parkinson's disease. We found that activin A significantly attenuated the inflammatory response induced by both MPTP and intranigral administration of lipopolysaccharide in C57BL/6 mice. We found that administration of activin A promoted survival of dopaminergic and total neuron populations in the pars compacta region both 8 days and 8 weeks after MPTP-induced degeneration. Surprisingly, no corresponding protection of striatal dopamine levels was found. Furthermore, activin A failed to protect against loss of striatal dopamine transporter expression in the striatum, suggesting the neuroprotective action of activin A may be localized to the substantia nigra. Together, these results provide the first evidence that activin A exerts potent neuroprotection and anti-inflammatory effects in the MPTP and lipopolysaccharide mouse models of Parkinson's disease.

Methamphetamine protects against MPTP neurotoxicity in C57BL mice.

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Sziráki, I; Kardos, V; Patthy, M; Pátfalusi, M; Budai, G

1994-01-14

Methamphetamine (5 mg/kg) administered 30 min prior to each injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (3 x 30 mg/kg, at 24 h intervals) prevents the reduction of striatal levels of dopamine and its metabolites in C57BL mice. Methamphetamine and amphetamine inhibit the uptake of 1-methyl-4-phenylpyridinium (MPP+) by striatal synaptosomes of rats. A 30-min post-treatment with methamphetamine or amphetamine also prevents the MPTP-induced dopamine depletion, suggesting that their protective effect is related to the blockade of MPP+ uptake into dopaminergic neurons. Since amphetamine and methamphetamine are themselves neurotoxins at higher doses, this work demonstrated the protection against the actions of one neurotoxin by the administration of another.

Effects of gypenosides on anxiety disorders in MPTP-lesioned mouse model of Parkinson's disease.

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Shin, Keon Sung; Zhao, Ting Ting; Choi, Hyun Sook; Hwang, Bang Yeon; Lee, Chong Kil; Lee, Myung Koo

2014-06-03

Ethanol extract (GP-EX) of Gynostemma pentaphyllum (GP) ameliorates chronic stress-induced anxiety in mice. The present study investigated the effects of gypenoside-enriched components (GPS), GP-EX and water extract of GP (GP-WX) on MPTP lesion-induced affective disorders in C57BL/6 mice. GPS (50mg/kg) and GP-EX (50mg/kg) for 21 day-treatment period improved the symptom of anxiety disorders in the MPTP-lesioned mouse model of PD with or without L-DOPA treatment, which was examined by the elevated plus-maze and marble burying tests. In these states, treatments with GPS (50mg/kg) and GP-EX (50mg/kg) significantly increased the brain levels of dopamine and serotonin in the MPTP-lesioned mouse model of PD with or without l-DOPA treatment. In addition, treatments with GPS (50mg/kg) and GP-EX (50mg/kg) showed protective effects on dopaminergic neurons in MPTP-lesioned mouse model of PD with or without L-DOPA treatment. In contrast, GPS (30 mg/kg) and GP-WX (50mg/kg) showed anxiolytic effects in the same animal models, but it was not significant. These results suggest that GPS (50mg/kg) and GP-EX (50mg/kg) showed anxiolytic effects on affective disorders and protective effects on dopaminergic neurons by modulating the brain levels of dopamine and serotonin in the MPTP-lesioned mouse model of PD with or without l-DOPA treatment. Clinical trials of GPS and GP-EX need to be conducted further so as to develop adjuvant therapeutic agents for PD patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Role of Nitric Oxide in MPTP-Induced Dopaminergic Neuron Degeneration

National Research Council Canada - National Science Library

Przedborski, Serge

2002-01-01

...) induced dopaminergic (DA) neuron death in this mouse model of Parkinson's Disease (PD). Our previous work demonstrated that the superoxide radical is involved in the MPTP neurotoxic process in SNpc DA neurons...

Real-Time Fluorescence Measurements of ROS and [Ca2+] in Ischemic / Reperfused Rat Hearts: Detectable Increases Occur only after Mitochondrial Pore Opening and Are Attenuated by Ischemic Preconditioning.

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Tatyana Andrienko

Full Text Available Mitochondrial permeability transition pore (mPTP opening is critical for ischemia / reperfusion (I/R injury and is associated with increased [Ca2+] and reactive oxygen species (ROS. Here we employ surface fluorescence to establish the temporal sequence of these events in beating perfused hearts subject to global I/R. A bespoke fluorimeter was used to synchronously monitor surface fluorescence and reflectance of Langendorff-perfused rat hearts at multiple wavelengths, with simultaneous measurements of hemodynamic function. Potential interference by motion artefacts and internal filtering was assessed and minimised. Re-oxidation of NAD(PH and flavoproteins on reperfusion (detected using autofluorescence was rapid (t0.5 < 15 s and significantly slower following ischemic preconditioning (IP. This argues against superoxide production from reduced Complex 1 being a critical mediator of initial mPTP opening during early reperfusion. Furthermore, MitoPY1 (a mitochondria-targeted H2O2-sensitive fluorescent probe and aconitase activity measurements failed to detect matrix ROS increases during early reperfusion. However, two different fluorescent cytosolic ROS probes did detect ROS increases after 2-3 min of reperfusion, which was shown to be after initiation of mPTP opening. Cyclosporin A (CsA and IP attenuated these responses and reduced infarct size. [Ca2+]i (monitored with Indo-1 increased progressively during ischemia, but dropped rapidly within 90 s of reperfusion when total mitochondrial [Ca2+] was shown to be increased. These early changes in [Ca2+] were not attenuated by IP, but substantial [Ca2+] increases were observed after 2-3 min reperfusion and these were prevented by both IP and CsA. Our data suggest that the major increases in ROS and [Ca2+] detected later in reperfusion are secondary to mPTP opening. If earlier IP-sensitive changes occur that might trigger initial mPTP opening they are below our limit of detection. Rather, we suggest that

Real-Time Fluorescence Measurements of ROS and [Ca2+] in Ischemic / Reperfused Rat Hearts: Detectable Increases Occur only after Mitochondrial Pore Opening and Are Attenuated by Ischemic Preconditioning.

Science.gov (United States)

Andrienko, Tatyana; Pasdois, Philippe; Rossbach, Andreas; Halestrap, Andrew P

2016-01-01

Mitochondrial permeability transition pore (mPTP) opening is critical for ischemia / reperfusion (I/R) injury and is associated with increased [Ca2+] and reactive oxygen species (ROS). Here we employ surface fluorescence to establish the temporal sequence of these events in beating perfused hearts subject to global I/R. A bespoke fluorimeter was used to synchronously monitor surface fluorescence and reflectance of Langendorff-perfused rat hearts at multiple wavelengths, with simultaneous measurements of hemodynamic function. Potential interference by motion artefacts and internal filtering was assessed and minimised. Re-oxidation of NAD(P)H and flavoproteins on reperfusion (detected using autofluorescence) was rapid (t0.5 ROS increases during early reperfusion. However, two different fluorescent cytosolic ROS probes did detect ROS increases after 2-3 min of reperfusion, which was shown to be after initiation of mPTP opening. Cyclosporin A (CsA) and IP attenuated these responses and reduced infarct size. [Ca2+]i (monitored with Indo-1) increased progressively during ischemia, but dropped rapidly within 90 s of reperfusion when total mitochondrial [Ca2+] was shown to be increased. These early changes in [Ca2+] were not attenuated by IP, but substantial [Ca2+] increases were observed after 2-3 min reperfusion and these were prevented by both IP and CsA. Our data suggest that the major increases in ROS and [Ca2+] detected later in reperfusion are secondary to mPTP opening. If earlier IP-sensitive changes occur that might trigger initial mPTP opening they are below our limit of detection. Rather, we suggest that IP may inhibit initial mPTP opening by alternative mechanisms such as prevention of hexokinase 2 dissociation from mitochondria during ischemia.

Exercise does not protect against MPTP-induced neurotoxicity in BDNF haploinsufficient mice.

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Kim M Gerecke

Full Text Available Exercise has been demonstrated to potently protect substantia nigra pars compacta (SN dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-induced neurotoxicity. One mechanism proposed to account for this neuroprotection is the upregulation of neurotrophic factors. Several neurotrophic factors, including Brain Derived Neurotrophic Factor (BDNF, have been shown to upregulate in response to exercise. In order to determine if exercise-induced neuroprotection is dependent upon BDNF, we compared the neuroprotective effects of voluntary exercise in mice heterozygous for the BDNF gene (BDNF+/- with strain-matched wild-type (WT mice. Stereological estimates of SNpc DA neurons from WT mice allowed 90 days exercise via unrestricted running demonstrated complete protection against the MPTP-induced neurotoxicity. However, BDNF+/- mice allowed 90 days of unrestricted exercise were not protected from MPTP-induced SNpc DA neuron loss. Proteomic analysis comparing SN and striatum from 90 day exercised WT and BDNF+/- mice showed differential expression of proteins related to energy regulation, intracellular signaling and trafficking. These results suggest that a full genetic complement of BDNF is critical for the exercise-induced neuroprotection of SNpc DA neurons.

Olfaction in three genetic and two MPTP-induced Parkinson's disease mouse models.

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Stefan Kurtenbach

Full Text Available Various genetic or toxin-induced mouse models are frequently used for investigation of early PD pathology. Although olfactory impairment is known to precede motor symptoms by years, it is not known whether it is caused by impairments in the brain, the olfactory epithelium, or both. In this study, we investigated the olfactory function in three genetic Parkinson's disease (PD mouse models and mice treated with MPTP intraperitoneally and intranasally. To investigate olfactory function, we performed electro-olfactogram recordings (EOGs and an olfactory behavior test (cookie-finding test. We show that neither a parkin knockout mouse strain, nor intraperitoneal MPTP treated animals display any olfactory impairment in EOG recordings and the applied behavior test. We also found no difference in the responses of the olfactory epithelium to odorants in a mouse strain over-expressing doubly mutated α-synuclein, while this mouse strain was not suitable to test olfaction in a cookie-finding test as it displays a mobility impairment. A transgenic mouse expressing mutated α-synuclein in dopaminergic neurons performed equal to control animals in the cookie-finding test. Further we show that intranasal MPTP application can cause functional damage of the olfactory epithelium.

Autoradiography of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): Uptake in the monoaminergic pathways and in melanin containing tissues

Energy Technology Data Exchange (ETDEWEB)

Lyden, A; Lindquist, N G; Bondesson, U; Larsson, B S; Olsson, L -I

1985-01-01

A recently discovered neurotoxic compound, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, has been found to cause a parkinsonian-like syndrome in man and monkey, but not in laboratory animals such as rat, mouse and guinea pig. MPTP seems to selectively destroy the melanin containing dopaminergic cells in pars compacta of substantia nigra. Lower mammalian species do not have melanin in these cells, which indicates that the presence of neuromelanin may be of importance for the development of MPTP-induced lesions. By means of whole-body autoradiography of TH-MPTP in mice, accumulation and retention was observed in the dopaminergic pathways, in locus ceruleus and in structures in the medulla oblongata and spinal cord. A high uptake was also seen in melanin-containing tissues such as in the eyes of pigmented mice. MPTP has earlier been found to have high affinity in vitro for dopamine melanin, which is similar to the pigment in substantia nigra. The typical features of the MPTP-induced neurotoxicity with destruction of pigmented nerve cells and development of parkinsonism may be due to accumulation adn retention of MPTP and its metabolites in these cells. In species with pigmented nerve cells, such as man and monkey, the accumulation may be much more pronounced because of the melanin affinity of MPTP and its metabolites. (author).

Parkinson's disease: Studies on the pathology of the disease and the mechanism of action of the neurotoxin MPTP

International Nuclear Information System (INIS)

D'Amato, R.J.

1988-01-01

In humans and animals, exposure to 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) causes certain clinical, pathological, and neurochemical features of Parkinson's disease (PD). MPTP is metabolized in the brain by monoamine oxidase (MAOb) to 1-methyl-4-phenylpyridine (MPP + ), which is selectively accumulated and concentrated by high affinity uptake mechanisms into catecholamine neurons. We have demonstrated high affinity binding of MPP + to neuromelanin which may result in a toxic intraneuronal sequestration of MPP + . The involvement of neuromelanin is further supported by the demonstration that monkeys pretreated with chloroquine prior to the administration of MPTP are protected from MPTP induced neurotoxicity. Decreases in serotonin levels have been reported in the brains and spinal fluid of patients with both Parkinson's and Alzheimer's disease. In an effort to investigate the pathology of serotonin neurons in postmortem brain tissue from Parkinson's and Alzheimer's patients, [ 3 H]citalopram was characterized as a means of labeling serotonin uptake sites present on serotonin terminals

Amentoflavone protects dopaminergic neurons in MPTP-induced Parkinson's disease model mice through PI3K/Akt and ERK signaling pathways

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Cao, Qin; Qin, Liyue; Huang, Fei; Wang, Xiaoshuang; Yang, Liu; Shi, Hailian; Wu, Hui; Zhang, Beibei; Chen, Ziyu; Wu, Xiaojun

2017-01-01

Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc). Mitochondrial dysfunction and cell apoptosis are suggested to be actively involved in the pathogenesis of PD. In the present study, the neuroprotective effect of amentoflavone (AF), a naturally occurring biflavonoid from Selaginella tamariscina, was examined in PD models both in vitro and in vivo. On SH-SY5Y cells, AF treatment dose-dependently reduced 1-methyl-4-phenylpyridinium (MPP + )-induced nuclear condensation and loss of cell viability without obvious cytotoxicity. It inhibited the activation of caspase-3 and p21 but increased the Bcl-2/Bax ratio. Further study disclosed that AF enhanced the phosphorylation of PI3K, Akt and ERK1/2 down-regulated by MPP + in SH-SY5Y cells, the effect of which could be blocked by LY294002, the inhibitor of PI3K. Consistently, AF alleviated the behavioral deterioration in pole and traction tests and rescued the loss of dopaminergic neurons in SNpc and fibers in striatum in methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mice. It also could enhance the activation of PI3K and Akt as well as Bcl-2/Bax ratio in SN. Moreover, AF alleviated gliosis as well as the gene expression levels of IL-1β and iNOS in SN. Collectively, these results suggested that AF protected dopaminergic neurons against MPTP/MPP + -induced neurotoxicity, which might be mediated through activation of PI3K/Akt and ERK signaling pathways in dopaminergic neurons and attenuation of neuroinflammation. - Highlights: • AF protected dopaminergic neurons against MPTP/MPP + -induced neurotoxicity. • AF modulated PI3K/Akt and ERK signaling pathways. • AF could alleviate neuroinflammation in SN.

Amentoflavone protects dopaminergic neurons in MPTP-induced Parkinson's disease model mice through PI3K/Akt and ERK signaling pathways

Energy Technology Data Exchange (ETDEWEB)

Cao, Qin; Qin, Liyue; Huang, Fei, E-mail: Fei_H@hotmail.com; Wang, Xiaoshuang; Yang, Liu; Shi, Hailian; Wu, Hui; Zhang, Beibei; Chen, Ziyu; Wu, Xiaojun, E-mail: xiaojunwu320@126.com

2017-03-15

Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc). Mitochondrial dysfunction and cell apoptosis are suggested to be actively involved in the pathogenesis of PD. In the present study, the neuroprotective effect of amentoflavone (AF), a naturally occurring biflavonoid from Selaginella tamariscina, was examined in PD models both in vitro and in vivo. On SH-SY5Y cells, AF treatment dose-dependently reduced 1-methyl-4-phenylpyridinium (MPP{sup +})-induced nuclear condensation and loss of cell viability without obvious cytotoxicity. It inhibited the activation of caspase-3 and p21 but increased the Bcl-2/Bax ratio. Further study disclosed that AF enhanced the phosphorylation of PI3K, Akt and ERK1/2 down-regulated by MPP{sup +} in SH-SY5Y cells, the effect of which could be blocked by LY294002, the inhibitor of PI3K. Consistently, AF alleviated the behavioral deterioration in pole and traction tests and rescued the loss of dopaminergic neurons in SNpc and fibers in striatum in methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mice. It also could enhance the activation of PI3K and Akt as well as Bcl-2/Bax ratio in SN. Moreover, AF alleviated gliosis as well as the gene expression levels of IL-1β and iNOS in SN. Collectively, these results suggested that AF protected dopaminergic neurons against MPTP/MPP{sup +}-induced neurotoxicity, which might be mediated through activation of PI3K/Akt and ERK signaling pathways in dopaminergic neurons and attenuation of neuroinflammation. - Highlights: • AF protected dopaminergic neurons against MPTP/MPP{sup +}-induced neurotoxicity. • AF modulated PI3K/Akt and ERK signaling pathways. • AF could alleviate neuroinflammation in SN.

Reduced 125I-meta-iodobenzylguanidine uptake and norepinephrine transporter density in the hearts of mice with MPTP-induced parkinsonism

International Nuclear Information System (INIS)

Fukumitsu, Nobuyoshi; Suzuki, Masahiko; Fukuda, Takahiro; Kiyono, Yasushi; Kajiyama, Satomi; Saji, Hideo

2006-01-01

Uptake of 123 I-meta-iodobenzylguanidine ( 123 I-MIBG) is markedly reduced in the hearts of patients with Parkinson's disease. Although the mechanism of this reduction is unclear, 12 5 I-MIBG uptake is similarly reduced in the hearts of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP)-induced parkinsonism. Three groups of ten 15-week-old C57BL6 mice received intraperitoneal injections of (1) saline (control) (2) 10 mg/kg MPTP or (3) 40 mg/kg MPTP. After 0.185 MBq of 125 I-MIBG was injected, the percent injected dose of 125 I-MIBG per gram of tissue (%ID/g) was determined and cardiac concentrations of norepinephrine were measured. Cardiac concentrations of norepinephrine transporter (NET) were measured in three groups of twenty 15-week-old C57BL6 mice receiving these same treatments. The %ID/g in mice receiving 10 or 40 mg/kg MPTP (5.7±1.1 and 4.4±1.2%/g) was significantly lower than that in control mice (11.3±2.2%/g; P 5 and 7.50±0.89x10 5 pg/wet g) was significantly lower than that in control mice (9.21±0.97x10 5 pg/wet g; P 125 I-MIBG and NET density decreased as the dose of MPTP increased. This study clearly shows that reduced cardiac 12 5 I-MIBG uptake in mice with MPTP-induced parkinsonism is closely related to the reduced NET density in postganglionic cardiac sympathetic nerve terminals

Striatal dopamine transporter, regional cerebral blood flow and glucose utilization in MPTP-induced parkinson disease mice model

International Nuclear Information System (INIS)

Gao Yunchao; Wu Chunying; Xiang Jingde; Lin Xiangtong; Zhu Huiqing

2005-01-01

Objective: To explore the variation of regional cerebral blood flow (rCBF), glucose utilization as well as the neurotoxic effect on dopaminergic neurons induced by neurotoxin 1-methy-4-phenyl-1,2,3,6-tetrahy-dropyridine (MPTP). Methods: Eight-week old male C57BL/6 mice were given a total dose of 0-80 mg/kg MPTP intraperitoneally. Ten days later the mice were sacrificed for tyrosine hydroxylase (TH)-immunopositive cell count- ing in substantia nigra using SP immunohistochemistry. Vivo autoradiography was employed to measure striatal do- pamine transporter (DAT) loss, rCBF and glucose utilization in striatum and thalamus. Results: The extents of DAT depletion and TH-immunopositive cell loss were positively correlated (r=0.998, P O.2), while glucose utilization was only slightly reduced in caudate/putamen and thalamus by 3.0% and 5.4% in 80 mg/kg MPTP-treated mice (P<0.05). Conclusion: Significant dose-dependent relationship was in presence of MPTP induced dopaminergic neurons loss, changes of rCBF in caudate/putamen and thalamus were not significant, while the glucose utilization was slightly decreased in higher dose group. (authors)

Astaxanthin attenuates neurotoxicity in a mouse model of Parkinson’s disease

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B. Grimmig, L. Daly

2017-08-01

Full Text Available Background: Astaxanthin (AXT is a natural carotenoid with diverse biological activities. Although it is best known as a potent antioxidant, recent work suggests additional mechanisms of action that have the potential to oppose the ongoing pathophysiology of Parkinson’s disease (PD. For example, AXT has a putative role in modulating microglial activity and preserving mitochondrial function, thereby implicating this compound as a neuroprotective agent. Both oxidative stress and inflammation are involved in the progression of many neurodegenerative diseases. Therefore, we examined the efficacy for AXT to reduced neurotoxicity in a toxic model of PD in mice. Methods: In this study, we used a 4-week dietary supplementation of algae derived AXT to reduce 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP induced dopaminergic cell death. Results: AXT treated mice were protected against the loss of tyrosine hydroxylase (TH staining in the substantia nigra (SN after MPTP exposure compared to the control diet. This effect of preserved TH immunoreactivity was also observed in the striatum. Furthermore, AXT administration was able to interrupt the neuroinflammatory process known to contribute to neurodegeneration in this model. Conclusions: We demonstrate that AXT neuroprotection was associated with attenuated microglial activation as indicated by reduced immunohistochemical detection of IBA-1 in the SN and striatum of AXT treated mice. Altogether, these studies suggest that AXT has neuroprotective property in the central nervous system against MPTP neurodegeneration.

Ethanol stem bark extract of Rauwolfia vomitoria ameliorates MPTP ...

African Journals Online (AJOL)

Methods: The Parkinson's disease was induced in rats by a single intraperitoneal (IP) injection of MPTP. After 72h of induction, the young adult male rats were treated with oral administration of stem bark ethanol extract of the plant daily for 2 weeks. The blood chemistry, antioxidant markers and brain dopamine levels were ...

Neuroprotective effects of an oxyntomodulin analogue in the MPTP mouse model of Parkinson's disease.

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Liu, WeiZhen; Li, Yanwei; Jalewa, Jaishree; Saunders-Wood, Taylor; Li, Lin; Hölscher, Christian

2015-10-15

Oxyntomodulin is a hormone and a growth factor. It activates two receptors, the Glucagon-like peptide 1 (GLP-1) and the glucagon receptor. GLP-1 mimetics are on the market as treatments for type 2 diabetes and are well tolerated. These drugs have shown neuroprotective properties in animal models of neurodegenerative disorders. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in animal models of Parkinson's disease (PD), and a clinical trial in PD patients showed promising first positive results. D-Ser2-oxyntomodulin (Oxy) is a protease resistant oxyntomodulin analogue that has been developed to treat diabetes. Here we demonstrate for the first time that such analogues have neuroprotective effects. The drug showed protective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected daily (20 mg/kg i.p.) for 7 days, and Oxy injected once-daily for 14 days i.p. Oxy treatment prevented or reversed the MPTP- induced motor impairment (Rotarod, spontaneous locomotion, swim activity, muscle strength test), the MPTP-induced reduction in Tyrosine Hydroxylase (TH) levels (dopamine synthesis) in the substantia nigra and basal ganglia, the reduction of the synaptic marker synapstophysin, the inactivation of the growth factor kinase Akt/PKB and of the anti-apoptotic signaling molecule Bcl-2, and the increase of levels of the pro-inflammatory cytokine TNF-α. The results demonstrate that oxyntomodulin analogues show promise as a novel treatment of PD. Copyright © 2015 Elsevier B.V. All rights reserved.

A novel biomechanical analysis of gait changes in the MPTP mouse model of Parkinson’s disease

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Werner J. Geldenhuys

2015-08-01

Full Text Available Parkinson’s disease (PD is an age-associated neurodegenerative disorder hallmarked by a loss of mesencephalic dopaminergic neurons. Accurate recapitulation of the PD movement phenotype in animal models of the disease is critical for understanding disease etiology and developing novel therapeutic treatments. However, most existing behavioral assays currently applied to such animal models fail to adequately detect and subsequently quantify the subtle changes associated with the progressive stages of PD. In this study, we used a video-based analysis system to develop and validate a novel protocol for tracking locomotor performance in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mouse model of PD. We anticipated that (1 treated mice should use slower, shorter, and less frequent strides and (2 that gait deficits should monotonically increase following MPTP administration, as the effects of neurodegeneration become manifest. Video-based biomechanical analyses, utilizing behavioral measures motivated by the comparative biomechanics literature, were used to quantify gait dynamics over a seven-day period following MPTP treatment. Analyses revealed shuffling behaviors consistent with the gait symptoms of advanced PD in humans. Here we also document dramatic gender-based differences in locomotor performance during the progression of the MPTP-induced lesion, despite male and female mice showing similar losses of striatal dopaminergic cells following MPTP administration. Whereas female mice appeared to be protected against gait deficits, males showed multiple changes in gait kinematics, consistent with the loss of locomotor agility and stability. Overall, these data show that the novel video analysis protocol presented here is a robust method capable of detecting subtle changes in gait biomechanics in a mouse model of PD. Our findings indicate that this method is a useful means by which to easily and economically screen preclinical therapeutic

Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid.

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Teixeira, José; Oliveira, Catarina; Cagide, Fernando; Amorim, Ricardo; Garrido, Jorge; Borges, Fernanda; Oliveira, Paulo J

2018-12-01

Pharmacological interventions targeting mitochondria present several barriers for a complete efficacy. Therefore, a new mitochondriotropic antioxidant (AntiOxBEN 3 ) based on the dietary antioxidant gallic acid was developed. AntiOxBEN 3 accumulated several thousand-fold inside isolated rat liver mitochondria, without causing disruption of the oxidative phosphorylation apparatus, as seen by the unchanged respiratory control ratio, phosphorylation efficiency, and transmembrane electric potential. AntiOxBEN 3 showed also limited toxicity on human hepatocarcinoma cells. Moreover, AntiOxBEN 3 presented robust iron-chelation and antioxidant properties in both isolated liver mitochondria and cultured rat and human cell lines. Along with its low toxicity profile and high antioxidant activity, AntiOxBEN 3 strongly inhibited the calcium-dependent mitochondrial permeability transition pore (mPTP) opening. From our data, AntiOxBEN 3 can be considered as a lead compound for the development of a new class of mPTP inhibitors and be used as mPTP de-sensitiser for basic research or clinical applications or emerge as a therapeutic application in mitochondria dysfunction-related disorders.

Gynostemma pentaphyllum Ethanolic Extract Protects Against Memory Deficits in an MPTP-Lesioned Mouse Model of Parkinson's Disease Treated with L-DOPA.

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Kim, Kyung Sook; Zhao, Ting Ting; Shin, Keon Sung; Park, Hyun Jin; Cho, Yoon Jeong; Lee, Kyung Eun; Kim, Seung Hwan; Lee, Myung Koo

2017-01-01

This study investigated the effects of ethanol extract from Gynostemma pentaphyllum (GP-EX) on memory deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD) (MPTP-lesioned mice). MPTP (30 mg/kg/day, 5 days)-lesioned mice showed deficits of habit learning memory and spatial memory, which were further aggravated by treatment with L-3,4-dihydroxyphenylalanine (L-DOPA) (25 mg/kg, 21 days). However, treatment with GP-EX (50 mg/kg, 21 days) ameliorated memory deficits in MPTP-lesioned mice treated with L-DOPA (25 mg/kg): GP-EX prevented the decreases in retention latency time in the passive avoidance test and tyrosine hydroxylase-immunopositive cells and dopamine levels in the nigrostriatum. GP-EX also reduced increases in retention transfer latency time of the elevated plus-maze test and expression of N-methyl-D-aspartate (NMDA) receptor and improved decreases in phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB) in the hippocampus in the same models. By contrast, L-DOPA treatment (10 mg/kg, 21 days) ameliorated memory deficits in MPTP-lesioned mice, which were further improved by GP-EX treatment. These results suggest that GP-EX ameliorates habit learning memory deficits by activating dopaminergic neurons and spatial memory deficits by modulating NMDA receptor-ERK1/2-CREB system in MPTP-lesioned mice treated with L-DOPA. GP-EX may serve as an adjuvant phytonutrient for memory deficits in PD.

Alterations in energy metabolism, neuroprotection and visual signal transduction in the retina of Parkinsonian, MPTP-treated monkeys.

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Laura Campello

Full Text Available Parkinson disease is mainly characterized by the degeneration of dopaminergic neurons in the central nervous system, including the retina. Different interrelated molecular mechanisms underlying Parkinson disease-associated neuronal death have been put forward in the brain, including oxidative stress and mitochondrial dysfunction. Systemic injection of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP to monkeys elicits the appearance of a parkinsonian syndrome, including morphological and functional impairments in the retina. However, the intracellular events leading to derangement of dopaminergic and other retinal neurons in MPTP-treated animal models have not been so far investigated. Here we have used a comparative proteomics approach to identify proteins differentially expressed in the retina of MPTP-treated monkeys. Proteins were solubilized from the neural retinas of control and MPTP-treated animals, labelled separately with two different cyanine fluorophores and run pairwise on 2D DIGE gels. Out of >700 protein spots resolved and quantified, 36 were found to exhibit statistically significant differences in their expression levels, of at least ± 1.4-fold, in the parkinsonian monkey retina compared with controls. Most of these spots were excised from preparative 2D gels, trypsinized and subjected to MALDI-TOF MS and LC-MS/MS analyses. Data obtained were used for protein sequence database interrogation, and 15 different proteins were successfully identified, of which 13 were underexpressed and 2 overexpressed. These proteins were involved in key cellular functional pathways such as glycolysis and mitochondrial electron transport, neuronal protection against stress and survival, and phototransduction processes. These functional categories underscore that alterations in energy metabolism, neuroprotective mechanisms and signal transduction are involved in MPTP-induced neuronal degeneration in the retina, in similarity to

Non-human primate FOG develops with advanced parkinsonism induced by MPTP Treatment.

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Revuelta, Gonzalo J; Uthayathas, Subramaniam; Wahlquist, Amy E; Factor, Stewart A; Papa, Stella M

2012-10-01

Freezing of gait (FOG) is a debilitating feature of Parkinson's disease (PD) and other forms of parkinsonism. The anatomical or pathophysiological correlates are poorly understood largely due to the lack of a well-established animal model. Here we studied whether FOG is reproduced in the non-human primate (NHP) model of PD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys (Genus Macaca, n=29) were examined for the development of FOG, and the leg movements were recorded with accelerometry. The relationships between developing FOG and the animals' characteristics, the MPTP treatments, and the modeled outcomes were determined. In parkinsonian monkeys FOG developed frequently (48%) manifesting similar characteristics to those seen in PD patients. In addition, FOG episodes in the monkey were accompanied by leg trembling with the typical duration (2-10s) and frequency (~7 Hz). The development of NHP FOG was significantly associated with the severity of parkinsonism, as shown by high motor disability scores (≥ 20) and levodopa-induced dyskinesia scores (p=0.01 and p=0.04, respectively). Differences in demographics and MPTP treatments (doses, treatment duration, etc.) had no influence on NHP FOG occurrence, with the exception of gender that showed FOG predominance in males (p=0.03). The unique features of FOG in PD can be replicated in severely parkinsonian macaques, and this represents the first description of a FOG animal model. Published by Elsevier Inc.

Injury-stimulated Sonic hedgehog expression in microglia contributes to neuroinflammatory response in the MPTP model of Parkinson's disease

International Nuclear Information System (INIS)

Lee, Jeong Hwi; Chung, Young Cheul; Bok, Eugene; Lee, Hankyu; Huh, Sue Hee; Lee, Ji Eun; Jin, Byung Kwan; Ko, Hyuk Wan

2017-01-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder in which dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) region are selectively destroyed. Sonic hedgehog (Shh) has been well known to play a key role in a variety of processes such as embryogenesis, cell proliferation and protection, and tissue repair during inflammation. However, the evidences for the innate role of Shh in adult brain injury are presently lacking and studies have been needed to unveil the importance of Shh in the process of neurodegeneration. Here, we investigated the role of Shh in the pathologic progress of Parkinson's disease in MPTP-induced animal model system. Interestingly, we observed that Shh expression was gradually increased in MPTP affected SNpc region. Activated microglia exclusively expressed SHH in vivo and we could recapitulate Shh induction in activated cultured primary microglia cells. Using the SHH responsive Cre-loxP binary genetic reporter transgenic mouse system, we also found that most of the cell types except for oligodendrocyte in the SNpc region reacted to the SHH by MPTP injection. Taken together, activated microglia induced Shh expression and most neural cells except oligodendrocyte responded to microglia-derived SHH in MPTP-treated SN. These results suggest that SHH in activated microglia by MPTP-injection might be involved in the innate processes of recovery from neurotoxin induced injury in the PD animal model system. - Highlights: • Sonic hedgehog (Shh) was induced by MPTP neurotoxin at the Substantia Nigra (SN) in vivo. • Activated microglia are major cell type for SHH expression in vivo and in vitro. • Different types of cells in the brain, except oligodendrocyte, respond to microglia-derived SHH in SN region.

Early Paradoxical Increase of Dopamine: A Neurochemical Study of Olfactory Bulb in Asymptomatic and Symptomatic MPTP Treated Monkeys

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Christian Pifl

2017-05-01

Full Text Available Parkinson’s disease (PD is a neurodegenerative disease with both motor and non-motor manifestations. Hyposmia is one of the early non-motor symptoms, which can precede motor symptoms by several years. The relationship between hyposmia and PD remains elusive. Olfactory bulb (OB pathology shows an increased number of olfactory dopaminergic cells, protein aggregates and dysfunction of neurotransmitter systems. In this study we examined tissue levels of dopamine (DA and serotonin (5-hydroxytryptamine, 5-HT and their metabolites, of noradrenaline (NA and of the amino acid neurotransmitters aspartate, glutamate, taurine and γ-aminobutyric acid in OBs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP treated Macaca fascicularis in different stages, including monkeys who were always asymptomatic, monkeys who recovered from mild parkinsonian signs, and monkeys with stable moderate or severe parkinsonism. DA was increased compared to controls, while neither NA and 5-HT nor the amino acid neurotransmitters were significantly changed. Furthermore, DA increased before stable motor deficits appear with +51% in asymptomatic and +96% in recovered monkeys. Unchanged DA metabolites suggest a special metabolic profile of the newly formed DA neurons. Significant correlation of homovanillic acid (HVA with taurine single values within the four MPTP groups and of aspartate with taurine within the asymptomatic and recovered MPTP groups, but not within the controls suggest interactions in the OB between taurine and the DA system and taurine and the excitatory neurotransmitter triggered by MPTP. This first investigation of OB in various stages after MPTP administration suggests that the DA increase seems to be an early phenomenon, not requiring profound nigrostriatal neurodegeneration or PD symptoms.

5-HT2A receptor antagonists improve motor impairments in the MPTP mouse model of Parkinson's disease

OpenAIRE

Ferguson, Marcus C.; Nayyar, Tultul; Deutch, Ariel Y.; Ansah, Twum A.

2010-01-01

Clinical observations have suggested that ritanserin, a 5-HT2A/C receptor antagonist may reduce motor deficits in persons with Parkinson's Disease (PD). To better understand the potential antiparkinsonian actions of ritanserin, we compared the effects of ritanserin with the selective 5-HT2A receptor antagonist M100907 and the selective 5-HT2C receptor antagonist SB 206553 on motor impairments in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP-treated mice exhibited...

CNB-001 a Novel Curcumin Derivative, Guards Dopamine Neurons in MPTP Model of Parkinson’s Disease

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Richard L. Jayaraj

2014-01-01

Full Text Available Copious experimental and postmortem studies have shown that oxidative stress mediated degeneration of nigrostriatal dopaminergic neurons underlies Parkinson’s disease (PD pathology. CNB-001, a novel pyrazole derivative of curcumin, has recently been reported to possess various neuroprotective properties. This study was designed to investigate the neuroprotective mechanism of CNB-001 in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP rodent model of PD. Administration of MPTP (30 mg/kg for four consecutive days exacerbated oxidative stress and motor impairment and reduced tyrosine hydroxylase (TH, dopamine transporter, and vesicular monoamine transporter 2 (VMAT2 expressions. Moreover, MPTP induced ultrastructural changes such as distorted cristae and mitochondrial enlargement in substantia nigra and striatum region. Pretreatment with CNB-001 (24 mg/kg not only ameliorated behavioral anomalies but also synergistically enhanced monoamine transporter expressions and cosseted mitochondria by virtue of its antioxidant action. These findings support the neuroprotective property of CNB-001 which may have strong therapeutic potential for treatment of PD.

Analogues of desferrioxamine B designed to attenuate iron-mediated neurodegeneration: synthesis, characterisation and activity in the MPTP-mouse model of Parkinson's disease.

Science.gov (United States)

Gotsbacher, Michael P; Telfer, Thomas J; Witting, Paul K; Double, Kay L; Finkelstein, David I; Codd, Rachel

2017-07-19

Parkinson's disease (PD) is a neurodegenerative disorder characterised by the death of dopaminergic neurons in the substantia nigra pars compacta (SNpc) region of the brain and formation of α-synuclein-containing intracellular inclusions. Excess intraneuronal iron in the SNpc increases reactive oxygen species (ROS), which identifies removing iron as a possible therapeutic strategy. Desferrioxamine B (DFOB, 1) is an iron chelator produced by bacteria. Its high Fe(iii) affinity, water solubility and low chronic toxicity is useful in removing iron accumulated in plasma from patients with transfusion-dependent blood disorders. Here, lipophilic analogues of DFOB with increased potential to cross the blood-brain barrier (BBB) have been prepared by conjugating ancillary compounds onto the amine terminus. The ancillary compounds included the antioxidants rac-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (rac-trolox, rac-TLX (a truncated vitamin E variant)), R-TLX, S-TLX, methylated derivatives of 3-(6-hydroxy-2-methylchroman-2-yl)propionic acid (α-CEHC, γ-CEHC, δ-CEHC), or 4-(5-hydroxy-3-methyl-1H-pyrazol-1-yl)benzoic acid (carboxylic acid derivative of edaravone, EDA). Compounds 2-8 could have dual function in attenuating ROS by chelating Fe(iii) and via the antioxidant ancillary group. A conjugate between DFOB and an ancillary unit without antioxidant properties (3,5-dimethyladamantane-1-carboxylic acid (AdA dMe )) was included (9). Compounds 2-9 were more lipophilic (log P -0.05 to 3.39) than DFOB (log P -2.62) and showed an average plasma protein binding 6 times greater than DFOB. The ABTS˙ + radical assay indicated 2-8 had antioxidant activity ascribable to the ancillary fragment. Administration of 2 and 9 in the mouse model of PD using the neurotoxin prodrug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which recapitulates elevated iron of human PD, resulted in significant neuronal protection (p compounds for PD.

5-HT2A receptor antagonists improve motor impairments in the MPTP mouse model of Parkinson's disease.

Science.gov (United States)

Ferguson, Marcus C; Nayyar, Tultul; Deutch, Ariel Y; Ansah, Twum A

2010-01-01

Clinical observations have suggested that ritanserin, a 5-HT(2A/C) receptor antagonist may reduce motor deficits in persons with Parkinson's Disease (PD). To better understand the potential antiparkinsonian actions of ritanserin, we compared the effects of ritanserin with the selective 5-HT(2A) receptor antagonist M100907 and the selective 5-HT(2C) receptor antagonist SB 206553 on motor impairments in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP-treated mice exhibited decreased performance on the beam-walking apparatus. These motor deficits were reversed by acute treatment with L-3,4-dihydroxyphenylalanine (levodopa). Both the mixed 5-HT(2A/C) antagonist ritanserin and the selective 5-HT(2A) antagonist M100907 improved motor performance on the beam-walking apparatus. In contrast, SB 206553 was ineffective in improving the motor deficits in MPTP-treated mice. These data suggest that 5-HT(2A) receptor antagonists may represent a novel approach to ameliorate motor symptoms of Parkinson's disease. Published by Elsevier Ltd.

LncRNA NEAT1 promotes autophagy in MPTP-induced Parkinson's disease through stabilizing PINK1 protein.

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Yan, Wang; Chen, Zhao-Ying; Chen, Jia-Qi; Chen, Hui-Min

2018-02-19

Long non-coding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) was found to be closely related to the pathological changes in brain and nervous system. However, the role of NEAT1 and its potential mechanism in Parkinson's disease (PD) largely remain uncharacterized. In this study, PD mouse model was established by intraperitoneal injection of MPTP. The numbers of TH + neurons, NEAT1 expression and the level of PINK1, LC3-II, LC3-I protein were assessed in PD mice. SH-SY5Y cells were treated with MPP + as PD cell model. RNA pull-down assay was used to identify the interaction between NEAT1 and PINK1 in vitro. The endogenous expression of NEAT1 was modified by lentiviral vector carrying interference sequence for NEAT1 in vivo. The numbers of TH + neurons significantly decreased in PD mice compared with the control. The expressions of NEAT1, PINK1 protein and LC3-II/LC3-I level were increased by MPTP in vitro and in vivo. Moreover, NEAT1 positively regulated the protein level of PINK1 through inhibition of PINK1 protein degradation. And NEAT1 mediated the effects of MPP + on SH-SY5Y cells through stabilization of PINK1 protein. The results of in vivo experiments revealed that NEAT1 knockdown could effectively suppress MPTP-induced autophagy in vivo that alleviated dopaminergic neuronal injury. LncRNA NEAT1 promoted the MPTP-induced autophagy in PD through stabilization of PINK1 protein. Copyright © 2017 Elsevier Inc. All rights reserved.

Date preliminare privind unele manifestări ale durerii într-un model de șobolan MPTP-indus a bolii Parkinson

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Daniela Carmen Ababei

2015-06-01

Full Text Available Parkinson's disease (PD is less known as a disease causing pain syndromes, although pain is found in 40-80 % of PD patients, as described by the very few reports in this area of research. Moreover, in some PD patients, pain is so severe and intractable that it overshadows the motor symptoms of the disorder. Still, pain in PD frequently goes under acknowledged and undertreated. Also, the studies regarding pain perception in the existing animal models of PD are very few. We experimentally induced the PD model in rats by injecting subcutaneously one dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20mg/kg, while the control group received saline. The behavioral testing for pain included the hot-plate task and was performed 7 days after MPTP injection. In this way, our rat model resulted from the acute treatment with a low dose of MPTP, exhibited an increased sensitivity to pain perception, as demonstrated by the significant decrease in the values of the latency time in hot-plate for rats treated with MPTP, as compared to the controls. In this way, further studies in this area of research seem warranted.

Mucuna pruriens Protects against MPTP Intoxicated Neuroinflammation in Parkinson's Disease through NF-κB/pAKT Signaling Pathways.

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Rai, Sachchida N; Birla, Hareram; Singh, Saumitra S; Zahra, Walia; Patil, Ravishankar R; Jadhav, Jyoti P; Gedda, Mallikarjuna R; Singh, Surya P

2017-01-01

Till date, drugs that have been used to manage Parkinson's disease (PD) have only shown symptomatic relief with several adverse effects besides their inability to prevent neurodegeneration. Neuroinflammation plays an important role in the advancement of PD and can be targeted for its effective treatment. Researchers have suggested that herbal plants exhibiting the anti-inflammatory and anti-oxidant properties are therefore beneficial to human health. Conventionally, Mucuna pruriens (Mp) seeds are used for maintaining male virility in India. Reportedly, Mp is used as a rejuvenator drug having neuroprotective property. Our study aimed to investigate effects of aqueous extract of Mp (100 mg/kgbwt) on neuroinflammation, orally administered to mice intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as well as the molecular mechanism involved in the progression of PD. In this study, we have observed significant behavioral abnormalities beside decreased antioxidant defense in MPTP intoxicated mice. We have also observed significant increase in inflammatory parameters like Glial Fibrillary Acidic Protein, Inducible Nitric Oxide Synthase, Intercellular Cell Adhesion Molecule, and Tumor Necrosis Factor alpha in substantia nigra pars compacta (SNpc) of parkinsonian mice, while Mp treatment has notably reduced these inflammatory parameters. Mp also inhibited the MPTP induced activation of NF-κB and promoted pAkt1 activity which further prevented the apoptosis of the dopaminergic neurons. Moreover, Mp exhibited significant antioxidant defense by inhibiting the lipid peroxidation and nitrite level, and by improving catalase activity and enhancing GSH level in nigrostriatal region of mouse brain. Mp also recovered the behavioral abnormalities in MPTP treated mice. Additionally, Mp treatment considerably increased the immunoreactivity of Tyrosine Hydroxylase and Dopamine Transporter in SNpc of parkinsonian mice. Our high performance liquid chromatography

An application of a new planar positron imaging system (PPIS) in a small animal. MPTP-induced parkinsonism in mouse

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Takamatsu, Hiroyuki; Noda, Akihiro; Kakiuchi, Takeharu

2004-01-01

Recent animal PET research has led to the development of PET scanners for small animals. A planar positron imaging system (PPIS) was newly developed to study physiological function in small animals and plants in recent years. To examine the usefulness of PPIS for functional study in small animals, we examined dopaminergic images of mouse striata in MPTP-induced parkinsonism. Male C57BL/6NCrj mice were treated with MPTP 7 days before the PPIS study. Scans were performed to measure dopamine D 1 receptor binding and dopamine transporter availability with [ 11 C]SCH23390 (about 2 MBq) and [ 11 C]β-CFT (about 2 MBq), respectively. After the PPIS study, dopamine content in the striatum was measured by high-performance liquid chromatography (HPLC). The MPTP treatment significantly reduced dopamine content in the striatum 7 days after treatment. In the MPTP-treated group, [ 11 C]β-CFT binding in the striatum was significantly decreased compared with the control group, while striatal [ 11 C]SCH23390 binding was not affected. Dopamine content in the striatum was significantly correlated with the striatal binding of [ 11 C]β-CFT. The present results suggest that PPIS is able to determine brain function in a small animal. Using PPIS, high throughput imaging of small animal brain functions could be achieved. (author)

Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson's disease.

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Kadoguchi, Naoto; Okabe, Shinji; Yamamura, Yukio; Shono, Misaki; Fukano, Tatsuya; Tanabe, Akie; Yokoyama, Hironori; Kasahara, Jiro

2014-06-25

Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase dopamine release in the cortical neurons with 5-HT dependent manner. To examine whether mirtazapine has a therapeutic potency in Parkinson's disease (PD), we examined this compound in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model of PD. Male C57BL/6 mice were subjected to MPTP treatment to establish a PD model. Mirtazapine was administered once a day for 3 days after MPTP treatment. MPTP-induced motor dysfunction, assessed by beam-walking and rota-rod tests, was significantly improved by administration of mirtazapine. Biochemical examinations by high performance liquid chromatography and western blot analysis suggested mirtazapine facilitated utilization of dopamine by increasing turnover and protein expression of transporters, without affecting on neurodegenerative process by MPTP. These therapeutic effects of mirtazapine were reduced by administration of WAY100635, an inhibitor for 5HT1AR, or of clonidine, a selective agonist for α2-NAR, or of prazosin, an inhibitor for α1-NAR, respectively. Our results showed mirtazapine had a therapeutic potency against PD in a mouse model. Because PD patients sometimes show depression together, it will be a useful drug for a future PD treatment.

Patterns of Cell Activity in the Subthalamic Region Associated with the Neuroprotective Action of Near-Infrared Light Treatment in MPTP-Treated Mice

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Victoria E. Shaw

2012-01-01

Full Text Available We have shown previously that near-infrared light (NIr treatment or photobiomodulation neuroprotects dopaminergic cells in substantia nigra pars compacta (SNc from degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP in mice. The present study explores whether NIr treatment changes the patterns of Fos expression in the subthalamic region, namely, the subthalamic nucleus (STN and zona incerta (ZI; both cell groups have abnormally overactive cells in parkinsonian cases. BALB/c mice were treated with MPTP (100–250 mg/kg or saline either over 30 hours followed by either a two-hour or six-day survival period (acute model or over five weeks followed by a three-week survival period (chronic model. NIr and MPTP were applied simultaneously. Brains were processed for Fos immunochemistry, and cell number was estimated using stereology. Our major finding was that NIr treatment reduced (30–45% the increase in Fos+ cell number evident in the STN and ZI after MPTP insult. This reduction was concurrent with the neuroprotection of dopaminergic SNc cells shown previously and was evident in both MPTP models (except for the 2 hours survival period which showed no changes in cell number. In summary, our results indicated that NIr had long lasting effects on the activity of cells located deep in the brain and had repaired partially the abnormal activity generated by the parkinsonian toxin.

25-Hydroxyvitamin D depletion does not exacerbate MPTP-induced dopamine neuron damage in mice.

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E Danielle Dean

Full Text Available Recent clinical evidence supports a link between 25-hydroxyvitamin D insufficiency (serum 25-hydroxyvitamin D [25(OHD] levels <30 ng/mL and Parkinson's disease. To investigate the effect of 25(OHD depletion on neuronal susceptibility to toxic insult, we induced a state of 25(OHD deficiency in mice and then challenged them with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP. We found there was no significant difference between control and 25(OHD-deficient animals in striatal dopamine levels or dopamine transporter and tyrosine hydroxylase expression after lesioning with MPTP. Additionally, we found no difference in tyrosine hydroxylase expression in the substantia nigra pars compacta. Our data suggest that reducing 25(OHD serum levels in mice has no effect on the vulnerability of nigral dopaminergic neurons in vivo in this model system of parkinsonism.

Hericium erinaceus mycelium and its isolated erinacine A protection from MPTP-induced neurotoxicity through the ER stress, triggering an apoptosis cascade.

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Kuo, Hsing-Chun; Lu, Chien-Chang; Shen, Chien-Heng; Tung, Shui-Yi; Hsieh, Meng Chiao; Lee, Ko-Chao; Lee, Li-Ya; Chen, Chin-Chu; Teng, Chih-Chuan; Huang, Wen-Shih; Chen, Te-Chuan; Lee, Kam-Fai

2016-03-18

Hericium erinaceus is an edible mushroom; its various pharmacological effects which have been investigated. This study aimed to demonstrate whether efficacy of oral administration of H. erinaceus mycelium (HEM) and its isolated diterpenoid derivative, erinacine A, can act as an anti-neuroinflammatory agent to bring about neuroprotection using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson's disease, which results in motor disturbances, in addition to elucidating the mechanisms involved. Mice were treated with and without HEM or erinacine A, after MPTP injection for brain injuries by the degeneration of dopaminergic nigrostriatal neurons. The efficacy of oral administration of HEM improved MPTP-induced loss of tyrosine hydroxylase positive neurons and brain impairment in the substantia nigra pars compacta as measured by brain histological examination. Treatment with HEM reduced MPTP-induced dopaminergic cell loss, apoptotic cell death induced by oxidative stress, as well as the level of glutathione, nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE). Furthermore, HEM reversed MPTP-associated motor deficits, as revealed by the analysis of rotarod assessment. Our results demonstrated that erinacine A decreases the impairment of MPP-induced neuronal cell cytotoxicity and apoptosis, which were accompanied by ER stress-sustained activation of the IRE1α/TRAF2, JNK1/2 and p38 MAPK pathways, the expression of C/EBP homologous protein (CHOP), IKB-β and NF-κB, as well as Fas and Bax. These physiological and brain histological changes provide HEM neuron-protective insights into the progression of Parkinson's disease, and this protective effect seems to exist both in vivo and in vitro.

Mucuna pruriens Protects against MPTP Intoxicated Neuroinflammation in Parkinson’s Disease through NF-κB/pAKT Signaling Pathways

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Sachchida N. Rai

2017-12-01

Full Text Available Till date, drugs that have been used to manage Parkinson’s disease (PD have only shown symptomatic relief with several adverse effects besides their inability to prevent neurodegeneration. Neuroinflammation plays an important role in the advancement of PD and can be targeted for its effective treatment. Researchers have suggested that herbal plants exhibiting the anti-inflammatory and anti-oxidant properties are therefore beneficial to human health. Conventionally, Mucuna pruriens (Mp seeds are used for maintaining male virility in India. Reportedly, Mp is used as a rejuvenator drug having neuroprotective property. Our study aimed to investigate effects of aqueous extract of Mp (100 mg/kgbwt on neuroinflammation, orally administered to mice intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP as well as the molecular mechanism involved in the progression of PD. In this study, we have observed significant behavioral abnormalities beside decreased antioxidant defense in MPTP intoxicated mice. We have also observed significant increase in inflammatory parameters like Glial Fibrillary Acidic Protein, Inducible Nitric Oxide Synthase, Intercellular Cell Adhesion Molecule, and Tumor Necrosis Factor alpha in substantia nigra pars compacta (SNpc of parkinsonian mice, while Mp treatment has notably reduced these inflammatory parameters. Mp also inhibited the MPTP induced activation of NF-κB and promoted pAkt1 activity which further prevented the apoptosis of the dopaminergic neurons. Moreover, Mp exhibited significant antioxidant defense by inhibiting the lipid peroxidation and nitrite level, and by improving catalase activity and enhancing GSH level in nigrostriatal region of mouse brain. Mp also recovered the behavioral abnormalities in MPTP treated mice. Additionally, Mp treatment considerably increased the immunoreactivity of Tyrosine Hydroxylase and Dopamine Transporter in SNpc of parkinsonian mice. Our high performance liquid

Mucuna pruriens Protects against MPTP Intoxicated Neuroinflammation in Parkinson’s Disease through NF-κB/pAKT Signaling Pathways

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Rai, Sachchida N.; Birla, Hareram; Singh, Saumitra S.; Zahra, Walia; Patil, Ravishankar R.; Jadhav, Jyoti P.; Gedda, Mallikarjuna R.; Singh, Surya P.

2017-01-01

Till date, drugs that have been used to manage Parkinson’s disease (PD) have only shown symptomatic relief with several adverse effects besides their inability to prevent neurodegeneration. Neuroinflammation plays an important role in the advancement of PD and can be targeted for its effective treatment. Researchers have suggested that herbal plants exhibiting the anti-inflammatory and anti-oxidant properties are therefore beneficial to human health. Conventionally, Mucuna pruriens (Mp) seeds are used for maintaining male virility in India. Reportedly, Mp is used as a rejuvenator drug having neuroprotective property. Our study aimed to investigate effects of aqueous extract of Mp (100 mg/kgbwt) on neuroinflammation, orally administered to mice intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as well as the molecular mechanism involved in the progression of PD. In this study, we have observed significant behavioral abnormalities beside decreased antioxidant defense in MPTP intoxicated mice. We have also observed significant increase in inflammatory parameters like Glial Fibrillary Acidic Protein, Inducible Nitric Oxide Synthase, Intercellular Cell Adhesion Molecule, and Tumor Necrosis Factor alpha in substantia nigra pars compacta (SNpc) of parkinsonian mice, while Mp treatment has notably reduced these inflammatory parameters. Mp also inhibited the MPTP induced activation of NF-κB and promoted pAkt1 activity which further prevented the apoptosis of the dopaminergic neurons. Moreover, Mp exhibited significant antioxidant defense by inhibiting the lipid peroxidation and nitrite level, and by improving catalase activity and enhancing GSH level in nigrostriatal region of mouse brain. Mp also recovered the behavioral abnormalities in MPTP treated mice. Additionally, Mp treatment considerably increased the immunoreactivity of Tyrosine Hydroxylase and Dopamine Transporter in SNpc of parkinsonian mice. Our high performance liquid chromatography

Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson’s disease

Science.gov (United States)

2014-01-01

Background Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase dopamine release in the cortical neurons with 5-HT dependent manner. To examine whether mirtazapine has a therapeutic potency in Parkinson’s disease (PD), we examined this compound in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model of PD. Results Male C57BL/6 mice were subjected to MPTP treatment to establish a PD model. Mirtazapine was administered once a day for 3 days after MPTP treatment. MPTP-induced motor dysfunction, assessed by beam-walking and rota-rod tests, was significantly improved by administration of mirtazapine. Biochemical examinations by high performance liquid chromatography and western blot analysis suggested mirtazapine facilitated utilization of dopamine by increasing turnover and protein expression of transporters, without affecting on neurodegenerative process by MPTP. These therapeutic effects of mirtazapine were reduced by administration of WAY100635, an inhibitor for 5HT1AR, or of clonidine, a selective agonist for α2-NAR, or of prazosin, an inhibitor for α1-NAR, respectively. Conclusion Our results showed mirtazapine had a therapeutic potency against PD in a mouse model. Because PD patients sometimes show depression together, it will be a useful drug for a future PD treatment. PMID:24965042

A novel dual GLP-1 and GIP receptor agonist is neuroprotective in the MPTP mouse model of Parkinson's disease by increasing expression of BNDF.

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Ji, Chenhui; Xue, Guo-Fang; Lijun, Cao; Feng, Peng; Li, Dongfang; Li, Lin; Li, Guanglai; Hölscher, Christian

2016-03-01

The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors with neuroprotective properties. GLP-1 mimetics are on the market as treatments for type 2 diabetes and are well tolerated. Both GLP-1 and GIP mimetics have shown neuroprotective properties in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. Novel GLP-1/GIP dual-agonist peptides have been developed and are tested in diabetic patients. Here we demonstrate the neuroprotective effects of a novel dual agonist (DA-JC1) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once-daily (20 mg/kg i.p.) for 7 days, and the dual agonist was injected 30 min later i.p. (50 nmol/kg bw). The PI3k inhibitor LY294002 (0.6 mg/kg i.v.) was co-injected in one group. DA-JC1 reduced or reversed most of the MPTP induced motor impairments in the rotarod and in a muscle strength test. The number of tyrosine hydroxylase (TH) positive neurons in the substantia nigra (SN) was reduced by MPTP and increased by DA-JC1. The ratio of anti-inflammatory Bcl-2 to pro-inflammatory BAX as well as the activation of the growth factor kinase Akt was reduced by MPTP and reversed by DA-JC1. The PI3k inhibitor had only limited effect on the DA-JC1 drug effect. Importantly, levels of the neuroprotective brain derived neurotropic factor (BDNF) were reduced by MPTP and enhanced by DA-JC1. The results demonstrate that DA-JC1 shows promise as a novel treatment for PD. Copyright © 2016. Published by Elsevier B.V.

Protective effects of a polysaccharide from Spirulina platensis on dopaminergic neurons in an MPTP-induced Parkinson′s disease model in C57BL/6J mice

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Fang Zhang

2015-01-01

Full Text Available The present study aimed to determine whether a polysaccharide obtained from Spirulina platensis shows protective effects on dopaminergic neurons. A Parkinson′s disease model was established through the intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP in C57BL/6J mice. Prior to the MPTP injection, some mice were pretreated with intraperitoneal injections of a polysaccharide derived from Spirulina platensis once daily for 10 days. The results showed that the immunoreactive staining and mRNA expression of the dopamine transporter and tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, in the substantia nigra, were significantly increased in mice pretreated with 800 mg/kg of the polysaccharide compared with those in MPTP-treated mice. The activities of superoxide dismutase and glutathione peroxidase in the serum and midbrain were also increased significantly in mice injected with MPTP after pretreatment with the polysaccharide from Spirulina platensis. By contrast, the activity of monoamine oxidase B in serum and midbrain maintained unchanged. These experimental findings indicate that the polysaccharide obtained from Spirulina platensis plays a protective role against the MPTP-induced loss of dopaminergic neurons in C57BL/6J mice, and that the antioxidative properties of this polysaccharide likely underlie its neuroprotective effect.

Neuroprotective Effects of Salidroside in the MPTP Mouse Model of Parkinson’s Disease: Involvement of the PI3K/Akt/GSK3β Pathway

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Wei Zhang

2016-01-01

Full Text Available The degenerative loss through apoptosis of dopaminergic neurons in the substantia nigra pars compacta plays a primary role in the progression of Parkinson’s disease (PD. Our in vitro experiments suggested that salidroside (Sal could protect against 1-methyl-4-phenylpyridine-induced cell apoptosis in part by regulating the PI3K/Akt/GSK3β pathway. The current study aims to increase our understanding of the protective mechanisms of Sal in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine- (MPTP- induced PD mouse model. We found that pretreatment with Sal could protect against MPTP-induced increase of the time of turning downwards and climbing down to the floor. Sal also prevented MPTP-induced decrease of locomotion frequency and the increase of the immobile time. Sal provided a protection of in MPTP-induced loss of tyrosine hydroxylase-positive neurons in SNpc and the level of DA, DOPAC, and HVA in the striatum. Furthermore, Sal could increase the phosphorylation level of Akt and GSK3β, upregulate the ratio of Bcl-2/Bax, and inhibit the activation of caspase-3, caspase-6, and caspase-9. These results show that Sal prevents the loss of dopaminergic neurons and the PI3K/Akt/GSK3β pathway signaling pathway may have mediated the protection of Sal against MPTP, suggesting that Sal may be a potential candidate in neuroprotective treatment for PD.

Cholesterol contributes to dopamine-neuronal loss in MPTP mouse model of Parkinson's disease: Involvement of mitochondrial dysfunctions and oxidative stress.

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Rajib Paul

Full Text Available Hypercholesterolemia is a known contributor to the pathogenesis of Alzheimer's disease while its role in the occurrence of Parkinson's disease (PD is only conjecture and far from conclusive. Altered antioxidant homeostasis and mitochondrial functions are the key mechanisms in loss of dopaminergic neurons in the substantia nigra (SN region of the midbrain in PD. Hypercholesterolemia is reported to cause oxidative stress and mitochondrial dysfunctions in the cortex and hippocampus regions of the brain in rodents. However, the impact of hypercholesterolemia on the midbrain dopaminergic neurons in animal models of PD remains elusive. We tested the hypothesis that hypercholesterolemia in MPTP model of PD would potentiate dopaminergic neuron loss in SN by disrupting mitochondrial functions and antioxidant homeostasis. It is evident from the present study that hypercholesterolemia in naïve animals caused dopamine neuronal loss in SN with subsequent reduction in striatal dopamine levels producing motor impairment. Moreover, in the MPTP model of PD, hypercholesterolemia exacerbated MPTP-induced reduction of striatal dopamine as well as dopaminergic neurons in SN with motor behavioral depreciation. Activity of mitochondrial complexes, mainly complex-I and III, was impaired severely in the nigrostriatal pathway of hypercholesterolemic animals treated with MPTP. Hypercholesterolemia caused oxidative stress in the nigrostriatal pathway with increased generation of hydroxyl radicals and enhanced activity of antioxidant enzymes, which were further aggravated in the hypercholesterolemic mice with Parkinsonism. In conclusion, our findings provide evidence of increased vulnerability of the midbrain dopaminergic neurons in PD with hypercholesterolemia.

Cholesterol contributes to dopamine-neuronal loss in MPTP mouse model of Parkinson's disease: Involvement of mitochondrial dysfunctions and oxidative stress.

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Paul, Rajib; Choudhury, Amarendranath; Kumar, Sanjeev; Giri, Anirudha; Sandhir, Rajat; Borah, Anupom

2017-01-01

Hypercholesterolemia is a known contributor to the pathogenesis of Alzheimer's disease while its role in the occurrence of Parkinson's disease (PD) is only conjecture and far from conclusive. Altered antioxidant homeostasis and mitochondrial functions are the key mechanisms in loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain in PD. Hypercholesterolemia is reported to cause oxidative stress and mitochondrial dysfunctions in the cortex and hippocampus regions of the brain in rodents. However, the impact of hypercholesterolemia on the midbrain dopaminergic neurons in animal models of PD remains elusive. We tested the hypothesis that hypercholesterolemia in MPTP model of PD would potentiate dopaminergic neuron loss in SN by disrupting mitochondrial functions and antioxidant homeostasis. It is evident from the present study that hypercholesterolemia in naïve animals caused dopamine neuronal loss in SN with subsequent reduction in striatal dopamine levels producing motor impairment. Moreover, in the MPTP model of PD, hypercholesterolemia exacerbated MPTP-induced reduction of striatal dopamine as well as dopaminergic neurons in SN with motor behavioral depreciation. Activity of mitochondrial complexes, mainly complex-I and III, was impaired severely in the nigrostriatal pathway of hypercholesterolemic animals treated with MPTP. Hypercholesterolemia caused oxidative stress in the nigrostriatal pathway with increased generation of hydroxyl radicals and enhanced activity of antioxidant enzymes, which were further aggravated in the hypercholesterolemic mice with Parkinsonism. In conclusion, our findings provide evidence of increased vulnerability of the midbrain dopaminergic neurons in PD with hypercholesterolemia.

Bauhinia championii Flavone Attenuates Hypoxia-Reoxygenation Induced Apoptosis in H9c2 Cardiomyocytes by Improving Mitochondrial Dysfunction.

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Liao, Ping; Sun, Guibo; Zhang, Chan; Wang, Min; Sun, Yao; Zhou, Yuehan; Sun, Xiaobo; Jian, Jie

2016-11-04

This study aimed to determine the effects of Bauhinia championii flavone (BCF) on hypoxia-reoxygenation (H/R) induced apoptosis in H9c2 cardiomyocytes and to explore potential mechanisms. The H/R model in H9c2 cardiomyocytes was established by 6 h of hypoxia and 12 h of reoxygenation. Cell viability was detected by CCK-8 assay. Apoptotic rate was measured by Annexin V/PI staining. Levels of mitochondria-associated ROS, mitochondrial transmembrane potential (∆Ψm) and mitochondrial permeability transition pores (MPTP) opening were assessed by fluorescent probes. ATP production was measured by ATP assay kit. The release of cytochrome c, translocation of Bax, and related proteins were measured by western blotting. Our results showed that pretreatment with BCF significantly improved cell viability and attenuated the cardiomyocyte apoptosis caused by H/R. Furthermore, BCF increased ATP production and inhibited ROS-generating mitochondria, depolarization of ΔΨm, and MPTP opening. Moreover, BCF pretreatment decreased Bax mitochondrial translocation, cytochrome c release, and activation of caspase-3, as well as increased the expression of p-PI3K, p-Akt, and the ratio of Bcl-2 to Bax. Interestingly, a specific inhibitor of phosphatidylinositol 3-kinase, LY294002, partly reversed the anti-apoptotic effect of BCF. These observations indicated that BCF pretreatment attenuates H/R-induced myocardial apoptosis strength by improving mitochondrial dysfunction via PI3K/Akt signaling pathway.

In vitro and in vivo evidences that antioxidant action contributes to the neuroprotective effects of the neuronal nitric oxide synthase and monoamine oxidase-B inhibitor, 7-nitroindazole.

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Thomas, Bobby; Saravanan, Karuppagounder S; Mohanakumar, Kochupurackal P

2008-05-01

The neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI) is neuroprotective against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Monoamine oxidase (MAO)-B inhibitory action partially contributes to this effect. We tested the hypothesis that 7-NI could be a powerful hydroxyl radical (OH) scavenger, and interferes with oxidative stress caused by MPTP. We measured OH, reduced glutathione (GSH), as well as superoxide dismutase (SOD) and catalase activities in the nucleus caudatus putamen and substantia nigra of Balb/c mice following MPTP and/or 7-NI administration. The nNOS inhibitor caused dose-dependent inhibition in the production of OH in (i) Fenton-like reaction employing ferrous citrate in a cell-free system in test tubes, (ii) in isolated mitochondrial preparation in presence of MPP+, and (iii) in the striatum of mice systemically treated with MPTP. An MPTP-induced depletion of GSH in both the nuclei was blocked by 7-NI, which was dose-dependent (10-50mg/kg), but independent of MAO-B inhibition. The nNOS-mediated recovery of GSH paralleled attenuation of MPTP-induced depletion of striatal dopamine. MPTP-induced increase in the activities of striatal or nigral SOD and catalase were significantly attenuated by 7-NI treatment. These results suggest potent antioxidant action of 7-NI in its neuroprotective effects against MPTP-induced neurotoxicity.

Design and evaluation of mucoadhesive microemulsion for neuroprotective effect of ibuprofen following intranasal route in the MPTP mice model.

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Mandal, Surjyanarayan; Mandal, Snigdha Das; Chuttani, Krishna; Sawant, Krutika K; Subudhi, Bharat Bhushan

2016-08-01

The present study is to investigate the neuroprotective effect of ibuprofen by intranasal administration of mucoadhesive microemulsion (MMEI) against inflammation-mediated by dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease (PD). Ibuprofen-loaded polycarbophil-based MMEI was developed by using response surface methodology (RSM). Ibuprofen with dose of 2.86 mg/kg/day was administered intranasally to male C57BL/6 mice for two consecutive weeks which were pre-treated with four intraperitoneal injections of MPTP (20 mg/kg of body weight) at 2 h intervals. Immunohistochemistry was performed. Optimal MMEI was stable and non-ciliotoxic with 66.29 ± 4.15 nm as average globule size and -20.9 ± 3.98 mV as zeta potential. PDI value and transmission electron microscopy result showed the narrow globule size distribution of MMEI. The result showed that all three independent variables had a significant effect (p open-field test findings revealed the significant improvement in motor performance and gross behavioral activity of the mice. The results from in vivo study and immunohistochemistry showed that nasal administration of Ibuprofen significantly reduced the MPTP-mediated dopamine depletion. Furthermore TH neurons count in the substantia nigra and the density of striatal dopaminergic nerve terminals were found to be significant higher for ibuprofen treated groups. Findings of the investigation revealed that Ibuprofen through developed MMEI was shown to protect neurons against MPTP-induced injury in the Substantia nigra pars compacta (SNpc) and striatum and hence, could be a promising approach for brain targeting of Ibuprofen through intranasal route to treat PD.

Neuroprotective effects of (Val8)GLP-1-Glu-PAL in the MPTP Parkinson's disease mouse model.

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Zhang, YanFang; Chen, YiMei; Li, Lin; Hölscher, Christian

2015-10-15

Glucagon-like peptide 1 (GLP-1) is a hormone and a growth factor. GLP-1 mimetics are currently on the market as treatments for type 2 diabetes. They also have shown neuroprotective properties in animal models of neurodegenerative disorders. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in animal models of Parkinson's disease (PD), and a first clinical trial in PD patients showed promising results. (Val8)GLP-1-glu-PAL is a new GLP-1 analogue which has a longer biological half-life than exendin-4. We previously showed that (Val8)GLP-1-glu-PAL has neuroprotective properties. Here we tested the drug in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected (30mg/kg i.p.) along with (Val8)GLP-1-glu-PAL (25nmol/kg i.p.) once-daily for 8 days. (Val8)GLP-1-glu-PAL showed good effects in preventing the MPTP-induced motor impairment (Rotarod, open field locomotion, swim test), reduction in tyrosine hydroxylase levels (dopamine synthesis) in the substantia nigra, a reduction of activated caspase 3 levels, of TUNEL positive cell numbers, of the pro-apoptotic signaling molecule BAX and an increase in the growth signaling molecule Bcl-2. The results demonstrate that (Val8)GLP-1-glu-PAL shows promise as a novel treatment of PD. Copyright © 2015 Elsevier B.V. All rights reserved.

Biotransformation and neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its two-electron oxidation product, and 1-methyl-4-phenyl-2,3-dihydropyridinium (MPDP+) species

International Nuclear Information System (INIS)

Wu, E.Y.

1989-01-01

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) specifically destroys the nitrostriatal tract in humans and certain laboratory animals, and produces a Parkinsonian syndrome. The mechanism of cellular toxicity induced by the metabolites, however, has not been elucidated. The in vitro and in vivo metabolic behavior of MPTP and MPDP + and the possible role of factors other than MAO in determining the fate of these species was examined. Neuromelanin, which enhanced the rate of oxidation of MPDP + to MPP + , may also act as a reservoir in the substantia nigra to trap MPP + and prolong its exposure to susceptible brain neurons. Diethyldithiocarbamate (DDC), reported to increase the neurotoxic effect of MPTP in mice potentiated the formation of MPDP + from the MAO B catalyzed biotransformation of MPTP and significantly lowered brain dopamine levels in animals pretreated with DDC before MPTP administration. The ability of the dihydropyridinium species to gain access to susceptible neurons via the dopamine uptake system was assessed using the stable, 3,4-dihydro-2-methyl-9-H-indeno [2,1-c]pryidinium (DMIP + ) species. DMIP + , however, proved to be a poor inhibitor of both [ 3 H]dopamine and [ 3 H]MPP + uptake

Exercise Does Not Protect against MPTP-Induced Neurotoxicity in BDNF Happloinsufficent Mice

OpenAIRE

Gerecke, Kim M.; Jiao, Yun; Pagala, Viswajeeth; Smeyne, Richard J.

2012-01-01

Exercise has been demonstrated to potently protect substantia nigra pars compacta (SN) dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. One mechanism proposed to account for this neuroprotection is the upregulation of neurotrophic factors. Several neurotrophic factors, including Brain Derived Neurotrophic Factor (BDNF), have been shown to upregulate in response to exercise. In order to determine if exercise-induced neuroprotection is depende...

Therapeutic effects of arotinolol, a beta-adrenergic blocker, on tremor in MPTP-induced parkinsonian monkeys.

Science.gov (United States)

Kuno, S; Mizuta, E; Nishida, J; Takechi, M

1992-10-01

The effect of arotinolol, a peripherally acting beta-adrenergic-blocking agent, on postural or kinetic tremor was studied in monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Male cynomolgus monkeys (Macaca fascicularis) were treated with three injections of MPTP hydrochloride (0.3 mg/kg, i.v.) at an interval of 3-4 days, followed by several injections of the same dose every 7 days. Four monkeys with persistent parkinsonian symptoms manifested for greater than 1 year were used. The animals developed mild to moderate degrees of postural or kinetic tremor, and their motor activity was reduced. Arotinolol (20-30 mg/kg, s.c.) significantly suppressed postural tremor in a dose-dependent manner. Propranolol (20-30 mg/kg) was also effective in suppressing the tremor. However, the application of propranolol induced emesis, whereas arotinolol had no adverse effects. These results suggest that arotinolol is a useful adjunct to dopaminergic therapy for tremor in Parkinson's disease.

Lack of CCR5 modifies glial phenotypes and population of the nigral dopaminergic neurons, but not MPTP-induced dopaminergic neurodegeneration.

Science.gov (United States)

Choi, Dong-Young; Lee, Myung Koo; Hong, Jin Tae

2013-01-01

Constitutive expression of C-C chemokine receptor (CCR) 5 has been detected in astrocytes, microglia and neurons, but its physiological roles in the central nervous system are obscure. The bidirectional interactions between neuron and glial cells through CCR5 and its ligands were thought to be crucial for maintaining normal neuronal activities. No study has described function of CCR5 in the dopaminergic neurodegeneration in Parkinson's disease. In order to examine effects of CCR5 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration, we employed CCR5 wild type (WT) and knockout (KO) mice. Immunostainings for tyrosine hydroxylase (TH) exhibited that CCR5 KO mice had lower number of TH-positive neurons even in the absence of MPTP. Difference in MPTP (15mg/kg×4 times, 2hr interval)-mediated loss of TH-positive neurons was subtle between CCR5 WT and KO mice, but there was larger dopamine depletion, behavioral impairments and microglial activation in CCR5 deficient mice. Intriguingly, CCR5 KO brains contained higher immunoreactivity for monoamine oxidase (MAO) B which was mainly localized within astrocytes. In agreement with upregulation of MAO B, concentration of MPP+ was higher in the substantia nigra and striatum of CCR5 KO mice after MPTP injection. We found remarkable activation of p38 MAPK in CCR5 deficient mice, which positively regulates MAO B expression. These results indicate that CCR5 deficiency modifies the nigrostriatal dopaminergic neuronal system and bidirectional interaction between neurons and glial cells via CCR5 might be important for dopaminergic neuronal survival. Copyright © 2012 Elsevier Inc. All rights reserved.

Assessment of metabolic changes in the striatum of a MPTP-intoxicated canine model: in vivo ¹H-MRS study of an animal model for Parkinson's disease.

Science.gov (United States)

Choi, Chi-Bong; Kim, Sang-Young; Lee, Sung-Ho; Jahng, Geon-Ho; Kim, Hwi-Yool; Choe, Bo-Young; Ryu, Kyung-Nam; Yang, Dal-Mo; Yim, Sung-Vin; Choi, Woo-Suk

2011-01-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons in the substantia nigra pars compacta, which projects to the striatum. We induced a selective loss of nigrostriatal dopamine neurons, by infusing the mitochondrial complex 1 inhibitor 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) into adult beagle dogs (N=5). Single voxel ¹H water suppressed magnetic resonance spectroscopy (¹H-MRS) at 3 T was used to assess the metabolic changes in the striatum of canine before and after MPTP intoxication. The metabolite spectra obtained from the striatum (voxel size: 2 cm³) showed a lower N-acetyl aspartate to total creatine (creatine+phosphocreatine) ratio after MPTP intoxication. There were no significant differences in other metabolite ratios such as glutamate+glutamine, choline-containing compounds (glycerophosphocholine+phophorylcholine and myo-inositol). Our findings indicated that ¹H-MRS is a sensitive, noninvasive measure of neural toxicity and biochemical alterations of the striatum in a canine model of PD, and further studies are needed to confirm brain metabolic changes in association with progression of MPTP-intoxication. Copyright © 2011 Elsevier Inc. All rights reserved.

Metformin, besides exhibiting strong in vivo anti-inflammatory properties, increases mptp-induced damage to the nigrostriatal dopaminergic system

International Nuclear Information System (INIS)

Ismaiel, Afrah A.K.; Espinosa-Oliva, Ana M.; Santiago, Martiniano; García-Quintanilla, Albert; Oliva-Martín, María J.; Herrera, Antonio J.; Venero, José L.; Pablos, Rocío M. de

2016-01-01

Metformin is a widely used oral antidiabetic drug with known anti-inflammatory properties due to its action on AMPK protein. This drug has shown a protective effect on various tissues, including cortical neurons. The aim of this study was to determine the effect of metformin on the dopaminergic neurons of the substantia nigra of mice using the animal model of Parkinson's disease based on the injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, an inhibitor of the mitochondrial complex I. In vivo and in vitro experiments were used to study the activation of microglia and the damage of the dopaminergic neurons. Our results show that metformin reduced microglial activation measured both at cellular and molecular levels. Rather than protecting, metformin exacerbated dopaminergic damage in response to MPTP. Our data suggest that, contrary to other brain structures, metformin treatment could be deleterious for the dopaminergic system. Hence, metformin treatment may be considered as a risk factor for the development of Parkinson's disease. - Highlights: • Metformin treatment decreases microglial activation in the MPTP model of Parkinson's disease. • Metformin treatment increases the neurodegeneration in the MPTP model of Parkinson's disease, both in vivo and vitro. • Metformin treatment could be a risk factor for the development of Parkinson's disease.

Metformin, besides exhibiting strong in vivo anti-inflammatory properties, increases mptp-induced damage to the nigrostriatal dopaminergic system

Energy Technology Data Exchange (ETDEWEB)

Ismaiel, Afrah A.K.; Espinosa-Oliva, Ana M.; Santiago, Martiniano; García-Quintanilla, Albert; Oliva-Martín, María J.; Herrera, Antonio J.; Venero, José L.; Pablos, Rocío M. de, E-mail: depablos@us.es

2016-05-01

Metformin is a widely used oral antidiabetic drug with known anti-inflammatory properties due to its action on AMPK protein. This drug has shown a protective effect on various tissues, including cortical neurons. The aim of this study was to determine the effect of metformin on the dopaminergic neurons of the substantia nigra of mice using the animal model of Parkinson's disease based on the injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, an inhibitor of the mitochondrial complex I. In vivo and in vitro experiments were used to study the activation of microglia and the damage of the dopaminergic neurons. Our results show that metformin reduced microglial activation measured both at cellular and molecular levels. Rather than protecting, metformin exacerbated dopaminergic damage in response to MPTP. Our data suggest that, contrary to other brain structures, metformin treatment could be deleterious for the dopaminergic system. Hence, metformin treatment may be considered as a risk factor for the development of Parkinson's disease. - Highlights: • Metformin treatment decreases microglial activation in the MPTP model of Parkinson's disease. • Metformin treatment increases the neurodegeneration in the MPTP model of Parkinson's disease, both in vivo and vitro. • Metformin treatment could be a risk factor for the development of Parkinson's disease.

Role of estrogen and levodopa in 1-methyl-4-pheny-l-1, 2, 3, 6-tetrahydropyridine (mptp)-induced cognitive deficit in Parkinsonian ovariectomized mice model: A comparative study.

Science.gov (United States)

Yadav, Satyndra Kumar; Pandey, Shivani; Singh, Babita

2017-11-01

Parkinson's disease (PD) is one of the most common neurodegenerative disease found in the aging population. Currently, many studies are being conducted to find a suitable and effective cure for PD, with an emphasis on the use of herbal plants. In this study, the neuroprotective effects of estrogen was evaluated in the 1-methyl-4-phe-nyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD with cognitive deficit and compared to Levodopa (LD), a well reported neuroprotective agent used for treating PD. Twenty-four Swiss albino mice were randomly divided into four groups: Control, MPTP, MPTP+LD and MPTP+estrogen. The behavioral recovery in both LD and estrogen treated mice were investigated using the rotarod, foot printing, narrow beam walking test and hanging tests. Non-motor behavioral recovery in both LD and estrogen treated were investigated using the Y-maze and Morris water maze. Furthermore, we performed the biochemical test i.e. catalase, lipid and nitrite in prefrontal cortex as well as nigrostriatal region of mouse brain. We also performed the acetylcholine esterase activity in prefrontal cortex and nigrostriatal region of mice brain. The recovery of dopamine neurons in the substantia nigra (SN) region was estimated by immunostaining of tyrosine hydroxylase (TH). Estrogen treatment restored all the deficits induced by MPTP more effectively than levodopa. Estrogen treatment recovered the number of TH-positive cells in both the SN region. Treatment with Estrogen significantly increased the levels of catalase, decreased the level of lipid and nitite in both region SN as well as prefrontal cortex region. Notably, the effect of estrogen was greater than that elicited by levodopa. Acetylcholine esterase activity was significantly increased in MPTP and it was found to be decreased by the treatment of estrogen as well as levodopa, although decrease in the activity was highly significant in estrogen treated group. Our result suggested that estrogen treatment significantly

Pharmacological and Behavioral Enhancement of Neuroplasticity in the MPTP Lesioned Mouse and Nonhuman Primate

Science.gov (United States)

2007-05-01

currently investigating this hypo - thesis in our lab through the administration of specific glutamate receptor antagonists. In conclusion, our study...can involve feeding lesioned nonhuman primates by gavage with an enriched diet , injection of subcutaneous fluids, or the administration of levodopa...during MPTP administration. Supplemental caloric intake may be helpful 10 in improving survival. These studies highlight the systemic effects of

Comparison of the neuroprotective potential of Mucuna pruriens seed extract with estrogen in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model.

Science.gov (United States)

Yadav, Satyndra Kumar; Prakash, Jay; Chouhan, Shikha; Westfall, Susan; Verma, Mradul; Singh, Tryambak Deo; Singh, Surya Pratap

2014-01-01

Parkinson's disease (PD) is one of the most common neurodegenerative disease found in the aging population. Currently, many studies are being conducted to find a suitable and effective cure for PD, with an emphasis on the use of herbal plants. In Ayurveda, Mucuna pruriens (Mp), a leguminous plant, is used as an anti-inflammatory drug. In this study, the neuroprotective effect of an ethanolic extract of Mp seed is evaluated in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD and compared to estrogen, a well reported neuroprotective agent used for treating PD. Twenty-four Swiss albino mice were randomly divided into four groups: Control, MPTP, MPTP+Mp and MPTP+estrogen. The behavioural recovery in both Mp and estrogen treated mice was investigated using the rotarod, foot printing and hanging tests. The recovery of dopamine neurons in the substantia nigra (SN) region was estimated by tyrosine hydroxylase (TH), immunostaining. Additionally inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP) immunoreactivity was evaluated to assess the level of oxidative damage and glial activation respectively. The levels of dopamine and its metabolite in the nigrostriatal region were measured by HPLC. Mp treatment restored all the deficits induced by MPTP more effectively than estrogen. Mp treatment recovered the number of TH-positive cells in both the SN region and the striatum while reducing the expression of iNOS and GFAP in the SN. Treatment with Mp significantly increased the levels of dopamine, DOPAC and homovanillic acid compared to MPTP intoxicated mice. Notably, the effect of Mp was greater than that elicited by estrogen. Mp down regulates NO production, neuroinflammation and microglial activation and all of these actions contribute to Mp's neuroprotective activity. These results suggest that Mp can be an effective treatment for neurodegenerative diseases, especially PD by decreasing oxidative stress and possibly by

Impact of intravenous immunoglobulin on the dopaminergic system and immune response in the acute MPTP mouse model of Parkinson’s disease

Directory of Open Access Journals (Sweden)

St-Amour Isabelle

2012-10-01

Full Text Available Abstract Intravenous immunoglobulin (IVIg is a blood-derived product, used for the treatment of immunodeficiency and autoimmune diseases. Since a range of immunotherapies have recently been proposed as a therapeutic strategy for Parkinson’s disease (PD, we investigated the effects of an IVIg treatment in a neurotoxin-induced animal model of PD. Mice received four injections of MPTP (15 mg/kg at 2-hour intervals followed by a 14-day IVIg treatment, which induced key immune-related changes such as increased regulatory T-cell population and decreased CD4+/CD8+ ratio. The MPTP treatment induced significant 80% and 84% decreases of striatal dopamine concentrations (P P P 

Análise histomorfométrica do músculo sóleo de ratos submetidos ao modelo animal de parkinsonismo induzido pelo MPTP

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Ana Paula Cunha Loureiro

Full Text Available INTRODUÇÃO: Modelos experimentais da Doença de Parkinson (DP que reproduzem a desnervação dopaminérgica têm sido desenvolvidos para estudar a patofisiologia desta doença e analisar a eficácia de novas terapêuticas. Dentre os sinais cardinais da DP temos a rigidez muscular, estudos sugerem que mudanças intrínsecas nas propriedades mecânicas do músculo podem ser responsáveis pelo aumento dessa alteração tônica. OBJETIVO: Analisar a morfologia geral e a histomorfometria do músculo sóleo de ratos Wistar induzidos ao Parkinsonismo por 1-metil-4-fenil-1,2,3,6-tetrahidropiridina (MPTP. MATERIAIS E MÉTODOS: Utilizaram-se 24 ratos Wistar machos, com idade de 13 semanas e peso de 279 ± 13 g, divididos em quatro grupos: 1- controle-controle (n = 6: sham tratados com benserazida + salina; 2 - controle-L-DOPA (n = 6: sham tratados com benserazida + L-DOPA; 3 - MPTP- controle (n = 6: lesão na substância negra (SNc por MPTP tratados com benserazida + salina; 4 - MPTP-L-DOPA (n = 6: lesão na SNc por MPTP tratados com benserazida + L-DOPA. Esses animais foram submetidos a eutanásia 35 dias após os procedimentos experimentais. Foram analisados: peso corporal, peso muscular, morfologia geral do músculo com microscopia de luz e mensuração da área de secção transversa das fibras musculares. Realizaram-se comparações com o teste t pareado entre o peso corporal inicial e final. A ANOVA post-hoc Tukey foi usada para comparações entre os grupos, sendo considerado significativo p ≤ 0,05. RESULTADOS: Não foram encontradas diferenças estatisticamente significativas nas variáveis analisadas. CONCLUSÃO: Os dados analisados não excluem a possibilidade de alterações ocorrerem no interior dessas células, nos tipos de fibras musculares ou em longo prazo.

The monoamine reuptake inhibitor BTS 74 398 fails to evoke established dyskinesia but does not synergise with levodopa in MPTP-treated primates.

Science.gov (United States)

Hansard, Matthew J; Smith, Lance A; Jackson, Michael J; Cheetham, Sharon C; Jenner, Peter

2004-01-01

Long-term treatment of Parkinson's disease (PD) with levodopa (L-dopa) induces dyskinesia that, once established, is provoked by each dose of L-dopa or a dopamine (DA) agonist. In contrast, monoamine reuptake inhibitors may reverse motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates without provoking established involuntary movements. We now examine whether the potent monoamine reuptake blocker BTS 74 398 induces established dyskinesia in MPTP-treated common marmosets primed previously with L-dopa and whether co-administration of BTS 74 398 with L-dopa potentiates motor behaviour and dyskinesia induced by acute L-dopa treatment. Administration of BTS 74 398 (2.5, 5.0, or 10.0 mg/kg, p.o.) in MPTP-treated common marmosets increased locomotor activity and reduced motor disability in a dose-related manner but did not provoke involuntary movements. BTS 74 398 (2.5, 5.0, or 10.0 mg/kg p.o.) co-administered with a threshold dose of L-dopa (2.5 mg/kg p.o.) did not evoke a motor response or induce dyskinesia. Similarly, concomitant administration of BTS 74 398 (5.0 mg/kg p.o.) with a submaximal L-dopa dose (12.5 mg/kg p.o.) did not potentiate the motor response produced by L-dopa alone and there was no alteration in the dyskinesia provoked by L-dopa challenge. BTS 74 398 reverses motor abnormalities in MPTP-treated marmosets without evoking established dyskinesia but no additive improvement occurs when administered in combination with L-dopa. The lack of synergy with L-dopa may suggest different sites of drug action. Copyright 2003 Movement Disorder Society

Biphasic effect of duodenal ulcerogens cysteamine (C), mepirizole (M) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropryridine (MPTP) on gastric emptying in the rat

Energy Technology Data Exchange (ETDEWEB)

Pihan, G.; Kline, T.J.; Szabo, S.

1986-03-01

The effect of acute or chronic administration of duodenal ulcerogens on gastric emptying (GE) of a liquid meal was investigated. In Sprague-Dawley rats (150-200g) 2 ml of /sup 51/Cr in 2% dextrose (5000 CPM) was given intragastrically and the GE half life was established as 7.6 min (controls). In acute experiments, C (30mg/100g), M (40mg/100g) or MPTP (4mg/100g) injected subcutaneously all delayed GE at 1, 2, 4, 8 and 24 hr by 15-77%. Maximal GE delay (p<0.05) by 77, 48 or 71% was found 1, 1 or 2 hr after C, M or MPTP, respectively. In chronic experiments, C (22mg/100g) was given x3 on the first day and once daily (25mg/100g) for 3 or 10 additional days. M (20mg/100g) once daily and MPTP (4mg/100g) x3 daily were given for 4 or 11 days. GE was measured on the 5th and 12th day. Chronically, MPTP accelerated GE by 63 and 31% at 5 and 12 days (p<0.05) and C and M did not change GE. The severity of duodenal ulcers correlated (p<0.05) with the amount of /sup 51/Cr remaining in the stomach: r=-0.68, -0.74 and -0.70 after C, M and MPTP, respectively. Acute administration of duodenal ulcerogens delay GE in rats. Chronic treatment with duodenal ulcerogens either accelerates or does not change GE. The most severe chronic ulcers exhibit the most rapid emptying. The authors data suggest that rapid GE might be a secondary rather than a primary alteration in duodenal ulceration.

Pharmacological and Behavioral Enhancement of Neuroplasticity in the MPTP-Lesioned Mouse and Nonhuman Primate

Science.gov (United States)

2009-05-01

in the clinical rating of these animals. In addition, hypo - kinesia or a general poverty of movement of an ani- mal in its environment is another...Supportive intervention to avoid this adverse effect includes feeding lesioned non-human primates by gavage with an enriched diet , injection of subcu...weight and white blood cell count were the key predic- tors of mortality and should be monitored during MPTP administration. Supplemental caloric

Physical Exercise Modulates L-DOPA-Regulated Molecular Pathways in the MPTP Mouse Model of Parkinson's Disease.

Science.gov (United States)

Klemann, Cornelius J H M; Xicoy, Helena; Poelmans, Geert; Bloem, Bas R; Martens, Gerard J M; Visser, Jasper E

2018-07-01

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in motor and non-motor dysfunction. Physical exercise improves these symptoms in PD patients. To explore the molecular mechanisms underlying the beneficial effects of physical exercise, we exposed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP)-treated mice to a four-week physical exercise regimen, and subsequently explored their motor performance and the transcriptome of multiple PD-linked brain areas. MPTP reduced the number of DA neurons in the SNpc, whereas physical exercise improved beam walking, rotarod performance, and motor behavior in the open field. Further, enrichment analyses of the RNA-sequencing data revealed that in the MPTP-treated mice physical exercise predominantly modulated signaling cascades that are regulated by the top upstream regulators L-DOPA, RICTOR, CREB1, or bicuculline/dalfampridine, associated with movement disorders, mitochondrial dysfunction, and epilepsy-related processes. To elucidate the molecular pathways underlying these cascades, we integrated the proteins encoded by the exercise-induced differentially expressed mRNAs for each of the upstream regulators into a molecular landscape, for multiple key brain areas. Most notable was the opposite effect of physical exercise compared to previously reported effects of L-DOPA on the expression of mRNAs in the SN and the ventromedial striatum that are involved in-among other processes-circadian rhythm and signaling involving DA, neuropeptides, and endocannabinoids. Altogether, our findings suggest that physical exercise can improve motor function in PD and may, at the same time, counteract L-DOPA-mediated molecular mechanisms. Further, we hypothesize that physical exercise has the potential to improve non-motor symptoms of PD, some of which may be the result of (chronic) L-DOPA use.

Neuroprotective effects of riluzole in early phase Parkinson's disease on clinically relevant parameters in the marmoset MPTP model

NARCIS (Netherlands)

Verhave, P.S.; Jongsma, M.J.; Berg, R.M. van den; Vanwersch, R.A.P.; Smit, A.B.; Philippens, I.H.C.H.M.

2012-01-01

The present study evaluates neuroprotection in a marmoset MPTP (1-methyl-1,2,3,6-tetrahydropyridine) model representing early Parkinson's disease (PD). The anti-glutamatergic compound riluzole is used as a model compound for neuroprotection. The compound is one of the few protective compounds used

Synthetic bovine proline-rich-polypeptides generate hydroxyl radicals and fail to protect dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity in mice.

Science.gov (United States)

Knaryan, Varduhi H; Samantaray, Supriti; Varghese, Merina; Srinivasan, Ambika; Galoyan, Armen A; Mohanakumar, Kochupurackal P

2006-08-01

Proline-rich-polypeptides (PRPs) isolated from bovine hypothalamus have been shown to render protection against neuronal injury of the brain and spinal cord. We examined two PRPs containing 15 and 10 amino acid residues (PRP-1 and PRP-4 synthetic polypeptide) for their effect, if any, on dopaminergic neuronal damage caused by the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Effects of these PRPs on hydroxyl radical ((*)OH) generation in a Fenton-like reaction as well as from isolated mitochondria were monitored, employing a sensitive salicylate hydroxylation procedure. Balb/c mice treated (i.p., twice, 16 h apart) with MPTP (30 mg/kg) or PRP-1 (1.6 mg/kg), but not PRP-4 (1.6 mg/kg) showed significant loss of striatal dopamine and norepinephrine as assayed by an HPLC-electrochemical procedure. Pretreatment with the PRPs, 30 min prior to the neurotoxin administration failed to attenuate MPTP-induced striatal dopamine or norepinephrine depletion, but significantly attenuated the MPTP-induced decrease in dopamine turnover. A significant increase in the generation of (*)OH by the PRPs in a Fenton-like reaction or from isolated mitochondria suggests their pro-oxidant action, and explains their failure to protect against MPTP-induced parkinsonism in mice.

Protection but maintained dysfunction of nigral dopaminergic nerve cell bodies and striatal dopaminergic terminals in MPTP-lesioned mice after acute treatment with the mGluR5 antagonist MPEP.

Science.gov (United States)

Aguirre, Jose A; Kehr, Jan; Yoshitake, Takashi; Liu, Fang-Ling; Rivera, Alicia; Fernandez-Espinola, Sergio; Andbjer, Beth; Leo, Giuseppina; Medhurst, Andrew D; Agnati, Luigi F; Fuxe, Kjell

2005-02-08

The mGluR5 antagonist MPEP was used to study the role of mGluR5 in MPTP-induced injury of the nigrostriatal DA neurons. The findings indicate that acute blockade of mGluR5 may result in neuroprotective actions against MPTP neurotoxicity on nigral DA cell bodies and striatal DA terminals using stereological analysis of TH immunoreactivity and microdensitometry. Biochemical analysis showed no restoration of DA levels and metabolism indicating a maintained reduction of DA transmission.

Protective Effects of Streblus asper Leaf Extract on H2O2-Induced ROS in SK-N-SH Cells and MPTP-Induced Parkinson’s Disease-Like Symptoms in C57BL/6 Mouse

Directory of Open Access Journals (Sweden)

Kanathip Singsai

2015-01-01

Full Text Available This study investigated the effects of Streblus asper leaf extract (SA on reactive oxygen species (ROS in SK-N-SH cell culture and on motor functions and behaviors in MPTP-treated C57BL/6 mice. SK-N-SH cell viability after incubation with SA for 24 h was measured by MTT assay. Intracellular ROS levels of SK-N-SH cells were quantified after pretreatment with SA (0, 200, 600, and 1000 µg/mL in the presence of H2O2 (300 µM. Male C57BL/6 mice were force-fed with water or 200 mg/kg/day SA for 32 days. Intraperitoneal injection of MPTP was used to induce Parkinson’s disease-like symptoms. Catalepsy, beam balance ability, olfactory discrimination, social recognition, and spontaneous locomotor activity were assessed on days 19, 21, 23, 26, and 32, respectively. In cell culture, SA at 200, 600, and 1000 µg/mL significantly decreased ROS levels in H2O2-treated SK-N-SH cells. MPTP-treated C57BL/6 mice showed a significant change in all parameters tested when compared to the control group. Pretreatment and concurrent treatment with 200 mg/kg/day SA could antagonize the motor and cognitive function deficits induced by MPTP. The results show that SA possesses anti-Parkinson effects in MPTP-treated C57BL/6 mice and that reduction in ROS levels might be one of the mechanisms.

Lycium barbarum Polysaccharide Promotes Nigrostriatal Dopamine Function by Modulating PTEN/AKT/mTOR Pathway in a Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Murine Model of Parkinson's Disease.

Science.gov (United States)

Wang, Xiaohong; Pang, Lei; Zhang, Yanqing; Xu, Jiang; Ding, Dongyi; Yang, Tianli; Zhao, Qian; Wu, Fan; Li, Fei; Meng, Haiwei; Yu, Duonan

2018-04-01

To investigate the effects of Lycium barbarum polysaccharide (LBP) on pathological symptoms and behavioral deficits in a Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. The therapeutic effects of LBP were monitored with an Open field test, a Rotarod test and a Morris water maze test. We also investigated the mechanisms with qRT-PCR and Western blotting analyses. After a relatively short-term LBP treatment, the total distance and walking time of PD mice significantly increased. The staying duration on the rod of PD mice increased in the Rotarod test. LBP can up-regulate levels of SOD2, CAT and GPX1 and inhibit the abnormal aggregation of α-synuclein induced by MPTP. LBP treatment can also up-regulate the phosphorylation of AKT and mTOR, and may play its protective role by activating the PTEN/AKT/mTOR signaling axis. These results suggest that LBP can effectively alleviate the degeneration in the nigrostriatal system induced by MPTP treatment. It may be a potential candidate for the treatment of Parkinson's disease.

Involvment of cytosolic and mitochondrial GSK-3beta in mitochondrial dysfunction and neuronal cell death of MPTP/MPP-treated neurons.

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Agnès Petit-Paitel

Full Text Available Aberrant mitochondrial function appears to play a central role in dopaminergic neuronal loss in Parkinson's disease (PD. 1-methyl-4-phenylpyridinium iodide (MPP(+, the active metabolite of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, is a selective inhibitor of mitochondrial complex I and is widely used in rodent and cell models to elicit neurochemical alterations associated with PD. Recent findings suggest that Glycogen Synthase Kinase-3beta (GSK-3beta, a critical activator of neuronal apoptosis, is involved in the dopaminergic cell death. In this study, the role of GSK-3beta in modulating MPP(+-induced mitochondrial dysfunction and neuronal death was examined in vivo, and in two neuronal cell models namely primary cultured and immortalized neurons. In both cell models, MPTP/MPP(+ treatment caused cell death associated with time- and concentration-dependent activation of GSK-3beta, evidenced by the increased level of the active form of the kinase, i.e. GSK-3beta phosphorylated at tyrosine 216 residue. Using immunocytochemistry and subcellular fractionation techniques, we showed that GSK-3beta partially localized within mitochondria in both neuronal cell models. Moreover, MPP(+ treatment induced a significant decrease of the specific phospho-Tyr216-GSK-3beta labeling in mitochondria concomitantly with an increase into the cytosol. Using two distinct fluorescent probes, we showed that MPP(+ induced cell death through the depolarization of mitochondrial membrane potential. Inhibition of GSK-3beta activity using well-characterized inhibitors, LiCl and kenpaullone, and RNA interference, prevented MPP(+-induced cell death by blocking mitochondrial membrane potential changes and subsequent caspase-9 and -3 activation. These results indicate that GSK-3beta is a critical mediator of MPTP/MPP(+-induced neurotoxicity through its ability to regulate mitochondrial functions. Inhibition of GSK-3beta activity might provide protection against

A novel GLP-1/GIP dual agonist is more effective than liraglutide in reducing inflammation and enhancing GDNF release in the MPTP mouse model of Parkinson's disease.

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Yuan, Ziyue; Li, Dongfang; Feng, Peng; Xue, Guofang; Ji, Chenhui; Li, Guanglai; Hölscher, Christian

2017-10-05

Type 2 diabetes mellitus (T2DM) is one of the risk factors for Parkinson's disease (PD). Insulin desensitisation has been observed in the brains of patients, which may promote neurodegeneration. Incretins are a family of growth factors that can re-sensitise insulin signalling. We have previously shown that mimetics of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP) mouse model of PD. Recently, dual GLP-1/GIP receptor agonists have been developed. We therefore tested the novel dual agonist DA3-CH in comparison with the best GLP-1 analogue currently on the market, liraglutide (both drugs 25nmol/kg ip once-daily for 7 days) in the MPTP mouse model of PD (25mg/kg ip once-daily for 7 days). In the Rotarod and grip strength assessment, DA3-CH was superior to liraglutide in reversing the MPTP-induced motor impairment. Dopamine synthesis as indicated by levels of tyrosine hydroxylase was much reduced by MPTP in the substantia nigra and striatum, and DA3-CH reversed this while liragutide only partially reversed this. The chronic inflammation response as shown in increased levels of activated microglia and astrocytes was reduced by both drugs. Importantly, expression levels of the neuroprotective growth factor Glial Derived Neurotrophic Factor (GDNF) was much enhanced by both DA3-CH and liragutide. The results demonstrate that the combination of GLP-1 and GIP receptor activation is superior to single GLP-1 receptor activation alone. Therefore, new dual agonists may be a promising treatment for PD. The GLP-1 receptor agonist exendin-4 has already shown disease modifying effects in clinical trials in PD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

DJ-1-dependent protective activity of DJ-1-binding compound no. 23 against neuronal cell death in MPTP-treated mouse model of Parkinson's disease

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Kazuko Takahashi-Niki

2015-03-01

Full Text Available Parkinson's disease (PD is caused by dopaminergic cell death in the substantia nigra, leading to a reduced level of dopamine in the striatum. Oxidative stress is one of the causes of PD. Since symptomatic PD therapies are used, identification of compounds or proteins that inhibit oxidative stress-induced neuronal cell death is necessary. DJ-1 is a causative gene product of familial PD and plays a role in anti-oxidative stress reaction. We have identified various DJ-1-binding compounds, including compound-23, that restored neuronal cell death and locomotion defects observed in neurotoxin-induced PD models. In this study, wild-type and DJ-1-knockout mice were injected intraperitoneally with 1 mg/kg of compound-23 and then with 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP at 1 h after injection. Five days after administration, the effects of compound-23 on MPTP-induced locomotion deficits, on dopaminergic cell death and on brain dopamine levels were analyzed by rotor rod tests, by staining cells with an anti-TH antibody and by an HPLC, respectively. The results showed that compound-23 inhibited MPTP-induced reduction of retention time on the rotor rod bar, neuronal cell death in the substantia nigra and striatum and dopamine content in wild-type mice but not in DJ-1-knockout mice, indicating a DJ-1-dependent effect of compound-23.

Roles of thioredoxin in nitric oxide-dependent preconditioning-induced tolerance against MPTP neurotoxin

International Nuclear Information System (INIS)

Chiueh, C.C.; Andoh, Tsugunobu; Chock, P. Boon

2005-01-01

Hormesis, a stress tolerance, can be induced by ischemic preconditioning stress. In addition to preconditioning, it may be induced by other means, such as gas anesthetics. Preconditioning mechanisms, which may be mediated by reprogramming survival genes and proteins, are obscure. A known neurotoxicant, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), causes less neurotoxicity in the mice that are preconditioned. Pharmacological evidences suggest that the signaling pathway of ·NO-cGMP-PKG (protein kinase G) may mediate preconditioning phenomenon. We developed a human SH-SY5Y cell model for investigating · NO-mediated signaling pathway, gene regulation, and protein expression following a sublethal preconditioning stress caused by a brief 2-h serum deprivation. Preconditioned human SH-SY5Y cells are more resistant against severe oxidative stress and apoptosis caused by lethal serum deprivation and 1-mehtyl-4-phenylpyridinium (MPP + ). Both sublethal and lethal oxidative stress caused by serum withdrawal increased neuronal nitric oxide synthase (nNOS/NOS1) expression and · NO levels to a similar extent. In addition to free radical scavengers, inhibition of nNOS, guanylyl cyclase, and PKG blocks hormesis induced by preconditioning. S-nitrosothiols and 6-Br-cGMP produce a cytoprotection mimicking the action of preconditioning tolerance. There are two distinct cGMP-mediated survival pathways: (i) the up-regulation of a redox protein thioredoxin (Trx) for elevating mitochondrial levels of antioxidant protein Mn superoxide dismutase (MnSOD) and antiapoptotic protein Bcl-2, and (ii) the activation of mitochondrial ATP-sensitive potassium channels [K(ATP)]. Preconditioning induction of Trx increased tolerance against MPP + , which was blocked by Trx mRNA antisense oligonucleotide and Trx reductase inhibitor. It is concluded that Trx plays a pivotal role in · NO-dependent preconditioning hormesis against MPTP/MPP +

TFP5/TP5 peptide provides neuroprotection in the MPTP model of Parkinson′s disease

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B K Binukumar

2016-01-01

Full Text Available Cyclin-dependent kinase 5 (Cdk5 is a member of the serine-threonine kinase family of cyclin-dependent kinases. Cdk5 is critical to normal mammalian nervous system development and plays important regulatory roles in multiple cellular functions. Recent evidence indicates that Cdk5 is inappropriately activated in several neurodegenerative conditions, including Parkinson′s disease (PD. PD is a chronic neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunction. During neurotoxicity, p35 is cleaved to form p25. Binding of p25 with Cdk5 leads deregulation of Cdk5 resulting in number of neurodegenerative pathologies. To date, strategies to specifically inhibit Cdk5 hyperactivity have not been successful without affecting normal Cdk5 activity. Here we show that inhibition of p25/Cdk5 hyperactivation through TFP5/TP5, truncated 24-aa peptide derived from the Cdk5 activator p35 rescues nigrostriatal dopaminergic neurodegeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP/MPP + in a mouse model of PD. TP5 peptide treatment also blocked dopamine depletion in the striatum and improved gait dysfunction after MPTP administration. The neuroprotective effect of TFP5/TP5 peptide is also associated with marked reduction in neuroinflammation and apoptosis. Here we show inhibition of Cdk5/p25-hyperactivation by TFP5/TP5 peptide, which identifies Cdk5/p25 as a potential therapeutic target to reduce neurodegeneration in PD.

Iron Chelators and Antioxidants Regenerate Neuritic Tree and Nigrostriatal Fibers of MPP+/MPTP-Lesioned Dopaminergic Neurons.

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Pabla Aguirre

Full Text Available Neuronal death in Parkinson's disease (PD is often preceded by axodendritic tree retraction and loss of neuronal functionality. The presence of non-functional but live neurons opens therapeutic possibilities to recover functionality before clinical symptoms develop. Considering that iron accumulation and oxidative damage are conditions commonly found in PD, we tested the possible neuritogenic effects of iron chelators and antioxidant agents. We used three commercial chelators: DFO, deferiprone and 2.2'-dypyridyl, and three 8-hydroxyquinoline-based iron chelators: M30, 7MH and 7DH, and we evaluated their effects in vitro using a mesencephalic cell culture treated with the Parkinsonian toxin MPP+ and in vivo using the MPTP mouse model. All chelators tested promoted the emergence of new tyrosine hydroxylase (TH-positive processes, increased axodendritic tree length and protected cells against lipoperoxidation. Chelator treatment resulted in the generation of processes containing the presynaptic marker synaptophysin. The antioxidants N-acetylcysteine and dymetylthiourea also enhanced axodendritic tree recovery in vitro, an indication that reducing oxidative tone fosters neuritogenesis in MPP+-damaged neurons. Oral administration to mice of the M30 chelator for 14 days after MPTP treatment resulted in increased TH- and GIRK2-positive nigra cells and nigrostriatal fibers. Our results support a role for oral iron chelators as good candidates for the early treatment of PD, at stages of the disease where there is axodendritic tree retraction without neuronal death.

Metabolic Disturbances in the Striatum and Substantia Nigra in the Onset and Progression of MPTP-Induced Parkinsonism Model

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Yi Lu

2018-02-01

Full Text Available Metabolic confusion has been linked to the pathogenesis of Parkinson's disease (PD, while the dynamic changes associated with the onset and progression of PD remain unclear. Herein, dynamic changes in metabolites were detected from the initiation to the development of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP -induced Parkinsonism model to elucidate its potential metabolic mechanism. Ex vivo1H nuclear magnetic resonance (NMR spectroscopy was used to measure metabolite changes in the striatum and substantia nigra (SN of mice at 1, 7, and 21 days after injection of MPTP. Metabolomic analysis revealed a clear separation of the overall metabolites between PD and control mice at different time points. Glutamate (Glu in the striatum was significantly elevated at induction PD day 1 mice, which persisted to day 21. N-acetylaspartate (NAA increased in the striatum of induction PD mice on days 1 and 7, but no significant difference was found in striatum on day 21. Myo-Inositol (mI and taurine (Tau were also disturbed in the striatum in induction PD day 1 mice. Additionally, key enzymes in the glutamate-glutamine cycle were significantly increased in PD mice. These findings suggest that neuron loss and motor function impairment in induction PD mice may be linked to overactive glutamate-glutamine cycle and altered membrane metabolism.

Decreased Rhes mRNA levels in the brain of patients with Parkinson's disease and MPTP-treated macaques.

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Francesco Napolitano

Full Text Available In rodent and human brains, the small GTP-binding protein Rhes is highly expressed in virtually all dopaminoceptive striatal GABAergic medium spiny neurons, as well as in large aspiny cholinergic interneurons, where it is thought to modulate dopamine-dependent signaling. Consistent with this knowledge, and considering that dopaminergic neurotransmission is altered in neurological and psychiatric disorders, here we sought to investigate whether Rhes mRNA expression is altered in brain regions of patients with Parkinson's disease (PD, Schizophrenia (SCZ, and Bipolar Disorder (BD, when compared to healthy controls (about 200 post-mortem samples. Moreover, we performed the same analysis in the putamen of non-human primate Macaca Mulatta, lesioned with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP. Overall, our data indicated comparable Rhes mRNA levels in the brain of patients with SCZ and BD, and their respective healthy controls. In sharp contrast, the putamen of patients suffering from PD showed a significant 35% reduction of this transcript, compared to healthy subjects. Interestingly, in line with observations obtained in humans, we found 27% decrease in Rhes mRNA levels in the putamen of MPTP-treated primates. Based on the established inhibitory influence of Rhes on dopamine-related responses, we hypothesize that its striatal downregulation in PD patients and animal models of PD might represent an adaptive event of the dopaminergic system to functionally counteract the reduced nigrostriatal innervation.

Neuroprotective effect of bee venom is mediated by reduced astrocyte activation in a subchronic MPTP-induced model of Parkinson's disease.

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Kim, Mi Eun; Lee, Joo Yeon; Lee, Kyung Moon; Park, Hee Ra; Lee, Eunjin; Lee, Yujeong; Lee, Jun Sik; Lee, Jaewon

2016-08-01

Bee venom (BV), also known as apitoxin, is widely used in traditional oriental medicine to treat immune-related diseases. Recent studies suggest that BV could be beneficial for the treatment of neurodegenerative diseases. Parkinson's disease (PD) is the second most common neurodegenerative disease next to Alzheimer's disease, and PD pathologies are closely associated with neuroinflammation. Previous studies have suggested the neuroprotective effects of BV in animal models of PD are due to the modulation of inflammation. However, the molecular mechanisms responsible for the anti-neuroinflammatory effect of BV have not been elucidated in astrocytes. Here, the authors investigated the neuroprotective effects of BV and pramipexole (PPX; a positive control) in a subchronic MPTP-induced murine PD model. Both BV and PPX prevented MPTP-induced impairments in motor performance and reduced dopaminergic neuron loss, and furthermore, these neuroprotective effects of BV and PPX were found to be associated with reduced astroglial activation in vivo PD model. However, in MPP(+) treated primary cultured astrocytes, BV modulated astrocyte activation, whereas PPX did not, indicating that the neuroprotective effects of PPX were not mediated by neuroinflammation. These findings suggest that BV should be considered a potential therapeutic or preventive agent for PD and other neuroinflammatory associated disorders.

Nicotine suppresses the neurotoxicity by MPP+/MPTP through activating α7nAChR/PI3K/Trx-1 and suppressing ER stress.

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Cai, Yanxue; Zhang, Xianwen; Zhou, Xiaoshuang; Wu, Xiaoli; Li, Yanhui; Yao, Jianhua; Bai, Jie

2017-03-01

Parkinson's disease (PD) is a neurodegenerative disease. Nicotine has been reported to have the role in preventing Parkinson's disease. However, its mechanism is still unclear. In present study we found that nicotine suppressed 1-methyl-4-phenylpyridinium ion(MPP + ) toxicity in PC12 cells by MTT assay. The expression of thioredoxin-1(Trx-1) was decreased by MPP + , which was restored by nicotine. The nicotine suppressed expressions of Glucose-regulated protein 78(GRP78/Bip) and C/EBP homologous protein (CHOP) induced by MPP + . The methyllycaconitine (MLA), the inhibitor of α7nAChR and LY294002, the inhibitor of phosphatidylinositol 3-kinase (PI3K) blocked the suppressions of above molecules, respectively. Consistently, pretreatment with nicotine ameliorated the motor ability, restored the declines of Trx-1 and tyrosine hydroxylase (TH), and suppressed the expressions of Bip and CHOP induced by 1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Our results suggest that nicotine plays role in resisting MPP + /MPTP neurotoxicity through activating the α7nAChR/PI3K/Trx-1 pathway and suppressing ER stress. Copyright © 2017 Elsevier B.V. All rights reserved.

Caspase-1 Deficiency Alleviates Dopaminergic Neuronal Death via Inhibiting Caspase-7/AIF Pathway in MPTP/p Mouse Model of Parkinson's Disease.

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Qiao, Chen; Zhang, Lin-Xia; Sun, Xi-Yang; Ding, Jian-Hua; Lu, Ming; Hu, Gang

2017-08-01

Caspase family has been recognized to be involved in dopaminergic (DA) neuronal death and to exert an unfavorable role in Parkinson's disease (PD) pathology. Our previous study has revealed that caspase-1, as an important component of NLRP3 inflammasome, induces microglia-mediated neuroinflammation in the pathogenesis of PD. However, the role of caspase-1 in DA neuronal degeneration in the onset of PD remains unclear. Here, we showed that caspase-1 knockout ameliorated DA neuronal loss and dyskinesia in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine/probenecid (MPTP/p)-induced PD model mice. We further found that caspase-1 knockout decreased MPTP/p-induced caspase-7 cleavage, subsequently inhibited nuclear translocation of poly (ADP-ribose) polymerase 1 (PARP1), and reduced the release of apoptosis-inducing factor (AIF). Consistently, we demonstrated that caspase-1 inhibitor suppressed caspase-7/PARP1/AIF-mediated apoptosis pathway by 1-methyl-4-phenylpyridinium ion (MPP + ) stimulation in SH-SY5Y cells. Caspase-7 overexpression reduced the protective effects of caspase-1 inhibitor on SH-SY5Y cell apoptosis. Collectively, our results have revealed that caspase-1 regulates DA neuronal death in the pathogenesis of PD in mice via caspase-7/PARP1/AIF pathway. These findings will shed new insight into the potential of caspase-1 as a target for PD therapy.

extract attenuates MPTP-induced oxidative stress and behavioral

African Journals Online (AJOL)

on oxidative stress levels were assessed by estimating enzyme status, including superoxide dismutase. (SOD), catalase ... in both non-human primates and mice models. [12,13]. ..... Polyphenol composition and antioxidant activity of cumin.

Pharmacologic antagonism of dopamine receptor D3 attenuates neurodegeneration and motor impairment in a mouse model of Parkinson's disease.

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Elgueta, Daniela; Aymerich, María S; Contreras, Francisco; Montoya, Andro; Celorrio, Marta; Rojo-Bustamante, Estefanía; Riquelme, Eduardo; González, Hugo; Vásquez, Mónica; Franco, Rafael; Pacheco, Rodrigo

2017-02-01

Neuroinflammation involves the activation of glial cells, which is associated to the progression of neurodegeneration in Parkinson's disease. Recently, we and other researchers demonstrated that dopamine receptor D3 (D3R)-deficient mice are completely refractory to neuroinflammation and consequent neurodegeneration associated to the acute intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this study we examined the therapeutic potential and underlying mechanism of a D3R-selective antagonist, PG01037, in mice intoxicated with a chronic regime of administration of MPTP and probenecid (MPTPp). Biodistribution analysis indicated that intraperitoneally administered PG01037 crosses the blood-brain barrier and reaches the highest concentration in the brain 40 min after the injection. Furthermore, the drug was preferentially distributed to the brain in comparison to the plasma. Treatment of MPTPp-intoxicated mice with PG01037 (30 mg/kg, administrated twice a week for five weeks) attenuated the loss of dopaminergic neurons in the substantia nigra pars compacta, as evaluated by stereological analysis, and the loss of striatal dopaminergic terminals, as determined by densitometric analyses of tyrosine hydroxylase and dopamine transporter immunoreactivities. Accordingly, the treatment resulted in significant improvement of motor performance of injured animals. Interestingly, the therapeutic dose of PG01037 exacerbated astrogliosis and resulted in increased ramification density of microglial cells in the striatum of MPTPp-intoxicated mice. Further analyses suggested that D3R expressed in astrocytes favours a beneficial astrogliosis with anti-inflammatory consequences on microglia. Our findings indicate that D3R-antagonism exerts a therapeutic effect in parkinsonian animals by reducing the loss of dopaminergic neurons in the nigrostriatal pathway, alleviating motor impairments and modifying the pro-inflammatory phenotype of glial cells. Copyright �

Attenuation of Ca2+ homeostasis, oxidative stress, and mitochondrial dysfunctions in diabetic rat heart: insulin therapy or aerobic exercise?

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da Silva, Márcia F; Natali, Antônio J; da Silva, Edson; Gomes, Gilton J; Teodoro, Bruno G; Cunha, Daise N Q; Drummond, Lucas R; Drummond, Filipe R; Moura, Anselmo G; Belfort, Felipe G; de Oliveira, Alessandro; Maldonado, Izabel R S C; Alberici, Luciane C

2015-07-15

We tested the effects of swimming training and insulin therapy, either alone or in combination, on the intracellular calcium ([Ca(2+)]i) homeostasis, oxidative stress, and mitochondrial functions in diabetic rat hearts. Male Wistar rats were separated into control, diabetic, or diabetic plus insulin groups. Type 1 diabetes mellitus was induced by streptozotocin (STZ). Insulin-treated groups received 1 to 4 UI of insulin daily for 8 wk. Each group was divided into sedentary or exercised rats. Trained groups were submitted to swimming (90 min/day, 5 days/wk, 8 wk). [Ca(2+)]i transient in left ventricular myocytes (LVM), oxidative stress in LV tissue, and mitochondrial functions in the heart were assessed. Diabetes reduced the amplitude and prolonged the times to peak and to half decay of the [Ca(2+)]i transient in LVM, increased NADPH oxidase-4 (Nox-4) expression, decreased superoxide dismutase (SOD), and increased carbonyl protein contents in LV tissue. In isolated mitochondria, diabetes increased Ca(2+) uptake, susceptibility to permeability transition pore (MPTP) opening, uncoupling protein-2 (UCP-2) expression, and oxygen consumption but reduced H2O2 release. Swimming training corrected the time course of the [Ca(2+)]i transient, UCP-2 expression, and mitochondrial Ca(2+) uptake. Insulin replacement further normalized [Ca(2+)]i transient amplitude, Nox-4 expression, and carbonyl content. Alongside these benefits, the combination of both therapies restored the LV tissue SOD and mitochondrial O2 consumption, H2O2 release, and MPTP opening. In conclusion, the combination of swimming training with insulin replacement was more effective in attenuating intracellular Ca(2+) disruptions, oxidative stress, and mitochondrial dysfunctions in STZ-induced diabetic rat hearts. Copyright © 2015 the American Physiological Society.

Substantia nigra in MR images in Parkinson disease and MPTP exposure

International Nuclear Information System (INIS)

De La Paz, R.L.; Duguid, J.; Langston, W.J.

1986-01-01

Eight patients, aged 60-77 years, with idiopathic Parkinson disease were studied to determine whether the characteristic degeneration of the substantia nigra (zona compacta), seen pathologically, could be identified in vivo on T2-weighted proton MR imaging (1.5 T). The mean width of the substantia nigra in the eight patients was 4.1 mm (SEM = 0.21 mm), significantly (rho < .004) less than the mean width of 5.2 mm (SEM= 0.30 mm) in ten age-matched controls. Overlap with control values was seen in only one patient. No clear correlation between low signal in the putamen (suggesting excess deposition of iron, Fe/sup 3+/) and Parkinson disease was seen. Narrowing of the substantia nigra on MR imaging was also seen in one patient with drug-induced Parkinson syndrome (MPTP exposure). These changes on MR imaging are probably due to atrophy of the zona compacta of the substantia nigra, but excess iron in the zona reticulata may partially contribute to these findings. MR imaging may be useful for differentiating ''classic'' Parkinson disease from other extrapyramidal degenerative disorders and for predicting response to drug therapy

Anti-inflammatory and neuroprotective effects of an orally active apocynin derivative in pre-clinical models of Parkinson’s disease

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Ghosh Anamitra

2012-10-01

Full Text Available Abstract Background Parkinson’s disease (PD is a devastating neurodegenerative disorder characterized by progressive motor debilitation, which affects several million people worldwide. Recent evidence suggests that glial cell activation and its inflammatory response may contribute to the progressive degeneration of dopaminergic neurons in PD. Currently, there are no neuroprotective agents available that can effectively slow the disease progression. Herein, we evaluated the anti-inflammatory and antioxidant efficacy of diapocynin, an oxidative metabolite of the naturally occurring agent apocynin, in a pre-clinical 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mouse model of PD. Methods Both pre-treatment and post-treatment of diapocynin were tested in the MPTP mouse model of PD. Diapocynin was administered via oral gavage to MPTP-treated mice. Following the treatment, behavioral, neurochemical and immunohistological studies were performed. Neuroinflammatory markers, such as ionized calcium binding adaptor molecule 1 (Iba-1, glial fibrillary acidic protein (GFAP, gp91phox and inducible nitric oxide synthase (iNOS, were measured in the nigrostriatal system. Nigral tyrosine hydroxylase (TH-positive neurons as well as oxidative markers 3-nitrotyrosine (3-NT, 4-hydroxynonenal (4-HNE and striatal dopamine levels were quantified for assessment of the neuroprotective efficacy of diapocynin. Results Oral administration of diapocynin significantly attenuated MPTP-induced microglial and astroglial cell activation in the substantia nigra (SN. MPTP-induced expression of gp91phox and iNOS activation in the glial cells of SN was also completely blocked by diapocynin. Notably, diapocynin markedly inhibited MPTP-induced oxidative markers including 3-NT and 4-HNE levels in the SN. Treatment with diapocynin also significantly improved locomotor activity, restored dopamine and its metabolites, and protected dopaminergic neurons and their nerve terminals in

Antihepatotoxic activity and chemical constituents of Buddleja asiatica Lour.

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El-Domiaty, Maher M; Wink, Michael; Abdel Aal, Mahmoud M; Abou-Hashem, Maged M; Abd-Alla, Rehab H

2009-01-01

A new natural compound, named 6-O-(3",4"-dimethoxycinnamoyl) catalpol, was isolated from the defatted alcoholic extract of the flowering parts of Buddleja asiatica Lour. (family Scrophulariaceae). Other separated known compounds included steroids (beta-sitosterol, stigmasterol, stigmasterol-O-glucoside, beta-sitosterol-O-glucoside), iridoid glucosides (methyl catalpol, catalpol, aucubin), phenylpropanoids (isoacteoside and acteoside), a triterpene saponin (mimengoside A), flavonoids (diosmin and linarin) in addition to the free sugars mannitol and sucrose. The structures of the isolated compounds were established by 1H and 13C NMR and mass spectrometry. Furthermore, the polar fraction of the flowering parts and the roots showed substantial antihepatotoxic activity comparable to that of the lignan silymarin.

Reversible Pharmacological Induction of Motor Symptoms in MPTP-Treated Mice at the Presymptomatic Stage of Parkinsonism: Potential Use for Early Diagnosis of Parkinson's Disease.

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Khakimova, Gulnara R; Kozina, Elena A; Kucheryanu, Valerian G; Ugrumov, Michael V

2017-07-01

A crucial event in the pathogenesis of Parkinson's disease is the death of dopaminergic neurons of the nigrostriatal system, which are responsible for the regulation of motor function. Motor symptoms first appear in patients 20-30 years after the onset of the neurodegeneration, when there has been a loss of an essential number of neurons and depletion of compensatory reserves of the brain, which explains the low efficiency of treatment. Therefore, the development of a technology for the diagnosing of Parkinson's disease at the preclinical stage is of a high priority in neurology. In this study, we have developed at an experimental model a fundamentally novel for neurology approach for diagnosis of Parkinson's disease at the preclinical stage. This methodology, widely used for the diagnosis of chronic diseases in the internal medicine, is based on the application of a challenge test that temporarily increases the latent failure of a specific functional system, thereby inducing the short-term appearance of clinical symptoms. The provocation test was developed by a systemic administration of α-methyl-p-tyrosine (αMpT), a reversible inhibitor of tyrosine hydroxylase to MPTP-treated mice at the presymptomatic stage of parkinsonism. For this, we first selected a minimum dose of αMpT, which caused a decrease of the dopamine level in the striatum of normal mice below the threshold at which motor dysfunctions appear. Then, we found the maximum dose of αMpT at which a loss of dopamine in the striatum of normal mice did not reach the threshold level, and motor behavior was not impaired. We showed that αMpT at this dose induced a decrease of the dopamine concentration in the striatum of MPTP-treated mice at the presymptomatic stage of parkinsonism below a threshold level that results in the impairment of motor behavior. Finally, we proved that αMpT exerts a temporal and reversible influence on the nigrostriatal dopaminergic system of MPTP-treated mice with no long

Hostplant suitability and defensive chemistry of the Catalpa sphinx, Ceratomia catalpae.

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Bowers, M Deane

2003-10-01

The growth and survival of the Catalpa sphinx, Ceratomia catalpae (Sphingidae), were measured on five different species of Catalpa: C. bignonioides, C. bungeii, C. fargeseii, C. ovata, and C. speciosa. Larval growth varied significantly among these host plant species; however, survival did not differ. Quantification of the iridoid glycoside content of larvae, pupae, adults, larval frass, and leaves of the larval host plant, C. bignonioides, by gas chromatography showed that leaves contained both catalpol and catalposide; larvae, pupae, and frass contained only catalpol; and the adults contained no detectable iridoid glycosides. Amounts were highest in the larvae and declined in the pupal stage. Very small amounts of catalpol were detected in adults of the parasitoid, Cotesia congregata, and in the silken cocoons. The hemolymph in which the parasitoid larvae grew contained over 50% dry weight catalpol. Larvae of C. catalpae often regurgitate when disturbed. This may serve as a defense against predators. A comparison of the growth of larvae pinched with forceps to induce regurgitation with those that were not so treated showed that larvae that were pinched, and usually regurgitated, grew significantly more slowly than those that were not.

Sodium phenylbutyrate controls neuroinflammatory and antioxidant activities and protects dopaminergic neurons in mouse models of Parkinson's disease.

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Roy, Avik; Ghosh, Anamitra; Jana, Arundhati; Liu, Xiaojuan; Brahmachari, Saurav; Gendelman, Howard E; Pahan, Kalipada

2012-01-01

Neuroinflammation and oxidative stress underlie the pathogenesis of various neurodegenerative disorders. Here we demonstrate that sodium phenylbutyrate (NaPB), an FDA-approved therapy for reducing plasma ammonia and glutamine in urea cycle disorders, can suppress both proinflammatory molecules and reactive oxygen species (ROS) in activated glial cells. Interestingly, NaPB also decreased the level of cholesterol but involved only intermediates, not the end product of cholesterol biosynthesis pathway for these functions. While inhibitors of both geranylgeranyl transferase (GGTI) and farnesyl transferase (FTI) inhibited the activation of NF-κB, inhibitor of GGTI, but not FTI, suppressed the production of ROS. Accordingly, a dominant-negative mutant of p21(rac), but not p21(ras), attenuated the production of ROS from activated microglia. Inhibition of both p21(ras) and p21(rac) activation by NaPB in microglial cells suggests that NaPB exerts anti-inflammatory and antioxidative effects via inhibition of these small G proteins. Consistently, we found activation of both p21(ras) and p21(rac)in vivo in the substantia nigra of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Oral administration of NaPB reduced nigral activation of p21(ras) and p21(rac), protected nigral reduced glutathione, attenuated nigral activation of NF-κB, inhibited nigral expression of proinflammatory molecules, and suppressed nigral activation of glial cells. These findings paralleled dopaminergic neuronal protection, normalized striatal neurotransmitters, and improved motor functions in MPTP-intoxicated mice. Consistently, FTI and GGTI also protected nigrostriata in MPTP-intoxicated mice. Furthermore, NaPB also halted the disease progression in a chronic MPTP mouse model. These results identify novel mode of action of NaPB and suggest that NaPB may be of therapeutic benefit for neurodegenerative disorders.

Sodium phenylbutyrate controls neuroinflammatory and antioxidant activities and protects dopaminergic neurons in mouse models of Parkinson's disease.

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Avik Roy

Full Text Available Neuroinflammation and oxidative stress underlie the pathogenesis of various neurodegenerative disorders. Here we demonstrate that sodium phenylbutyrate (NaPB, an FDA-approved therapy for reducing plasma ammonia and glutamine in urea cycle disorders, can suppress both proinflammatory molecules and reactive oxygen species (ROS in activated glial cells. Interestingly, NaPB also decreased the level of cholesterol but involved only intermediates, not the end product of cholesterol biosynthesis pathway for these functions. While inhibitors of both geranylgeranyl transferase (GGTI and farnesyl transferase (FTI inhibited the activation of NF-κB, inhibitor of GGTI, but not FTI, suppressed the production of ROS. Accordingly, a dominant-negative mutant of p21(rac, but not p21(ras, attenuated the production of ROS from activated microglia. Inhibition of both p21(ras and p21(rac activation by NaPB in microglial cells suggests that NaPB exerts anti-inflammatory and antioxidative effects via inhibition of these small G proteins. Consistently, we found activation of both p21(ras and p21(racin vivo in the substantia nigra of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mouse model of Parkinson's disease. Oral administration of NaPB reduced nigral activation of p21(ras and p21(rac, protected nigral reduced glutathione, attenuated nigral activation of NF-κB, inhibited nigral expression of proinflammatory molecules, and suppressed nigral activation of glial cells. These findings paralleled dopaminergic neuronal protection, normalized striatal neurotransmitters, and improved motor functions in MPTP-intoxicated mice. Consistently, FTI and GGTI also protected nigrostriata in MPTP-intoxicated mice. Furthermore, NaPB also halted the disease progression in a chronic MPTP mouse model. These results identify novel mode of action of NaPB and suggest that NaPB may be of therapeutic benefit for neurodegenerative disorders.

Sodium Phenylbutyrate Controls Neuroinflammatory and Antioxidant Activities and Protects Dopaminergic Neurons in Mouse Models of Parkinson’s Disease

Science.gov (United States)

Jana, Arundhati; Liu, Xiaojuan; Brahmachari, Saurav; Gendelman, Howard E.; Pahan, Kalipada

2012-01-01

Neuroinflammation and oxidative stress underlie the pathogenesis of various neurodegenerative disorders. Here we demonstrate that sodium phenylbutyrate (NaPB), an FDA-approved therapy for reducing plasma ammonia and glutamine in urea cycle disorders, can suppress both proinflammatory molecules and reactive oxygen species (ROS) in activated glial cells. Interestingly, NaPB also decreased the level of cholesterol but involved only intermediates, not the end product of cholesterol biosynthesis pathway for these functions. While inhibitors of both geranylgeranyl transferase (GGTI) and farnesyl transferase (FTI) inhibited the activation of NF-κB, inhibitor of GGTI, but not FTI, suppressed the production of ROS. Accordingly, a dominant-negative mutant of p21rac, but not p21ras, attenuated the production of ROS from activated microglia. Inhibition of both p21ras and p21rac activation by NaPB in microglial cells suggests that NaPB exerts anti-inflammatory and antioxidative effects via inhibition of these small G proteins. Consistently, we found activation of both p21ras and p21rac in vivo in the substantia nigra of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. Oral administration of NaPB reduced nigral activation of p21ras and p21rac, protected nigral reduced glutathione, attenuated nigral activation of NF-κB, inhibited nigral expression of proinflammatory molecules, and suppressed nigral activation of glial cells. These findings paralleled dopaminergic neuronal protection, normalized striatal neurotransmitters, and improved motor functions in MPTP-intoxicated mice. Consistently, FTI and GGTI also protected nigrostriata in MPTP-intoxicated mice. Furthermore, NaPB also halted the disease progression in a chronic MPTP mouse model. These results identify novel mode of action of NaPB and suggest that NaPB may be of therapeutic benefit for neurodegenerative disorders. PMID:22723850

Lebetin 2, a Snake Venom-Derived Natriuretic Peptide, Attenuates Acute Myocardial Ischemic Injury through the Modulation of Mitochondrial Permeability Transition Pore at the Time of Reperfusion.

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Bochra Tourki

Full Text Available Cardiac ischemia is one of the leading causes of death worldwide. It is now well established that natriuretic peptides can attenuate the development of irreversible ischemic injury during myocardial infarction. Lebetin 2 (L2 is a new discovered peptide isolated from Macrovipera lebetina venom with structural similarity to B-type natriuretic peptide (BNP. Our objectives were to define the acute cardioprotective actions of L2 in isolated Langendorff-perfused rat hearts after regional or global ischemia-reperfusion (IR. We studied infarct size, left ventricular contractile recovery, survival protein kinases and mitochondrial permeability transition pore (mPTP opening in injured myocardium. L2 dosage was determined by preliminary experiments at its ability to induce cyclic guanosine monophosphate (cGMP release without changing hemodynamic effects in normoxic hearts. L2 was found to be as effective as BNP in reducing infarct size after the induction of either regional or global IR. Both peptides equally improved contractile recovery after regional IR, but only L2 increased coronary flow and reduced severe contractile dysfunction after global ischemia. Cardioprotection afforded by L2 was abolished after isatin or 5-hydroxydecanote pretreatment suggesting the involvement of natriuretic peptide receptors and mitochondrial KATP (mitoKATP channels in the L2-induced effects. L2 also increased survival protein expression in the reperfused myocardium as evidenced by phosphorylation of signaling pathways PKCε/ERK/GSK3β and PI3K/Akt/eNOS. IR induced mitochondrial pore opening, but this effect was markedly prevented by L2 treatment. These data show that L2 has strong cardioprotective effect in acute ischemia through stimulation of natriuretic peptide receptors. These beneficial effects are mediated, at least in part, by mitoKATP channel opening and downstream activated survival kinases, thus delaying mPTP opening and improving IR-induced mitochondrial

Involvement of PPAR-γ in the neuroprotective and anti-inflammatory effects of angiotensin type 1 receptor inhibition: effects of the receptor antagonist telmisartan and receptor deletion in a mouse MPTP model of Parkinson's disease

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Garrido-Gil Pablo

2012-02-01

Full Text Available Abstract Background Several recent studies have shown that angiotensin type 1 receptor (AT1 antagonists such as candesartan inhibit the microglial inflammatory response and dopaminergic cell loss in animal models of Parkinson's disease. However, the mechanisms involved in the neuroprotective and anti-inflammatory effects of AT1 blockers in the brain have not been clarified. A number of studies have reported that AT1 blockers activate peroxisome proliferator-activated receptor gamma (PPAR γ. PPAR-γ activation inhibits inflammation, and may be responsible for neuroprotective effects, independently of AT1 blocking actions. Methods We have investigated whether oral treatment with telmisartan (the most potent PPAR-γ activator among AT1 blockers provides neuroprotection against dopaminergic cell death and neuroinflammation, and the possible role of PPAR-γ activation in any such neuroprotection. We used a mouse model of parkinsonism induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP and co-administration of the PPAR-γ antagonist GW9662 to study the role of PPAR-γ activation. In addition, we used AT1a-null mice lesioned with MPTP to study whether deletion of AT1 in the absence of any pharmacological effect of AT1 blockers provides neuroprotection, and investigated whether PPAR-γ activation may also be involved in any such effect of AT1 deletion by co-administration of the PPAR-γ antagonist GW9662. Results We observed that telmisartan protects mouse dopaminergic neurons and inhibits the microglial response induced by administration of MPTP. The protective effects of telmisartan on dopaminergic cell death and microglial activation were inhibited by co-administration of GW9662. Dopaminergic cell death and microglial activation were significantly lower in AT1a-null mice treated with MPTP than in mice not subjected to AT1a deletion. Interestingly, the protective effects of AT1 deletion were also inhibited by co

Regional characterization of energy metabolism in the brain of normal and MPTP-intoxicated mice using new markers of glucose and phosphate transport

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Touhami Jawida

2010-12-01

Full Text Available Abstract The gibbon ape leukemia virus (GALV, the amphotropic murine leukemia virus (AMLV and the human T-cell leukemia virus (HTLV are retroviruses that specifically bind nutrient transporters with their envelope glycoproteins (Env when entering host cells. Here, we used tagged ligands derived from GALV, AMLV, and HTLV Env to monitor the distribution of their cognate receptors, the inorganic phosphate transporters PiT1 and PiT2, and the glucose transporter GLUT1, respectively, in basal conditions and after acute energy deficiency. For this purpose, we monitored changes in the distribution of PiT1, PiT2 and GLUT1 in the cerebellum, the frontal cortex, the corpus callosum, the striatum and the substantia nigra (SN of C57/BL6 mice after administration of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridinium (MPTP, a mitochondrial complex I inhibitor which induces neuronal degeneration in the striato-nigral network. The PiT1 ligand stained oligodendrocytes in the corpus callosum and showed a reticular pattern in the SN. The PiT2 ligand stained particularly the cerebellar Purkinje cells, while GLUT1 labelling was mainly observed throughout the cortex, basal ganglia and cerebellar gray matter. Interestingly, unlike GLUT1 and PiT2 distributions which did not appear to be modified by MPTP intoxication, PiT1 immunostaining seemed to be more extended in the SN. The plausible reasons for this change following acute energy stress are discussed. These new ligands therefore constitute new metabolic markers which should help to unravel cellular adaptations to a wide variety of normal and pathologic conditions and to determine the role of specific nutrient transporters in tissue homeostasis.

Neutral Sphingomyelinase Behaviour in Hippocampus Neuroinflammation of MPTP-Induced Mouse Model of Parkinson’s Disease and in Embryonic Hippocampal Cells

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Samuela Cataldi

2017-01-01

Full Text Available Neutral sphingomyelinase is known to be implicated in growth arrest, differentiation, proliferation, and apoptosis. Although previous studies have reported the involvement of neutral sphingomyelinase in hippocampus physiopathology, its behavior in the hippocampus during Parkinson’s disease remains undetected. In this study, we show an upregulation of inducible nitric oxide synthase and a downregulation of neutral sphingomyelinase in the hippocampus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP- induced mouse model of Parkinson’s disease. Moreover, the stimulation of neutral sphingomyelinase activity with vitamin 1,25-dihydroxyvitamin D3 reduces specifically saturated fatty acid sphingomyelin by making sphingomyelin a less rigid molecule that might influence neurite plasticity. The possible biological relevance of the increase of neutral sphingomyelinase in Parkinson’s disease is discussed.

Chronic levodopa administration followed by a washout period increased number and induced phenotypic changes in striatal dopaminergic cells in MPTP-monkeys.

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Carla DiCaudo

Full Text Available In addition to the medium spiny neurons the mammalian striatum contains a small population of GABAergic interneurons that are immunoreactive for tyrosine hydroxylase (TH, which dramatically increases after lesions to the nigrostriatal pathway and striatal delivery of neurotrophic factors. The regulatory effect of levodopa (L-Dopa on the number and phenotype of these cells is less well understood. Eleven macaques (Macaca fascicularis were included. Group I (n = 4 received 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP and L-Dopa; Group II (n = 4 was treated with MPTP plus vehicle and Group III (n = 3 consist of intact animals (control group. L-Dopa and vehicle were given for 1 year and animals sacrificed 6 months later. Immunohistochemistry against TH was used to identify striatal and nigral dopaminergic cells. Double and triple labeling immunofluorescence was performed to detect the neurochemical characteristics of the striatal TH-ir cells using antibodies against: TH, anti-glutamate decarboxylase (GAD(67 anti-calretinin (CR anti-dopa decarboxylase (DDC and anti-dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32. The greatest density of TH-ir striatal cells was detected in the striatum of the L-Dopa treated monkeys and particularly in its associative territory. None of the striatal TH-ir cell expressed DARPP-32 indicating they are interneurons. The percentages of TH-ir cells that expressed GAD67 and DDC was approximately 50%. Interestingly, we found that in the L-Dopa group the number of TH/CR expressing cells was significantly reduced. We conclude that chronic L-Dopa administration produced a long-lasting increase in the number of TH-ir cells, even after a washout period of 6 months. L-Dopa also modified the phenotype of these cells with a significant reduction of the TH/CR phenotype in favor of an increased number of TH/GAD cells that do not express CR. We suggest that the increased number of striatal TH-ir cells might be involved

Epigallocatechin gallate protects dopaminergic neurons against 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity by inhibiting microglial cell activation.

Science.gov (United States)

Li, Rui; Peng, Ning; Du, Fang; Li, Xu-ping; Le, Wei-dong

2006-04-01

To observe whether the dopaminergic neuroprotective effect of (-)-epigallocatechin gallate (EGCG) is associated with its inhibition of microglial cell activation in vivo. The effects of EGCG at different doses on dopaminergic neuronal survival were tested in a methyl-4-phenyl-pyridinium (MPP+)-induced dopaminergic neuronal injury model in the primary mesencephalic cell cultures. With unbiased stereological method, tyrosine hydroxylase-immunoreactive (TH-ir) cells were counted in the A8, A9 and A10 regions of the substantia nigra (SN) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57BL/6 mice. The effect of EGCG on microglial activation in the SN was also investigated. Pretreatment with EGCG (1 to 100 micromol/L) significantly attenuated MPP+-induced TH-ir cell loss by 22.2% to 80.5% in the mesencephalic cell cultures. In MPTP-treated C57BL/6 mice, EGCG at a low concentration (1 mg/kg) provided significant protection against MPTP-induced TH-ir cell loss by 50.9% in the whole nigral area and by 71.7% in the A9 region. EGCG at 5 mg/kg showed more prominent protective effect than at 1 or 10 mg/kg. EGCG pretreatment significantly inhibited microglial activation and CD11b expression induced by MPTP. EGCG exerts potent dopaminergic neuroprotective activity by means of microglial inhibition, which shed light on the potential use of EGCG in treatment of Parkinson's disease.

Unusual iridoid glycosides in Veronica sects. Hebe and Labiatoides

DEFF Research Database (Denmark)

Jensen, Søren Rosendal

2008-01-01

iridoids common to the genus. The chemical profile of V. perfoliata is similar to that of Northern hemisphere species of Veronica because of the presence of characteristic 6-O-catalpol esters. The profile of V. derwentiana is unique, since 6-O-esters of aucubin rather than of catalpol dominate, however......In a chemosystematic investigation of three Southern hemisphere species of Veronica, namely the Australian V. derwentiana Andrews and V. perfoliata R.Br. (formerly Derwentia species), and the New Zealand V. catarractae G. Forster (formerly a species of Parahebe), the water-soluble constituents were...

Effects of attenuation map accuracy on attenuation-corrected micro-SPECT images

NARCIS (Netherlands)

Wu, C.; Gratama van Andel, H.A.; Laverman, P.; Boerman, O.C.; Beekman, F.J.

2013-01-01

Background In single-photon emission computed tomography (SPECT), attenuation of photon flux in tissue affects quantitative accuracy of reconstructed images. Attenuation maps derived from X-ray computed tomography (CT) can be employed for attenuation correction. The attenuation coefficients as well

Targeted Modification of Mitochondrial ROS Production Converts High Glucose-Induced Cytotoxicity to Cytoprotection: Effects on Anesthetic Preconditioning.

Science.gov (United States)

Sedlic, Filip; Muravyeva, Maria Y; Sepac, Ana; Sedlic, Marija; Williams, Anna Marie; Yang, Meiying; Bai, Xiaowen; Bosnjak, Zeljko J

2017-01-01

Contradictory reports on the effects of diabetes and hyperglycemia on myocardial infarction range from cytotoxicity to cytoprotection. The study was designed to investigate acute effects of high glucose-driven changes in mitochondrial metabolism and osmolarity on adaptive mechanisms and resistance to oxidative stress of isolated rat cardiomyocytes. We examined the effects of high glucose on several parameters of mitochondrial bioenergetics, including changes in oxygen consumption, mitochondrial membrane potential, and NAD(P)H fluorometry. Effects of high glucose on the endogenous cytoprotective mechanisms elicited by anesthetic preconditioning (APC) and the mediators of cell injury were also tested. These experiments included real-time measurements of reactive oxygen species (ROS) production and mitochondrial permeability transition pore (mPTP) opening in single cells by laser scanning fluorescence confocal microscopy, and cell survival assay. High glucose rapidly enhanced mitochondrial energy metabolism, observed by increase in NAD(P)H fluorescence intensity, oxygen consumption, and mitochondrial membrane potential. This substantially elevated production of ROS, accelerated opening of the mPTP, and decreased survival of cells exposed to oxidative stress. Abrogation of high glucose-induced mitochondrial hyperpolarization with 2,4 dinitrophenol (DNP) significantly, but not completely, attenuated ROS production to a level similar to hyperosmotic mannitol control. DNP treatment reversed high glucose-induced cytotoxicity to cytoprotection. Hyperosmotic mannitol treatment also induced cytoprotection. High glucose abrogated APC-induced mitochondrial depolarization, delay in mPTP opening and cytoprotection. In conclusion, high glucose-induced mitochondrial hyperpolarization abolishes APC and augments cell injury. Attenuation of high glucose-induced ROS production by eliminating mitochondrial hyperpolarization protects cardiomyocytes. J. Cell. Physiol. 232: 216-224, 2017

Do fungivores trigger the transfer of protective metabolites from host plants to arbuscular mycorrhizal hyphae?

Science.gov (United States)

Duhamel, Marie; Pel, Roel; Ooms, Astra; Bücking, Heike; Jansa, Jan; Ellers, Jacintha; van Straalen, Nico M; Wouda, Tjalf; Vandenkoornhuyse, Philippe; Kiers, E Toby

2013-09-01

A key objective in ecology is to understand how cooperative strategies evolve and are maintained in species networks. Here, we focus on the tri-trophic relationship between arbuscular mycorrhizal (AM) fungi, host plants, and fungivores to ask if host plants are able to protect their mutualistic mycorrhizal partners from being grazed. Specifically, we test whether secondary metabolites are transferred from hosts to fungal partners to increase their defense against fungivores. We grew Plantago lanceolata hosts with and without mycorrhizal inoculum, and in the presence or absence of fungivorous springtails. We then measured fungivore effects on host biomass and mycorrhizal abundance (using quantitative PCR) in roots and soil. We used high-performance liquid chromatography to measure host metabolites in roots, shoots, and hyphae, focusing on catalpol, aucubin, and verbascoside. Our most striking result was that the metabolite catalpol was consistently found in AM fungal hyphae in host plants exposed to fungivores. When fungivores were absent, catalpol was undetectable in hyphae. Our results highlight the potential for plant-mediated protection of the mycorrhizal hyphal network.

SOCIAL BEHAVIORAL CHANGES IN MPTP-TREATED MONKEY MODEL OF PARKINSON’S DISEASE.

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Elodie eDURAND

2015-02-01

Full Text Available Parkinsonian patients experience not only the physical discomfort of motor disorders but also the considerable psychological distress caused by cognitive deficits and behavioral disorders. These two factors can result in a disruption of social relationships during the symptomatic and even the presymptomatic motor states of the disease. However, it remains difficult, if not impossible, to evaluate social relationships in presymptomatic patients. The present study focused on the evaluation of social relationships within a group of female long-tailed macaques during presymptomatic and symptomatic motor states induced by Chronic Low-Dose (CLD and then Chronic High-Dose (CHD systemic administration of 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP. Dopaminergic denervation within basal ganglia and cortical areas was evaluated using Positron Emission Tomography (PET scans with 18F-DOPA (6-[18F]-fluoro-L-3,4-dihydroxyphenylalanine radiotracer.Interestingly, social behavioral changes could be identified in the presymptomatic motor state before any motor and/or cognitive impairment occurred. Stronger effects were observed in subordinate animals compared to dominant animals. From baseline state to CLD-presymptomatic motor state, the frequency of emitted affiliative and aggressive behaviors increased. From CLD-presymptomatic to CHD-presymptomatic motor states, the frequency of the three categories of social behaviors (aggressive, submissive and affiliative decreased. At this time, quantitative data analysis in PET scans highlighted a dopaminergic denervation in the insula and the posterior caudate nucleus. Finally, the frequency of the three categories of social behaviors decreased during the stable-symptomatic motor state compared to baseline and presymptomatic motor states; this was also associated with motor and cognitive disorders and a dopaminergic denervation in all the evaluated cortical and subcortical structures.

Control algorithms for dynamic attenuators

Energy Technology Data Exchange (ETDEWEB)

Hsieh, Scott S., E-mail: sshsieh@stanford.edu [Department of Radiology, Stanford University, Stanford, California 94305 and Department of Electrical Engineering, Stanford University, Stanford, California 94305 (United States); Pelc, Norbert J. [Department of Radiology, Stanford University, Stanford California 94305 and Department of Bioengineering, Stanford University, Stanford, California 94305 (United States)

2014-06-15

Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not requirea priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

Control algorithms for dynamic attenuators

International Nuclear Information System (INIS)

Hsieh, Scott S.; Pelc, Norbert J.

2014-01-01

Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not requirea priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

Control algorithms for dynamic attenuators.

Science.gov (United States)

Hsieh, Scott S; Pelc, Norbert J

2014-06-01

The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not require a priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current modulation) without

Magnetic resonance imaging and tensor-based morphometry in the MPTP non-human primate model of Parkinson's disease.

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Michel Modo

Full Text Available Parkinson's disease (PD is the second most common neurodegenerative disorder producing a variety of motor and cognitive deficits with the causes remaining largely unknown. The gradual loss of the nigrostriatal pathway is currently considered the pivotal pathological event. To better understand the progression of PD and improve treatment management, defining the disease on a structural basis and expanding brain analysis to extra-nigral structures is indispensable. The anatomical complexity and the presence of neuromelanin, make the use of non-human primates an essential element in developing putative imaging biomarkers of PD. To this end, ex vivo T2-weighted magnetic resonance images were acquired from control and 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP-treated marmosets. Volume measurements of the caudate, putamen, and substantia nigra indicated significant atrophy and cortical thinning. Tensor-based morphometry provided a more extensive and hypothesis free assessment of widespread changes caused by the toxin insult to the brain, especially highlighting regional cortical atrophy. The results highlight the importance of developing imaging biomarkers of PD in non-human primate models considering their distinct neuroanatomy. It is essential to further develop these biomarkers in vivo to provide non-invasive tools to detect pre-symptomatic PD and to monitor potential disease altering therapeutics.

Magnetic resonance imaging and tensor-based morphometry in the MPTP non-human primate model of Parkinson's disease.

Science.gov (United States)

Modo, Michel; Crum, William R; Gerwig, Madeline; Vernon, Anthony C; Patel, Priya; Jackson, Michael J; Rose, Sarah; Jenner, Peter; Iravani, Mahmoud M

2017-01-01

Parkinson's disease (PD) is the second most common neurodegenerative disorder producing a variety of motor and cognitive deficits with the causes remaining largely unknown. The gradual loss of the nigrostriatal pathway is currently considered the pivotal pathological event. To better understand the progression of PD and improve treatment management, defining the disease on a structural basis and expanding brain analysis to extra-nigral structures is indispensable. The anatomical complexity and the presence of neuromelanin, make the use of non-human primates an essential element in developing putative imaging biomarkers of PD. To this end, ex vivo T2-weighted magnetic resonance images were acquired from control and 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmosets. Volume measurements of the caudate, putamen, and substantia nigra indicated significant atrophy and cortical thinning. Tensor-based morphometry provided a more extensive and hypothesis free assessment of widespread changes caused by the toxin insult to the brain, especially highlighting regional cortical atrophy. The results highlight the importance of developing imaging biomarkers of PD in non-human primate models considering their distinct neuroanatomy. It is essential to further develop these biomarkers in vivo to provide non-invasive tools to detect pre-symptomatic PD and to monitor potential disease altering therapeutics.

Photon attenuation by intensifying screens

International Nuclear Information System (INIS)

Holje, G.

1983-01-01

The photon attenuation by intensifying screens of different chemical composition has been determined. The attenuation of photons between 20 keV and 120 keV was measured by use of a multi-channel analyzer and a broad bremsstrahlung distribution. The attenuation by the intensifying screens was hereby determined simultaneously at many different monoenergetic photon energies. Experimentally determined attenuations were found to agree well with attenuation calculated from mass attenuation coefficients. The attenuation by the screens was also determined at various bremsstrahlung distributions, simulating those occurring behind the patient in various diagnostic X-ray examinations. The high attenuation in some of the intensifying screens form the basis for an analysis of the construction of asymmetric screen pairs. Single screen systems are suggested as a favourable alternative to thick screen pair systems. (Author)

Tracer attenuation in groundwater

Science.gov (United States)

Cvetkovic, Vladimir

2011-12-01

The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

Gastrodin Protects Apoptotic Dopaminergic Neurons in a Toxin-Induced Parkinson’s Disease Model

Directory of Open Access Journals (Sweden)

Hemant Kumar

2013-01-01

Full Text Available Gastrodia elata (GE Blume is one of the most important traditional plants in Oriental countries and has been used for centuries to improve various conditions. The phenolic glucoside gastrodin is an active constituent of GE. The aim of this study was to investigate the neuroprotective role of gastrodin in 1-methyl-4-phenylpyridinium (MPP+/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP induced human dopaminergic SH-SY5Y cells and mouse model of Parkinson’s disease (PD, respectively. Gastrodin significantly and dose dependently protected dopaminergic neurons against neurotoxicity through regulating free radicals, Bax/Bcl-2 mRNA, caspase-3, and cleaved poly(ADP-ribose polymerase (PARP in SH-SY5Y cells stressed with MPP+. Gastrodin also showed neuroprotective effects in the subchronic MPTP mouse PD model by ameliorating bradykinesia and motor impairment in the pole and rotarod tests, respectively. Consistent with this finding, gastrodin prevented dopamine depletion and reduced reactive astrogliosis caused by MPTP as assessed by immunohistochemistry and immunoblotting in the substantiae nigrae and striatata of mice. Moreover, gastrodin was also effective in preventing neuronal apoptosis by attenuating antioxidant and antiapoptotic activities in these brain areas. These results strongly suggest that gastrodin has protective effects in experimental PD models and that it may be developed as a clinical candidate to ameliorate PD symptoms.

Magnetic resonance imaging and tensor-based morphometry in the MPTP non-human primate model of Parkinson’s disease

Science.gov (United States)

Crum, William R.; Gerwig, Madeline; Vernon, Anthony C.; Patel, Priya; Jackson, Michael J.; Rose, Sarah; Jenner, Peter; Iravani, Mahmoud M.

2017-01-01

Parkinson’s disease (PD) is the second most common neurodegenerative disorder producing a variety of motor and cognitive deficits with the causes remaining largely unknown. The gradual loss of the nigrostriatal pathway is currently considered the pivotal pathological event. To better understand the progression of PD and improve treatment management, defining the disease on a structural basis and expanding brain analysis to extra-nigral structures is indispensable. The anatomical complexity and the presence of neuromelanin, make the use of non-human primates an essential element in developing putative imaging biomarkers of PD. To this end, ex vivo T2-weighted magnetic resonance images were acquired from control and 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmosets. Volume measurements of the caudate, putamen, and substantia nigra indicated significant atrophy and cortical thinning. Tensor-based morphometry provided a more extensive and hypothesis free assessment of widespread changes caused by the toxin insult to the brain, especially highlighting regional cortical atrophy. The results highlight the importance of developing imaging biomarkers of PD in non-human primate models considering their distinct neuroanatomy. It is essential to further develop these biomarkers in vivo to provide non-invasive tools to detect pre-symptomatic PD and to monitor potential disease altering therapeutics. PMID:28738061

Gain attenuation of gated framing camera

International Nuclear Information System (INIS)

Xiao Shali; Liu Shenye; Cao Zhurong; Li Hang; Zhang Haiying; Yuan Zheng; Wang Liwei

2009-01-01

The theoretic model of framing camera's gain attenuation is analyzed. The exponential attenuation curve of the gain along the pulse propagation time is simulated. An experiment to measure the coefficient of gain attenuation based on the gain attenuation theory is designed. Experiment result shows that the gain follows an exponential attenuation rule with a quotient of 0.0249 nm -1 , the attenuation coefficient of the pulse is 0.00356 mm -1 . The loss of the pulse propagation along the MCP stripline is the leading reason of gain attenuation. But in the figure of a single stripline, the gain dose not follow the rule of exponential attenuation completely, instead, there is a gain increase at the stripline bottom. That is caused by the reflection of the pulse. The reflectance is about 24.2%. Combining the experiment and theory, which design of the stripline MCP can improved the gain attenuation. (authors)

Attenuation correction for SPECT

International Nuclear Information System (INIS)

Hosoba, Minoru

1986-01-01

Attenuation correction is required for the reconstruction of a quantitative SPECT image. A new method for detecting body contours, which are important for the correction of tissue attenuation, is presented. The effect of body contours, detected by the newly developed method, on the reconstructed images was evaluated using various techniques for attenuation correction. The count rates in the specified region of interest in the phantom image by the Radial Post Correction (RPC) method, the Weighted Back Projection (WBP) method, Chang's method were strongly affected by the accuracy of the contours, as compared to those by Sorenson's method. To evaluate the effect of non-uniform attenuators on the cardiac SPECT, computer simulation experiments were performed using two types of models, the uniform attenuator model (UAM) and the non-uniform attenuator model (NUAM). The RPC method showed the lowest relative percent error (%ERROR) in UAM (11 %). However, 20 to 30 percent increase in %ERROR was observed for NUAM reconstructed with the RPC, WBP, and Chang's methods. Introducing an average attenuation coefficient (0.12/cm for Tc-99m and 0.14/cm for Tl-201) in the RPC method decreased %ERROR to the levels for UAM. Finally, a comparison between images, which were obtained by 180 deg and 360 deg scans and reconstructed from the RPC method, showed that the degree of the distortion of the contour of the simulated ventricles in the 180 deg scan was 15 % higher than that in the 360 deg scan. (Namekawa, K.)

Improvement of quantitation in SPECT: Attenuation and scatter correction using non-uniform attenuation data

International Nuclear Information System (INIS)

Mukai, T.; Torizuka, K.; Douglass, K.H.; Wagner, H.N.

1985-01-01

Quantitative assessment of tracer distribution with single photon emission computed tomography (SPECT) is difficult because of attenuation and scattering of gamma rays within the object. A method considering the source geometry was developed, and effects of attenuation and scatter on SPECT quantitation were studied using phantoms with non-uniform attenuation. The distribution of attenuation coefficients (μ) within the source were obtained by transmission CT. The attenuation correction was performed by an iterative reprojection technique. The scatter correction was done by convolution of the attenuation corrected image and an appropriate filter made by line source studies. The filter characteristics depended on μ and SPEC measurement at each pixel. The SPECT obtained by this method showed the most reasonable results than the images reconstructed by other methods. The scatter correction could compensate completely for a 28% scatter components from a long line source, and a 61% component for thick and extended source. Consideration of source geometries was necessary for effective corrections. The present method is expected to be valuable for the quantitative assessment of regional tracer activity

mTOR inhibition sensitizes human hepatocellular carcinoma cells to resminostat

Energy Technology Data Exchange (ETDEWEB)

Peng, Xingang, E-mail: pengxinggang26@sina.com [Department of Emergency General Surgery, The Affiliated Hospital of Qingdao University, Qingdao (China); Zhang, Donghui, E-mail: zhangdonghuiyx@sina.com [Department of Infectious Disease, Linyi People’s Hospital, Linyi (China); Li, Zhengling, E-mail: lizhenglingzz@sina.com [Department of Nursing, Tengzhou Central People’s Hospital, Tengzhou (China); Fu, Meili, E-mail: fumeilidrlinyi@tom.com [Department of Infectious Disease, Linyi People’s Hospital, Linyi (China); Liu, Haiyan, E-mail: liuhaiyanlinyi5@sina.com [Department of Nursing, Linyi People’s Hospital, Linyi (China)

2016-09-02

Histone deacetylases (HDACs) hyper-activity in hepatocellular carcinoma (HCC) is often associated with patients’ poor prognosis. Our previous study has shown that resminostat, a novel HDAC inhibitor (HDACi), activated mitochondrial permeability transition pore (mPTP)-dependent apoptosis pathway in HCC cells. Here we explored the potential resminostat resistance factor by focusing on mammalian target of rapamycin (mTOR). We showed that AZD-2014, a novel mTOR kinase inhibitor, potentiated resminostat-induced cytotoxicity and proliferation inhibition in HCC cells. Molecularly, AZD-2014 enhanced resminostat-induced mPTP apoptosis pathway activation in HCC cells. Inhibition of this apoptosis pathway, by the caspase-9 specific inhibitor Ac-LEHD-CHO, the mPTP blockers (sanglifehrin A/cyclosporine A), or by shRNA-mediated knockdown of mPTP component cyclophilin-D (Cyp-D), significantly attenuated resminostat plus AZD-2014-induced cytotoxicity and apoptosis in HCC cells. Significantly, mTOR shRNA knockdown or kinase-dead mutation (Asp-2338-Ala) also sensitized HCC cells to resminostat, causing profound cytotoxicity and apoptosis induction. Together, these results suggest that mTOR could be a primary resistance factor of resminostat. Targeted inhibition of mTOR may thus significantly sensitize HCC cells to resminostat. - Highlights: • AZD-2014 potentiates resminostat’s cytotoxicity against HCC cells. • AZD-2014 facilitates resminostat-induced HCC cell apoptosis. • AZD-2014 augments resminostat-induced mitochondrial apoptosis pathway activation. • mTOR shRNA or kinase-dead mutation significantly sensitizes HCC cells to resminostat.

Neuroprotective Role of Atractylenolide-I in an In Vitro and In Vivo Model of Parkinson’s Disease

Directory of Open Access Journals (Sweden)

Sandeep More

2017-05-01

Full Text Available Parkinson’s disease (PD is an age-related neurological disorder characterized by a loss of dopaminergic neurons within the midbrain. Neuroinflammation has been nominated as one of the key pathogenic features of PD. Recently, the inadequate pharmacotherapy and adverse effects of conventional drugs have spurred the development of unconventional medications in the treatment of PD. The purpose of this study is to investigate the anti-neuroinflammatory mechanisms of Atractylenolide-I (ATR-I in in vivo and in vitro models of PD. Nitrite assay was measured via Griess reaction in lipopolysaccharide (LPS stimulated BV-2 cells. mRNA and protein levels were determined by a reverse transcription-polymerase chain reaction (RT-PCR and immunoblot analysis, respectively. Further, flow cytometry, immunocytochemistry, and immunohistochemistry were employed in BV-2 cells and MPTP-intoxicated C57BL6/J mice. Pre-treatment with ATR-I attenuated the inflammatory response in BV-2 cells by abating the nuclear translocation of nuclear factor-κB (NF-κB and by inducing heme oxygenase-1 (HO-1. The intraperitoneal administration of ATR-I reversed MPTP-induced behavioral deficits, decreased microglial activation, and conferred protection to dopaminergic neurons in the mouse model of PD. Our experimental reports establish the involvement of multiple benevolent molecular events by ATR-I in MPTP-induced toxicity, which may aid in the development of ATR-I as a new therapeutic agent for the treatment of PD.

Activation of mPTP-dependent mitochondrial apoptosis pathway by a novel pan HDAC inhibitor resminostat in hepatocellular carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Fu, Meili [Department of Infectious Disease, Linyi People’s Hospital, Linyi (China); Shi, Wenhong [Department of Radiotherapy, Linyi Tumor Hospital, Linyi (China); Li, Zhengling [Department of Nursing, Tengzhou Central People’s Hospital, Tengzhou (China); Liu, Haiyan, E-mail: liuhaiyanlinyi5@sina.com [Department of Nursing, Linyi People’s Hospital, No. 27 Jiefang Road, Linyi 276000, Shandong (China)

2016-09-02

Over-expression and aberrant activation of histone deacetylases (HDACs) are often associated with poor prognosis of hepatocellular carcinoma (HCC). Here, we evaluated the potential anti-hepatocellular carcinoma (HCC) cell activity by resminostat, a novel pan HDAC inhibitor (HDACi). We demonstrated that resminostat induced potent cytotoxic and anti-proliferative activity against established HCC cell lines (HepG2, HepB3, SMMC-7721) and patient-derived primary HCC cells. Further, resminostat treatment in HCC cells activated mitochondrial permeability transition pore (mPTP)-dependent apoptosis pathway, which was evidenced by physical association of cyclophilin-D and adenine nucleotide translocator 1 (ANT-1), mitochondrial depolarization, cytochrome C release and caspase-9 activation. Intriguingly, the mPTP blockers (sanglifehrin A and cyclosporine A), shRNA knockdown of cyclophilin-D or the caspase-9 inhibitor dramatically attenuated resminostat-induced HCC cell apoptosis and cytotoxicity. Reversely, HCC cells with exogenous cyclophilin-D over-expression were hyper-sensitive to resminostat. Intriguingly, a low concentration of resminostat remarkably potentiated sorafenib-induced mitochondrial apoptosis pathway activation, leading to a profound cytotoxicity in HCC cells. The results of this preclinical study indicate that resminostat (or plus sorafenib) could be further investigated as a valuable anti-HCC strategy. - Highlights: • Resminostat inhibits human HCC cell survival and proliferation. • Resminostat activates mPTP-dependent mitochondrial apoptosis pathway in HCC cells. • Resminostat potentiates sorafenib-induced mitochondrial apoptosis pathway activation. • mPTP or caspase-9 inhibition attenuates apoptosis by resminostat or plus sorafenib.

Landing gear noise attenuation

Science.gov (United States)

Moe, Jeffrey W. (Inventor); Whitmire, Julia (Inventor); Kwan, Hwa-Wan (Inventor); Abeysinghe, Amal (Inventor)

2011-01-01

A landing gear noise attenuator mitigates noise generated by airframe deployable landing gear. The noise attenuator can have a first position when the landing gear is in its deployed or down position, and a second position when the landing gear is in its up or stowed position. The noise attenuator may be an inflatable fairing that does not compromise limited space constraints associated with landing gear retraction and stowage. A truck fairing mounted under a truck beam can have a compliant edge to allow for non-destructive impingement of a deflected fire during certain conditions.

Inorganic polyphosphate (polyP) as an activator and structural component of the mitochondrial permeability transition pore.

Science.gov (United States)

Solesio, Maria E; Elustondo, Pia A; Zakharian, Eleonora; Pavlov, Evgeny V

2016-02-01

Mitochondrial permeability transition pore (mPTP) is a large channel located in the mitochondrial inner membrane. The opening of mPTP during pathological calcium overload leads to the membrane depolarization and disruption of ATP production. mPTP activation has been implicated as a central event during the process of stress-induced cell death. mPTP is a supramolecular complex composed of many proteins. Recent studies suggest that mitochondrial ATPase plays the central role in the formation of mPTP. However, the structure of the central conducting pore part of mPTP (mPTPore) remains elusive. Here we review current models proposed for the mPTPore and involvement of polyP in its formation and regulation. We discuss the underestimated role of polyP as an effector and a putative structural component of the mPTPore. We propose the hypothesis that inclusion of polyP can explain such properties of mPTP activity as calcium activation, selectivity and voltage-dependence. © 2016 Authors; published by Portland Press Limited.

MRI-guided attenuation correction in whole-body PET/MR. Assessment of the effect of bone attenuation

International Nuclear Information System (INIS)

Akbarzadeh, A.; Ay, M.R.; Ahmadian, A.; Riahi Alam, N.; Zaidi, H.

2013-01-01

Hybrid positron emission tomography (PET)/MRI presents many advantages in comparison with its counterpart PET/CT in terms of improved soft-tissue contrast, decrease in radiation exposure, and truly simultaneous and multi-parametric imaging capabilities. However, the lack of well-established methodology for MR-based attenuation correction is hampering further development and wider acceptance of this technology. We assess the impact of ignoring bone attenuation and using different tissue classes for generation of the attenuation map on the accuracy of attenuation correction of PET data. This work was performed using simulation studies based on the XCAT phantom and clinical input data. For the latter, PET and CT images of patients were used as input for the analytic simulation model using realistic activity distributions where CT-based attenuation correction was utilized as reference for comparison. For both phantom and clinical studies, the reference attenuation map was classified into various numbers of tissue classes to produce three (air, soft tissue and lung), four (air, lungs, soft tissue and cortical bones) and five (air, lungs, soft tissue, cortical bones and spongeous bones) class attenuation maps. The phantom studies demonstrated that ignoring bone increases the relative error by up to 6.8% in the body and up to 31.0% for bony regions. Likewise, the simulated clinical studies showed that the mean relative error reached 15% for lesions located in the body and 30.7% for lesions located in bones, when neglecting bones. These results demonstrate an underestimation of about 30% of tracer uptake when neglecting bone, which in turn imposes substantial loss of quantitative accuracy for PET images produced by hybrid PET/MRI systems. Considering bones in the attenuation map will considerably improve the accuracy of MR-guided attenuation correction in hybrid PET/MR to enable quantitative PET imaging on hybrid PET/MR technologies. (author)

The Role of Sulfur Dioxide in the Regulation of Mitochondrion-Related Cardiomyocyte Apoptosis in Rats with Isopropylarterenol-Induced Myocardial Injury

Directory of Open Access Journals (Sweden)

Junbao Du

2013-05-01

Full Text Available The authors investigated the regulatory effects of sulfur dioxide (SO2 on myocardial injury induced by isopropylarterenol (ISO hydrochloride and its mechanisms. Wistar rats were divided into four groups: control group, ISO group, ISO plus SO2 group, and SO2 only group. Cardiac function was measured and cardiomyocyte apoptosis was detected. Bcl-2, bax and cytochrome c (cytc expressions, and caspase-9 and caspase-3 activities in the left ventricular tissues were examined in the rats. The opening status of myocardial mitochondrial permeability transition pore (MPTP and membrane potential were analyzed. The results showed that ISO-treated rats developed heart dysfunction and cardiac injury. Furthermore, cardiomyocyte apoptosis in the left ventricular tissues was augmented, left ventricular tissue bcl-2 expression was down-regulated, bax expression was up-regulated, mitochondrial membrane potential was significantly reduced, MPTP opened, cytc release from mitochondrion into cytoplasm was significantly increased, and both caspase-9 and caspase-3 activities were increased. Administration of an SO2 donor, however, markedly improved heart function and relieved myocardial injury of the ISO-treated rats; it lessened cardiomyocyte apoptosis, up-regulated myocardial bcl-2, down-regulated bax expression, stimulated mitochondrial membrane potential, closed MPTP, and reduced cytc release as well as caspase-9 and caspase-3 activities in the left ventricular tissue. Hence, SO2 attenuated myocardial injury in association with the inhibition of apoptosis in myocardial tissues, and the bcl-2/cytc/caspase-9/caspase-3 pathway was possibly involved in this process.

4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to inhibit hepatocellular carcinoma cells

International Nuclear Information System (INIS)

Fu, Meili; Wan, Fuqiang; Li, Zhengling; Zhang, Fenghua

2016-01-01

The aim of the present study is to investigate the potential anti-hepatocellular carcinoma (HCC) cell activity by 4SC-202, a novel class I HDAC inhibitor (HDACi). The associated signaling mechanisms were also analyzed. We showed that 4SC-202 treatment induced potent cytotoxic and proliferation–inhibitory activities against established HCC cell lines (HepG2, HepB3, SMMC-7721) and patient-derived primary HCC cells. Further, adding 4SC-202 in HCC cells activated mitochondrial apoptosis pathway, which was evidenced by mitochondrial permeability transition pore (mPTP) opening, cytochrome C cytosol release and caspase-3/-9 activation. Inhibition of this apoptosis pathway, by caspase-3/-9 inhibitors, mPTP blockers, or by shRNA-mediated knockdown of cyclophilin-D (Cyp-D, a key component of mPTP), significantly attenuated 4SC-202-induced HCC cell death and apoptosis. Reversely, over-expression of Cyp-D enhanced 4SC-202's sensitivity in HCC cells. Further studies showed that 4SC-202 induced apoptosis signal-regulating kinase 1 (ASK1) activation, causing it translocation to mitochondria and physical association with Cyp-D. This mitochondrial ASK1-Cyp-D complexation appeared required for mediating 4SC-202-induced apoptosis activation. ASK1 stable knockdown by targeted-shRNAs largely inhibited 4SC-202-induced mPTP opening, cytochrome C release, and following HCC cell apoptotic death. Together, we suggest that 4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to potently inhibit human HCC cells. - Highlights: • 4SC-202 exerts potent anti-proliferative and cytotoxic activity against established/primary HCC cells. • SC-202-induced anti-HCC cell activity relies on caspase-dependent apoptosis activation. • 4SC-202 activates Cyp-D-dependent mitochondrial apoptosis pathway in HCC cells. • 4SC-202 activates ASK1 in HCC cells, causing it translocation to mitochondria. • Mitochondrial ASK1-Cyp-D complexation mediates 4SC-202's activity in HCC cells.

4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to inhibit hepatocellular carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Fu, Meili, E-mail: fumeilidrlinyi@tom.com [Department of Infectious Disease, Linyi People' s Hospital, Linyi 276000 (China); Wan, Fuqiang [Department of Head and Neck Surgery, Linyi Tumor Hospital, Linyi 276000 (China); Li, Zhengling [Department of Nursing, Tengzhou Central People' s Hospital, Tengzhou 277500 (China); Zhang, Fenghua [Department of Operating Room, Linyi People' s Hospital, Linyi 276000 (China)

2016-03-04

The aim of the present study is to investigate the potential anti-hepatocellular carcinoma (HCC) cell activity by 4SC-202, a novel class I HDAC inhibitor (HDACi). The associated signaling mechanisms were also analyzed. We showed that 4SC-202 treatment induced potent cytotoxic and proliferation–inhibitory activities against established HCC cell lines (HepG2, HepB3, SMMC-7721) and patient-derived primary HCC cells. Further, adding 4SC-202 in HCC cells activated mitochondrial apoptosis pathway, which was evidenced by mitochondrial permeability transition pore (mPTP) opening, cytochrome C cytosol release and caspase-3/-9 activation. Inhibition of this apoptosis pathway, by caspase-3/-9 inhibitors, mPTP blockers, or by shRNA-mediated knockdown of cyclophilin-D (Cyp-D, a key component of mPTP), significantly attenuated 4SC-202-induced HCC cell death and apoptosis. Reversely, over-expression of Cyp-D enhanced 4SC-202's sensitivity in HCC cells. Further studies showed that 4SC-202 induced apoptosis signal-regulating kinase 1 (ASK1) activation, causing it translocation to mitochondria and physical association with Cyp-D. This mitochondrial ASK1-Cyp-D complexation appeared required for mediating 4SC-202-induced apoptosis activation. ASK1 stable knockdown by targeted-shRNAs largely inhibited 4SC-202-induced mPTP opening, cytochrome C release, and following HCC cell apoptotic death. Together, we suggest that 4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to potently inhibit human HCC cells. - Highlights: • 4SC-202 exerts potent anti-proliferative and cytotoxic activity against established/primary HCC cells. • SC-202-induced anti-HCC cell activity relies on caspase-dependent apoptosis activation. • 4SC-202 activates Cyp-D-dependent mitochondrial apoptosis pathway in HCC cells. • 4SC-202 activates ASK1 in HCC cells, causing it translocation to mitochondria. • Mitochondrial ASK1-Cyp-D complexation mediates 4SC-202's activity in HCC cells.

PET attenuation coefficients from CT images: experimental evaluation of the transformation of CT into PET 511-keV attenuation coefficients.

Science.gov (United States)

Burger, C; Goerres, G; Schoenes, S; Buck, A; Lonn, A H R; Von Schulthess, G K

2002-07-01

The CT data acquired in combined PET/CT studies provide a fast and essentially noiseless source for the correction of photon attenuation in PET emission data. To this end, the CT values relating to attenuation of photons in the range of 40-140 keV must be transformed into linear attenuation coefficients at the PET energy of 511 keV. As attenuation depends on photon energy and the absorbing material, an accurate theoretical relation cannot be devised. The transformation implemented in the Discovery LS PET/CT scanner (GE Medical Systems, Milwaukee, Wis.) uses a bilinear function based on the attenuation of water and cortical bone at the CT and PET energies. The purpose of this study was to compare this transformation with experimental CT values and corresponding PET attenuation coefficients. In 14 patients, quantitative PET attenuation maps were calculated from germanium-68 transmission scans, and resolution-matched CT images were generated. A total of 114 volumes of interest were defined and the average PET attenuation coefficients and CT values measured. From the CT values the predicted PET attenuation coefficients were calculated using the bilinear transformation. When the transformation was based on the narrow-beam attenuation coefficient of water at 511 keV (0.096 cm(-1)), the predicted attenuation coefficients were higher in soft tissue than the measured values. This bias was reduced by replacing 0.096 cm(-1) in the transformation by the linear attenuation coefficient of 0.093 cm(-1) obtained from germanium-68 transmission scans. An analysis of the corrected emission activities shows that the resulting transformation is essentially equivalent to the transmission-based attenuation correction for human tissue. For non-human material, however, it may assign inaccurate attenuation coefficients which will also affect the correction in neighbouring tissue.

Measured attenuation correction methods

International Nuclear Information System (INIS)

Ostertag, H.; Kuebler, W.K.; Doll, J.; Lorenz, W.J.

1989-01-01

Accurate attenuation correction is a prerequisite for the determination of exact local radioactivity concentrations in positron emission tomography. Attenuation correction factors range from 4-5 in brain studies to 50-100 in whole body measurements. This report gives an overview of the different methods of determining the attenuation correction factors by transmission measurements using an external positron emitting source. The long-lived generator nuclide 68 Ge/ 68 Ga is commonly used for this purpose. The additional patient dose from the transmission source is usually a small fraction of the dose due to the subsequent emission measurement. Ring-shaped transmission sources as well as rotating point or line sources are employed in modern positron tomographs. By masking a rotating line or point source, random and scattered events in the transmission scans can be effectively suppressed. The problems of measured attenuation correction are discussed: Transmission/emission mismatch, random and scattered event contamination, counting statistics, transmission/emission scatter compensation, transmission scan after administration of activity to the patient. By using a double masking technique simultaneous emission and transmission scans become feasible. (orig.)

Attenuation coefficients of soils

International Nuclear Information System (INIS)

Martini, E.; Naziry, M.J.

1989-01-01

As a prerequisite to the interpretation of gamma-spectrometric in situ measurements of activity concentrations of soil radionuclides the attenuation of 60 to 1332 keV gamma radiation by soil samples varying in water content and density has been investigated. A useful empirical equation could be set up to describe the dependence of the mass attenuation coefficient upon photon energy for soil with a mean water content of 10%, with the results comparing well with data in the literature. The mean density of soil in the GDR was estimated at 1.6 g/cm 3 . This value was used to derive the linear attenuation coefficients, their range of variation being 10%. 7 figs., 5 tabs. (author)

Dopaol 2-keto- and 2,3-diketo-glycosides from Chelone obliqua (Scrophulariaceae)

DEFF Research Database (Denmark)

Franzyk, Henrik; Olsen, Carl Erik; Jensen, Søren Rosendal

2004-01-01

Two unique 2-(3,4-dihydroxyphenyl)ethyl glycosides, namely, dopaol beta-D-2-ketoglucopyranoside and dopaol beta-D-2,3-diketoglucopyranoside, were isolated from Chelone obliqua together with the iridoid glucoside catalpol, dopaol beta-D-glucopyranoside, descaffeoylverbascoside, and verbascoside. G...

Dopaol 2-keto- and 2,3-diketoglycosides from Chelone obliqua

DEFF Research Database (Denmark)

Franzyk, Henrik; Olsen, Carl Erik; Jensen, Søren Rosendal

2004-01-01

Two unique 2-(3,4-dihydroxyphenyl)ethyl glycosides, namely, dopaol beta-D-2-ketoglucopyranoside and dopaol beta-D-2,3-diketoglucopyranoside, were isolated from Chelone obliqua together with the iridoid glucoside catalpol, dopaol beta-D-glucopyranoside, descaffeoylverbascoside, and verbascoside. G...

A new phenylethanoid triglycoside in Veronica beccabunga L

DEFF Research Database (Denmark)

Jensen, Søren Rosendal; Opitz, Sebastian Ed. Wieland; Gotfredsen, Charlotte Held

2011-01-01

Besides the expected iridoid glucosides aucubin and catalpol as well as three known esters of the latter, Veronica beccabunga (brooklime) was shown to contain five carboxylated iridoid glucosides, namely gardoside, mussaenosidic acid, 8-epiloganic acid, arborescosidic acid and alpinoside. In addi...

Computer-controlled attenuator.

Science.gov (United States)

Mitov, D; Grozev, Z

1991-01-01

Various possibilities for applying electronic computer-controlled attenuators for the automation of physiological experiments are considered. A detailed description is given of the design of a 4-channel computer-controlled attenuator, in two of the channels of which the output signal can change by a linear step, in the other two channels--by a logarithmic step. This, together with the existence of additional programmable timers, allows to automate a wide range of studies in different spheres of physiology and psychophysics, including vision and hearing.

Ultrasound fields in an attenuating medium

DEFF Research Database (Denmark)

Jensen, Jørgen Arendt; Gandhi,, D; O'Brien,, W.D., Jr.

1993-01-01

of the rectangles and sums all contributions to arrive at the spatial impulse response for the aperture and field point. This approach makes it possible to model all transducer apertures, and the program can readily calculate the emitted, pulse-echo and continuous wave field. Attenuation is included by splitting...... it into a frequency dependent part and frequency independent part. The latter results in an attenuation factor that is multiplied onto the responses from the individual elements, and the frequency dependent part is handled by attenuating the basic one-dimensional pulse. The influence on ultrasound fields from......Ultrasound fields propagating in tissue will undergo changes in shape not only due to diffraction, but also due to the frequency dependent attenuation. Linear fields can be fairly well predicted for a non-attenuating medium like water by using the Tupholme-Stepanishen method for calculating...

Attenuation in Superconducting Circular Waveguides

Directory of Open Access Journals (Sweden)

K. H. Yeap

2016-09-01

Full Text Available We present an analysis on wave propagation in superconducting circular waveguides. In order to account for the presence of quasiparticles in the intragap states of a superconductor, we employ the characteristic equation derived from the extended Mattis-Bardeen theory to compute the values of the complex conductivity. To calculate the attenuation in a circular waveguide, the tangential fields at the boundary of the wall are first matched with the electrical properties (which includes the complex conductivity of the wall material. The matching of fields with the electrical properties results in a set of transcendental equations which is able to accurately describe the propagation constant of the fields. Our results show that although the attenuation in the superconducting waveguide above cutoff (but below the gap frequency is finite, it is considerably lower than that in a normal waveguide. Above the gap frequency, however, the attenuation in the superconducting waveguide increases sharply. The attenuation eventually surpasses that in a normal waveguide. As frequency increases above the gap frequency, Cooper pairs break into quasiparticles. Hence, we attribute the sharp rise in attenuation to the increase in random collision of the quasiparticles with the lattice structure.

Radiofrequency attenuator and method

Science.gov (United States)

Warner, Benjamin P [Los Alamos, NM; McCleskey, T Mark [Los Alamos, NM; Burrell, Anthony K [Los Alamos, NM; Agrawal, Anoop [Tucson, AZ; Hall, Simon B [Palmerston North, NZ

2009-01-20

Radiofrequency attenuator and method. The attenuator includes a pair of transparent windows. A chamber between the windows is filled with molten salt. Preferred molten salts include quarternary ammonium cations and fluorine-containing anions such as tetrafluoroborate (BF.sub.4.sup.-), hexafluorophosphate (PF.sub.6.sup.-), hexafluoroarsenate (AsF.sub.6.sup.-), trifluoromethylsulfonate (CF.sub.3SO.sub.3.sup.-), bis(trifluoromethylsulfonyl)imide ((CF.sub.3SO.sub.2).sub.2N.sup.-), bis(perfluoroethylsulfonyl)imide ((CF.sub.3CF.sub.2SO.sub.2).sub.2N.sup.-) and tris(trifluoromethylsulfonyl)methide ((CF.sub.3SO.sub.2).sub.3C.sup.-). Radicals or radical cations may be added to or electrochemically generated in the molten salt to enhance the RF attenuation.

Effect of Vitamin D in HN9.10e Embryonic Hippocampal Cells and in Hippocampus from MPTP-Induced Parkinson’s Disease Mouse Model

Directory of Open Access Journals (Sweden)

Samuela Cataldi

2018-02-01

Full Text Available It has long been proven that neurogenesis continues in the adult brains of mammals in the dentatus gyrus of the hippocampus due to the presence of neural stem cells. Although a large number of studies have been carried out to highlight the localization of vitamin D receptor in hippocampus, the expression of vitamin D receptor in neurogenic dentatus gyrus of hippocampus in Parkinson’s disease (PD and the molecular mechanisms triggered by vitamin D underlying the production of differentiated neurons from embryonic cells remain unknown. Thus, we performed a preclinical in vivo study by inducing PD in mice with MPTP and showed a reduction of glial fibrillary acidic protein (GFAP and vitamin D receptor in the dentatus gyrus of hippocampus. Then, we performed an in vitro study by inducing embryonic hippocampal cell differentiation with vitamin D. Interestingly, vitamin D stimulates the expression of its receptor. Vitamin D receptor is a transcription factor that probably is responsible for the upregulation of microtubule associated protein 2 and neurofilament heavy polypeptide genes. The latter increases heavy neurofilament protein expression, essential for neurofilament growth. Notably N-cadherin, implicated in activity for dendritic outgrowth, is upregulated by vitamin D.

Epigallocatechin Gallate Has a Neurorescue Effect in a Mouse Model of Parkinson Disease.

Science.gov (United States)

Xu, Qi; Langley, Monica; Kanthasamy, Anumantha G; Reddy, Manju B

2017-10-01

Background: Parkinson disease (PD) is a neurodegenerative disorder that has been associated with many factors, including oxidative stress, inflammation, and iron accumulation. The antioxidant, anti-inflammatory, and iron-chelating properties of epigallocatechin gallate (EGCG), a major polyphenol in green tea, may offer protection against PD. Objective: We sought to determine the neurorescue effects of EGCG and the role of iron in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. Methods: We evaluated the neurorescue effect of EGCG (25 mg/kg, 7 d, oral administration) against MPTP-induced (20 mg/kg, 3 d, intraperitoneal injection) neurodegeneration in C57 male black mice. Thirty mice weighing ∼25 g were divided into 3 groups: control, MPTP, and MPTP + EGCG. The neurorescue effect of EGCG was assessed with the use of motor behavior tests, neurotransmitter analysis, oxidative stress indicators, and iron-related protein expression. Results: Compared with the control group, MPTP treatment shortened the mice's latency to fall from the rotarod by 16% ( P < 0.05), decreased the striatal dopamine concentration by 58% ( P < 0.001) and dihydroxyphenylacetic acid by 35% ( P < 0.05), and increased serum protein carbonyls by 71% ( P = 0.07). However, EGCG rescued MPTP-induced neurotoxicity by increasing the rotational latency by 17% ( P < 0.05) to a value similar to the control group. Striatal dopamine concentrations were 40% higher in the MPTP + EGCG group than in the MPTP group ( P < 0.05), but the values were significantly lower than in the control group. Compared with the MPTP and control groups, mice in the MPTP + EGCG group had higher substantia nigra ferroportin expression (44% and 35%, respectively) ( P < 0.05) but not hepcidin and divalent metal transporter 1 expression. Conclusion: Overall, our study demonstrated that EGCG regulated the iron-export protein ferroportin in substantia nigra, reduced oxidative stress, and exerted a neurorescue effect

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine inhibits proton motive force in energized liver mitochondria

International Nuclear Information System (INIS)

Singh, Y.; Bhatnagar, R.; Sidhu, G.S.; Batra, J.K.; Krishna, G.

1989-01-01

It is known that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which induces Parkinson's-like disease in primates and humans, depletes hepatocytes of ATP and subsequently causes cell death. Incubation of rat liver mitochondria with MPTP and 1-methyl-4-phenyl pyridinium ion (MPP+) significantly inhibited incorporation of 32 Pi into ATP. MPTP and MPP+ inhibited the development of membrane potential and pH gradient in energized rat liver mitochondria, suggesting that reduction of the proton motive force may have reduced ATP synthesis. Since deprenyl, an inhibitor of monoamine oxidase, prevented the formation of MPP+ and inhibited the decrease in membrane potential caused by MPTP, but not that caused by MPP+, these effects of MPTP, as well as cell death, probably were mediated by MPP+. This mechanism may play a role in the specific loss of dopaminergic neurons resulting in MPTP-induced Parkinson's disease

The LCLS Gas Attenuator Revisited

International Nuclear Information System (INIS)

Ryutov, D

2005-01-01

In the report ''X-ray attenuation cell'' [1] a preliminary analysis of the gas attenuator for the Linac Coherent Light Source (LCLS) was presented. This analysis was carried out for extremely stringent set of specifications. In particular, a very large diameter for the unobstructed beam was set (1 cm) to accommodate the spontaneous radiation; the attenuator was supposed to cover the whole range of energies of the coherent radiation, from 800 eV to 8000 eV; the maximum attenuation was set at the level of 10 4 ; the use of solid attenuators was not allowed, as well as the use of rotating shutters. The need to reach a sufficient absorption at the high-energy end of the spectrum predetermined the choice of Xe as the working gas (in order to have a reasonable absorption at a not-too-high pressure). A sophisticated differential pumping system that included a Penning-type ion pump was suggested in order to minimize the gas leak into the undulator/accelerator part of the facility. A high cost of xenon meant also that an efficient (and expensive) gas-recovery system would have to be installed. The main parameter that determined the high cost and the complexity of the system was a large radius of the orifice. The present viewpoint allows for much smaller size of the orifice, r 0 = 1.5 mm. (1) The use of solid attenuators is also allowed (R.M. Bionta, private communication). It is, therefore, worthwhile to reconsider various parameters of the gas attenuator for these much less stringent conditions. This brief study should be considered as a physics input for the engineering design. As a working gas we consider now the argon, which, on the one hand, provides a reasonable absorption lengths and, on the other hand, is inexpensive enough to be exhausted into the atmosphere (no recovery). The absorption properties of argon are illustrated by Fig.1 where the attenuation factor A is shown for various beam energies, based on Ref. [2]. The other relevant parameters for argon are

Maximum likelihood estimation of the attenuated ultrasound pulse

DEFF Research Database (Denmark)

Rasmussen, Klaus Bolding

1994-01-01

The attenuated ultrasound pulse is divided into two parts: a stationary basic pulse and a nonstationary attenuation pulse. A standard ARMA model is used for the basic pulse, and a nonstandard ARMA model is derived for the attenuation pulse. The maximum likelihood estimator of the attenuated...

Inactivation of acetylcholinesterase by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride.

Science.gov (United States)

Zang, Lun-Yi; Misra, Hara P

2003-12-01

The neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to reversibly inhibit the activity of acetylcholinesterase. The inactivation of the enzyme was detected by monitoring the accumulation of yellow color produced from the reaction between thiocholine and dithiobisnitrobenzoate ion. The kinetic parameter, Km for the substrate (acetylthiocholine), was found to be 0.216 mM and Ki for MPTP inactivation of acetylcholinesterase was found to be 2.14 mM. The inactivation of enzyme by MPTP was found to be dose-dependent. It was found that MPTP is neither a substrate of AChE nor the time-dependent inactivator. The studies of reaction kinetics indicate the inactivation of AChE to be a linear mixed-type inhibition. The dilution assays indicate that MPTP is a reversible inhibitor for AChE. These data suggest that once MPTP enters the basal ganglia of the brain, it can inactivate the acetylcholinesterase enzyme and thereby increase the acetylcholine level in the basal ganglia of brain, leading to potential cell dysfunction. It appears that the nigrostriatal toxicity by MPTP leading to Parkinson's disease-like syndrome may, in part, be mediated via the acetylcholinesterase inactivation.

Entry of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into the rat brain

International Nuclear Information System (INIS)

Riachi, N.J.; LaManna, J.C.; Harik, S.I.

1989-01-01

We studied blood-to-brain entry of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridinium (MPP+) and butanol in anesthetized rats using the indicator-fractionation method with right atrial bolus injection. Minimal amounts of MPP+, which has low octanol/water partition coefficient, crossed the blood-brain barrier. MPTP and butanol, both of which have high octanol/water partition coefficients, were almost completely extracted by all regions of the brain on the first pass. The main difference between the MPTP and butanol tracers is that butanol rapidly left the brain with an exponential rate constant of 1.24 min-1, whereas MPTP was avidly retained by the brain with a washout rate constant of 0.10 min-1 (mean values for the four brain regions that we studied). Early retention of MPTP by the brain was not due to its rapid metabolism by monoamine oxidase because pargyline pretreatment did not affect this rate constant. However, 30 min after [ 3 H]MPTP injection, brain retention of the 3H tracer was reduced significantly by pargyline treatment, and the ratio of brain MPTP/MPP+ was increased markedly

Compensation for nonuniform attenuation in SPECT brain imaging

International Nuclear Information System (INIS)

Glick, S.J.; King, M.A.; Pan, T.S.; Soares, E.J.

1996-01-01

Accurate compensation for photon attenuation is needed to perform quantitative brain single-photon-emission computed tomographic (SPECT) imaging. Bellini's attenuation-compensation method has been used with a nonuniform attenuation map to account for the nonuniform attenuation properties of the head. Simulation studies using a three-dimensional (3-D) digitized anthropomorphic brain phantom were conducted to compare quantitative accuracy of reconstructions obtained with the nonuniform Bellini method to that obtained with the Chang method and to iterative reconstruction using maximum-likelihood expectation maximization (ML-EM). Using the Chang method and assuming the head to be a uniform attenuator gave reconstructions with an average bias of approximately 6-8%, whereas using the Bellini or the iterative ML-EM method with a nonuniform attenuation map gave an average bias of approximately 1%. The computation time required to implement nonuniform attenuation compensation with the Bellini algorithm is approximately equivalent to the time required to perform one iteration of ML-EM. Thus, using the Bellini method with a nonuniform attenuation map provides accurate compensation for photon attenuation within the head, and the method can be implemented in computation times suitable for routine clinical use

Attenuation of Vrancea events revisited

International Nuclear Information System (INIS)

Radulian, M.; Popa, M.; Grecu, B.; Panza, G.F.

2003-11-01

New aspects of the frequency-dependent attenuation of the seismic waves traveling from Vrancea subcrustal sources toward NW (Transylvanian Basin) and SE (Romanian Plain) are evidenced by the recent experimental data made available by the CALIXTO'99 tomography experiment. The observations validate the previous theoretical computations performed for the assessment, by means of a deterministic approach, of the seismic hazard in Romania. They reveal an essential aspect of the seismic ground motion attenuation, that has important implications on the probabilistic assessment of seismic hazard from Vrancea intermediate-depth earthquakes. The attenuation toward NW is shown to be a much stronger frequency-dependent effect than the attenuation toward SE and the seismic hazard computed by the deterministic approach fits satisfactorily well the observed ground motion distribution in the low-frequency band (< 1 Hz). The apparent contradiction with the historically-based intensity maps arises mainly from a systematic difference in the vulnerability (buildings eigenperiod) of the buildings in the intra- and extra-Carpathians regions. (author)

Determination of the attenuation map in emission tomography

CERN Document Server

Zaidi, H

2002-01-01

Reliable attenuation correction methods for quantitative emission computed tomography (ECT) require accurate delineation of the body contour and often necessitate knowledge of internal anatomical structure. Two broad classes of methods have been used to calculate the attenuation map referred to as "transmissionless" and transmission-based attenuation correction techniques. While calculated attenuation correction belonging to the first class of methods is appropriate for brain studies, more adequate methods must be performed in clinical applications where the attenuation coefficient distribution is not known a priori, and for areas of inhomogeneous attenuation such as the chest. Measured attenuation correction overcomes this problem and utilizes different approaches to determine this map including transmission scanning, segmented magnetic resonance images or appropriately scaled X-ray CT scans acquired either independently on separate or simultaneously on multimodality imaging systems. Combination of data acqu...

An acoustic eikonal equation for attenuating VTI media

KAUST Repository

Hao, Qi

2016-09-06

We present an acoustic eikonal equation governing the complex-valued travel time of P-waves in attenuating, transversely isotropic media with a vertical symmetry axis (VTI). This equation is based on the assumption that the Pwave complex-valued travel time is independent of the Swave velocity parameter v in Thomsen\\'s notation and the attenuation coefficient A in the Thomsen-type notation for attenuating VTI media. We combine perturbation theory and Shanks transform to develop practical approximations to the attenuating acoustic eikonal equation, capable of admitting analytical description of the attenuation in homogeneous media. For a horizontal, attenuating VTI layer, we also derive non-hyperbolic approximations for the real and imaginary parts of the complex-valued reflection travel time.

Ultrasonic attenuation in superconducting zinc

International Nuclear Information System (INIS)

Auluck, S.

1978-01-01

The differences in the Zn ultrasonic attenuation data of different workers are analyzed. The superconducting energy gaps deduced from our analysis of the ultrasonic-attenuation data of Cleavelin and Marshall are consistent with the gaps deduced from the knowledge of the Fermi surface and the electron-phonon mass enhancement factor

ENHANCEMENTS TO NATURAL ATTENUATION: SELECTED CASE STUDIES

Energy Technology Data Exchange (ETDEWEB)

Vangelas, K; W. H. Albright, W; E. S. Becvar, E; C. H. Benson, C; T. O. Early, T; E. Hood, E; P. M. Jardine, P; M. Lorah, M; E. Majche, E; D. Major, D; W. J. Waugh, W; G. Wein, G; O. R. West, O

2007-05-15

In 2003 the US Department of Energy (DOE) embarked on a project to explore an innovative approach to remediation of subsurface contaminant plumes that focused on introducing mechanisms for augmenting natural attenuation to achieve site closure. Termed enhanced attenuation (EA), this approach has drawn its inspiration from the concept of monitored natural attenuation (MNA).

Iridoid glucosides of Paederota bonarota and the relationships between Paederota and Veronica. II

DEFF Research Database (Denmark)

Jensen, Søren Rosendal; Gotfredsen, Charlotte Held; Pierce, Simon

2007-01-01

In a chemical investigation of the water soluble compounds in Paederota bonarota five known iridoid glucosides were isolated together with a compound with an 8,9-double bond, namely bonarotoside (10-O-benzoyl arborescosidic acid). The known iridoid glucosides were aucubin, catalpol and the 6-O-es...

Chemical Composition of Buddleja polystachya Aerial Parts and its Bioactivity against Aedes aegypti

Science.gov (United States)

A new acylatediridoid glycoside, 6-O-a-L-(2''-acetyl-4''-O-trans-isoferuloyl) rhamnopyranosyl catalpol (9) together with 18 known compounds belonging to the iridoids, flavonoids, triterpene saponin glycosides and phenylethanoids (1-8, 10-18) were isolated from the aerial parts and the flowers of Bud...

Self-attenuation factors in gamma-ray spectrometry

International Nuclear Information System (INIS)

Korun, M.

1999-01-01

The relation between the self-attenuation factors and the distribution function describing the number of photons detected in the full-energy peaks, as a function of their path length in the sample is presented. The relations between the self-attenuation factor and the moments of the distribution function, the average path length and the variance are also presented. The use of these relations is illustrated by applying them to self-attenuation factors describing attenuation in cylindrical samples. The results of the calculations are compared with the measured average path lengths and discussed in terms of the properties of the distribution function. (author)

Light attenuation in estuarine mangrove lakes

Science.gov (United States)

Frankovich, Thomas A.; Rudnick, David T.; Fourqurean, James W.

2017-01-01

Submerged aquatic vegetation (SAV) cover has declined in brackish lakes in the southern Everglades characterized by low water transparencies, emphasizing the need to evaluate the suitability of the aquatic medium for SAV growth and to identify the light attenuating components that contribute most to light attenuation. Underwater attenuation of downwards irradiance of photosynthetically active radiation (PAR) was determined over a three year period at 42 sites in shallow (freshwater flow into these areas may dilute CDOM concentrations and improve the salinity and light climate for SAV communities.

D-deprenyl protects nigrostriatal neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity.

Science.gov (United States)

Muralikrishnan, Dhanasekharan; Samantaray, Supriti; Mohanakumar, Kochupurackal P

2003-10-01

Selegiline (L-deprenyl) is believed to render protection against l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-neurotoxicity to a significant extent via a free radical scavenging mechanism, which is independent of its ability to inhibit monoamine oxidase-B (MAO-B) in the brain. We investigated the hydroxyl radical (.OH) scavenging action and neuroprotective effect of D-deprenyl, its less active isomer, in MPTP-induced dopaminergic neurotoxicity in mice to test whether the chemical structure of the molecule or its biological effects contribute to this property. To achieve this goal we studied the effects of D-deprenyl on: (1).OH production in a Fenton reaction; (2) MPTP-induced.OH generation and dopamine (DA) depletion in vivo, employing a sensitive HPLC-electrochemical procedure; and (3) formation of MPP(+) in vivo in the striatum following systemic administration of MPTP, employing an HPLC-photodiode array detection system. D-deprenyl inhibited ferrous citrate-induced.OH in vitro (0.45 microM) and MPTP-induced.OH in vivo in substantia nigra (SN) and in the striatum (1.0 mg/kg, i.p.). D-deprenyl did not, but L-deprenyl (0.5 mg/kg dose) did significantly inhibit formation of MPP(+) in the striatum 90 min following systemic MPTP injection. It failed to affect MAO-B activity at 0.5 mg/kg in the striatum, but effectively blocked MPTP-induced striatal DA depletion. The potency of D-deprenyl to scavenge MPTP-induced.OH in vivo and to render protection against the dopaminergic neurotoxicity without affecting dopamine turnover, MAO-B activity, or formation of MPP(+) in the brain indicates a direct involvement of.OH in the neurotoxic action of MPTP and antioxidant effect in the neuroprotective action of deprenyl. Copyright 2003 Wiley-Liss, Inc.

The path from mitochondrial ROS to aging runs through the mitochondrial permeability transition pore.

Science.gov (United States)

Rottenberg, Hagai; Hoek, Jan B

2017-10-01

Excessive production of mitochondrial reactive oxygen species (mROS) is strongly associated with mitochondrial and cellular oxidative damage, aging, and degenerative diseases. However, mROS also induces pathways of protection of mitochondria that slow aging, inhibit cell death, and increase lifespan. Recent studies show that the activation of the mitochondrial permeability transition pore (mPTP), which is triggered by mROS and mitochondrial calcium overloading, is enhanced in aged animals and humans and in aging-related degenerative diseases. mPTP opening initiates further production and release of mROS that damage both mitochondrial and nuclear DNA, proteins, and phospholipids, and also releases matrix NAD that is hydrolyzed in the intermembrane space, thus contributing to the depletion of cellular NAD that accelerates aging. Oxidative damage to calcium transporters leads to calcium overload and more frequent opening of mPTP. Because aging enhances the opening of the mPTP and mPTP opening accelerates aging, we suggest that mPTP opening drives the progression of aging. Activation of the mPTP is regulated, directly and indirectly, not only by the mitochondrial protection pathways that are induced by mROS, but also by pro-apoptotic signals that are induced by DNA damage. We suggest that the integration of these contrasting signals by the mPTP largely determines the rate of cell aging and the initiation of cell death, and thus animal lifespan. The suggestion that the control of mPTP activation is critical for the progression of aging can explain the conflicting and confusing evidence regarding the beneficial and deleterious effects of mROS on health and lifespan. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Believing and perceiving: authorship belief modulates sensory attenuation.

Directory of Open Access Journals (Sweden)

Andrea Desantis

Full Text Available Sensory attenuation refers to the observation that self-generated stimuli are attenuated, both in terms of their phenomenology and their cortical response compared to the same stimuli when generated externally. Accordingly, it has been assumed that sensory attenuation might help individuals to determine whether a sensory event was caused by themselves or not. In the present study, we investigated whether this dependency is reciprocal, namely whether sensory attenuation is modulated by prior beliefs of authorship. Participants had to judge the loudness of auditory effects that they believed were either self-generated or triggered by another person. However, in reality, the sounds were always triggered by the participants' actions. Participants perceived the tones' loudness attenuated when they believed that the sounds were self-generated compared to when they believed that they were generated by another person. Sensory attenuation is considered to contribute to the emergence of people's belief of authorship. Our results suggest that sensory attenuation is also a consequence of prior belief about the causal link between an action and a sensory change in the environment.

Radiation-attenuated vaccine for lungworm disease

International Nuclear Information System (INIS)

Singh, C.M.

1977-01-01

The work done at the Indian Veternary Research Institute, Izatnagar, on the development of a vaccine for lungworm diseases is reported. Research work done includes: (1) studies on the epidemiology and the incidence of the lungworm infections, (ii) studies on the radiation-attenuated lungworm Dictyocaulus filaria vaccine, (iii) studies on other parasites using ionizing radiation, (iv) incidence of lungworm infection in sheep in Jammu and Kashmir State, (v) suitable dose of gamma radiation for attenuation, (vi) laboratory studies with radiation-attenuated D. filaria vaccine, (vii) serology of D. filaria infection, (viii) field trials with the radiation-attenuated vaccine, (ix) immune response of previously exposed lambs to vaccination, (x) comparative susceptibility of sheep and goats to infection with D. filaria, (xi) quantitative studies of D. filaria in lambs and (xii) production and supply of lungworm vaccine. (A.K.)

Analysis of biological samples by x-ray attenuation measurements

International Nuclear Information System (INIS)

Cesareo, R.

1988-01-01

Over the last few years there has been an increasing interest in X-ray attenuation measurements, mainly due to the enormous development of computer assisted tomography (CAT). With CAT, analytical information concerning the density and the mean atomic number distributions in a sample is deduced from a large number of attenuation measurements. Particular transmission methods developed, based on the differential attenuation method are discussed. The theoretical background for attenuation of radiation and for differential attenuation of radiation is given. Details about the generation of monoenergetic X-rays are discussed. Applications of attenuation measurements in the field of Medicine are presented

Unfocused beam patterns in nonattenuating and attenuating fluids

International Nuclear Information System (INIS)

Goldstein, Albert

2004-01-01

The most important aspect of an ultrasound measuring system is knowledge of the transducer beam pattern. At all depths accurate single integral equations have been derived for the full beam pattern of steady state unfocused circular flat piston sources radiating into nonattenuating and attenuating fluids. The axial depth of the beginning of the unattenuated beam pattern far field is found to be at 6.41Y 0 . The unattenuated single integral equations are identical to a Jinc function directivity term at this and deeper depths. For attenuating fluids values of α and z are found that permit the attenuated axial pressure to be represented by a plane wave multiplicative exponential attenuation factor. This knowledge will aid in the experimental design of highly accurate attenuation measurements. Accurate single integral equations for the attenuated full beam pattern are derived using complex Bessel functions

Activation of the Nrf2-ARE pathway by siRNA knockdown of Keap1 reduces oxidative stress and provides partial protection from MPTP-mediated neurotoxicity.

Science.gov (United States)

Williamson, Tracy P; Johnson, Delinda A; Johnson, Jeffrey A

2012-06-01

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that binds to the antioxidant response element, a cis-acting regulatory element that increases expression of detoxifying enzymes and antioxidant proteins. Kelch-like ECH associating protein 1 (Keap1) protein is a negative regulator of Nrf2. Previous work has shown that genetic overexpression of Nrf2 is protective in vitro and in vivo. To modulate the Nrf2-ARE system without overexpressing Nrf2, we used short interfering RNA (siRNA) directed against Keap1. Keap1 siRNA administration in primary astrocytes increased the levels of Nrf2-ARE driven genes and protected against oxidative stress. Moreover, Keap1 siRNA resulted in a persistent upregulation of the Nrf2-ARE pathway and protection against oxidative stress in primary astrocytes. Keap1 siRNA injected into the striatum was also modestly protective against MPTP-induced dopaminergic terminal damage. These data indicate that activation of endogenous intracellular levels of Nrf2 is sufficient to protect in models of oxidative stress and Parkinson's disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Fuselage panel noise attenuation by piezoelectric switching control

International Nuclear Information System (INIS)

Makihara, Kanjuro; Onoda, Junjiro; Minesugi, Kenji; Miyakawa, Takeya

2010-01-01

This paper describes a problem that we encountered in our noise attenuation project and our solution for it. We intend to attenuate low-frequency noise that transmits through aircraft fuselage panels. Our method of noise attenuation is implemented with a piezoelectric semi-active system having a selective switch instead of an active energy-supply system. The semi-active controller is based on the predicted sound pressure distribution obtained from acoustic emission analysis. Experiments and numerical simulations demonstrate that the semi-active method attenuates acoustic levels of not only the simple monochromatic noise but also of broadband noise. We reveal that tuning the electrical parameters in the circuit is the key to effective noise attenuation, to overcome the acoustic excitation problem due to sharp switching actions, as well as to control chattering problems. The results obtained from this investigation provide meaningful insights into designing noise attenuation systems for comfortable aircraft cabin environments

BAX channel activity mediates lysosomal disruption linked to Parkinson disease.

Science.gov (United States)

Bové, Jordi; Martínez-Vicente, Marta; Dehay, Benjamin; Perier, Celine; Recasens, Ariadna; Bombrun, Agnes; Antonsson, Bruno; Vila, Miquel

2014-05-01

Lysosomal disruption is increasingly regarded as a major pathogenic event in Parkinson disease (PD). A reduced number of intraneuronal lysosomes, decreased levels of lysosomal-associated proteins and accumulation of undegraded autophagosomes (AP) are observed in PD-derived samples, including fibroblasts, induced pluripotent stem cell-derived dopaminergic neurons, and post-mortem brain tissue. Mechanistic studies in toxic and genetic rodent PD models attribute PD-related lysosomal breakdown to abnormal lysosomal membrane permeabilization (LMP). However, the molecular mechanisms underlying PD-linked LMP and subsequent lysosomal defects remain virtually unknown, thereby precluding their potential therapeutic targeting. Here we show that the pro-apoptotic protein BAX (BCL2-associated X protein), which permeabilizes mitochondrial membranes in PD models and is activated in PD patients, translocates and internalizes into lysosomal membranes early following treatment with the parkinsonian neurotoxin MPTP, both in vitro and in vivo, within a time-frame correlating with LMP, lysosomal disruption, and autophagosome accumulation and preceding mitochondrial permeabilization and dopaminergic neurodegeneration. Supporting a direct permeabilizing effect of BAX on lysosomal membranes, recombinant BAX is able to induce LMP in purified mouse brain lysosomes and the latter can be prevented by pharmacological blockade of BAX channel activity. Furthermore, pharmacological BAX channel inhibition is able to prevent LMP, restore lysosomal levels, reverse AP accumulation, and attenuate mitochondrial permeabilization and overall nigrostriatal degeneration caused by MPTP, both in vitro and in vivo. Overall, our results reveal that PD-linked lysosomal impairment relies on BAX-induced LMP, and point to small molecules able to block BAX channel activity as potentially beneficial to attenuate both lysosomal defects and neurodegeneration occurring in PD.

Elastic wave attenuation in rocks containing fluids

International Nuclear Information System (INIS)

Berryman, J.G.

1986-01-01

The low-frequency limit of Biot's theory of fluid-saturated porous media predicts that the coefficients for viscous attenuation of shear waves and of the fast compressional wave are proportional to the fluid permeability. Although the observed attenuation is generally in qualitative agreement with the theory, the magnitude of the observed attenuation coefficient in rocks is often more than an order of magnitude higher than expected. This apparent dilemma can be resolved without invoking other attenuation mechanisms if the intrinsic permeability of the rock is inhomogeneous and varies widely in magnitude. A simple calculation of the overall behavior of a layered porous material using local-flow Biot theory shows that the effective permeability for attenuation is the mean of the constituent permeabilities while the effective permeability for fluid flow is the harmonic mean. When the range of variation in the local permeability is one or more orders of magnitude, this difference in averaging method can easily explain some of the observed discrepancies

Estimating Rain Attenuation In Satellite Communication Links

Science.gov (United States)

Manning, R. M.

1991-01-01

Attenuation computed with help of statistical model and meteorological data. NASA Lewis Research Center Satellite Link Attenuation Model (SLAM) program QuickBASIC computer program evaluating static and dynamic statistical assessment of impact of rain attenuation on communication link established between Earth terminal and geosynchronous satellite. Application in specification, design, and assessment of satellite communication links for any terminal location in continental United States. Written in Microsoft QuickBASIC.

An acoustic eikonal equation for attenuating orthorhombic media

KAUST Repository

Hao, Qi

2017-04-06

Attenuating orthorhombic models are often used to describe the azimuthal variation of the seismic wave velocity and amplitude in finely layered hydrocarbon reservoirs with vertical fractures. In addition to the P-wave related medium parameters, shear wave parameters are also present in the complex eikonal equation needed to describe the P-wave complex-valued traveltime in an attenuating orthorhombic medium, which increases the complexity of using the P-wave traveltime to invert for the medium parameters in practice. Here, we use the acoustic assumption to derive an acoustic eikonal equation that approximately governs the complex-valued traveltime of P-waves in an attenuating orthorhombic medium. For a homogeneous attenuating orthorhombic media, we solve the eikonal equation using a combination of the perturbation method and Shanks transform. For a horizontal attenuating orthorhombic layer, both the real and imaginary part of the complex-valued reflection traveltime have nonhyperbolic behaviors in terms of the source-receiver offset. Similar to the roles of normal moveout (NMO) velocity and anellipticity, the attenuation NMO velocity and the attenuation anellipticity characterize the variation of the imaginary part of the complex-valued reflection traveltime around zero source-receiver offset.

Correlation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity with blood-brain barrier monoamine oxidase activity

International Nuclear Information System (INIS)

Kalaria, R.N.; Mitchell, M.J.; Harik, S.I.

1987-01-01

Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes parkinsonism in humans and subhuman primates, but not in rats and many other laboratory animals; mice are intermediate in their susceptibility. Since MPTP causes selective dopaminergic neurotoxicity when infused directly into rat substantia nigra, the authors hypothesized that systemic MPTP may be metabolized by monoamine oxidase and/or other enzymes in rat brain capillaries and possibly other peripheral organs and thus prevented from reaching its neuronal sites of toxicity. They tested this hypothesis by assessing monoamine oxidase in isolated cerebral microvessels of humans, rats, and mice by measuring the specific binding of [ 3 H]pargyline, an irreversible monoamine oxidase inhibitor, and by estimating the rates of MPTP and benzylamine oxidation. [ 3 H]Pargyline binding to rat cerebral microvessels was about 10-fold higher than to human or mouse microvessels. Also, MPTP oxidation by rat brain microvessels was about 30-fold greater than by human microvessels; mouse microvessels yielded intermediate values. These results may explain, at least in part, the marked species differences in susceptibility to systemic MPTP. They also suggest the potential importance of enzyme barriers at the blood-brain interface that can metabolize toxins not excluded by structural barriers, and may provide biological bases for developing therapeutic strategies for the prevention of MPTP-induced neurotoxicity and other neurotoxic conditions including, possibly, Parkinson's disease

Proteomic Analysis of the Effect of Korean Red Ginseng in the Striatum of a Parkinson's Disease Mouse Model.

Science.gov (United States)

Kim, Dongsoo; Jeon, Hyongjun; Ryu, Sun; Koo, Sungtae; Ha, Ki-Tae; Kim, Seungtae

2016-01-01

Recent studies have shown that Korean Red Ginseng (KRG) suppresses dopaminergic neuronal death in the brain of a Parkinson's disease (PD) mouse model, but the mechanism is still elusive. Using a 2-dimensional electrophoresis technique, we investigated whether KRG can restore the changes in protein expressions in the striatum (ST) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-injected mice. Male C57BL/6 mice (9 weeks old) were injected with 20 mg/kg MPTP intraperitoneally four times at 2-h intervals. KRG (100 mg/kg) was orally administered once a day for 3 days from one hour after the first MPTP injection. Two hours after the third KRG administration a pole test was performed to evaluate motor function, after which the brains were immediately harvested. Survival of dopaminergic neurons in the nigrostriatal pathway and protein expression in the ST were measured by immunohistochemistry and 2-dimensional electrophoresis. KRG suppressed MPTP-induced behavioral dysfunction and neuronal death in the nigrostriatal pathway. Moreover, 30 proteins changed by MPTP and KRG in the ST were identified and shown to be related to glycolysis/gluconeogenesis and neurodegenerative diseases including Alzheimer's disease and PD. KRG has neuroprotective effects against MPTP toxicity and alleviates protein expression profiles related to enhancing energy metabolism in the ST of MPTP-treated mice.

Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design

Energy Technology Data Exchange (ETDEWEB)

Yamshchikov, Vladimir, E-mail: yaximik@gmail.com; Manuvakhova, Marina; Rodriguez, Efrain

2016-01-15

Direct attenuation of West Nile (WN) virus strain NY99 for the purpose of vaccine development is not feasible due to its high virulence and pathogenicity. Instead, we created highly attenuated chimeric virus W1806 with the serological identity of NY99. To further attenuate W1806, we investigated effects of mutations found in Japanese encephalitis virus vaccine SA14-14-2. WN viruses carrying all attenuating mutations lost infectivity in mammalian, but not in mosquito cells. No single reversion restored infectivity in mammalian cells, although increased infectivity in mosquito cells was observed. To identify a subset of mutations suitable for further attenuation of W1806, we analyzed effects of E{sub 138}K and K{sub 279}M changes on virulence, growth properties, and immunogenicity of derivatized W956, from which chimeric W1806 inherited its biological properties and attenuation profile. Despite strong dominant attenuating effect, introduction of only two mutations was not sufficient for attenuating W1806 to the safety level acceptable for human use. - Highlights: • Further attenuation of a WN vaccine precursor is outlined. • Effect of SA14-14-2 attenuating mutations is tested. • Mechanism of attenuation is proposed and illustrated. • The need for additional attenuating mutations is justified.

An attenuated projector-backprojector for iterative SPECT reconstruction

International Nuclear Information System (INIS)

Gullberg, G.T.; Pelc, N.J.; Huesman, R.H.; Budinger, T.F.; Malko, J.A.

1985-01-01

A new ray-driven projector-backprojector which can easily be adapted for hardware implementation is described and simulated in software. The projector-backprojector discretely models the attenuated Radon transform of a source distributed within an attenuating medium as line integrals of discrete pixels, obtained using the standard sampling technique of averaging the emission source or attenuation distribution over small square regions. Attenuation factors are calculated for each pixel during the projection and backprojection operations instead of using precalculated values. The calculation of the factors requires a specification of the attenuation distribution, estimated either from an assumed constant distribution and an approximate body outline or from transmission measurements. The distribution of attenuation coefficients is stored in memory for efficient access during the projection and backprojection operations. The reconstruction of the source distribution is obtained by using a conjugate gradient or SIRT type iterative algorithm which requires one projection and one backprojection operation for each iteration. (author)

Photostimulated attenuation of hypersound in superlattice

International Nuclear Information System (INIS)

Mensah, S.Y.; Allotey, F.K.; Adjepong, S.K.

1992-10-01

Photostimulated attenuation of hypersound in semiconductor superlattice has been investigated. It is shown that the attenuation coefficient depends on the phonon wave vector q in an oscillatory manner and that from this oscillation the band width Δ of superlattice can be found. (author). 14 refs, 1 fig

Calculation Of Pneumatic Attenuation In Pressure Sensors

Science.gov (United States)

Whitmore, Stephen A.

1991-01-01

Errors caused by attenuation of air-pressure waves in narrow tubes calculated by method based on fundamental equations of flow. Changes in ambient pressure transmitted along narrow tube to sensor. Attenuation of high-frequency components of pressure wave calculated from wave equation derived from Navier-Stokes equations of viscous flow in tube. Developed to understand and compensate for frictional attenuation in narrow tubes used to connect aircraft pressure sensors with pressure taps on affected surfaces.

Dose reduction using a dynamic, piecewise-linear attenuator

Energy Technology Data Exchange (ETDEWEB)

Hsieh, Scott S., E-mail: sshsieh@stanford.edu [Department of Radiology, Stanford University, Stanford, California 94305 and Department of Electrical Engineering, Stanford University, Stanford, California 94305 (United States); Fleischmann, Dominik [Department of Radiology, Stanford University, Stanford, California 94305 (United States); Pelc, Norbert J. [Department of Radiology, Stanford University, Stanford, California 94305 and Department of Bioengineering, Stanford University, Stanford, California 94305 (United States)

2014-02-15

Purpose: The authors recently proposed a dynamic, prepatient x-ray attenuator capable of producing a piecewise-linear attenuation profile customized to each patient and viewing angle. This attenuator was intended to reduce scatter-to-primary ratio (SPR), dynamic range, and dose by redistributing flux. In this work the authors tested the ability of the attenuator to reduce dose and SPR in simulations. Methods: The authors selected four clinical applications, including routine full field-of-view scans of the thorax and abdomen, and targeted reconstruction tasks for an abdominal aortic aneurysm and the pancreas. Raw data were estimated by forward projection of the image volume datasets. The dynamic attenuator was controlled to reduce dose while maintaining peak variance by solving a convex optimization problem, assuminga priori knowledge of the patient anatomy. In targeted reconstruction tasks, the noise in specific regions was given increased weighting. A system with a standard attenuator (or “bowtie filter”) was used as a reference, and used either convex optimized tube current modulation (TCM) or a standard TCM heuristic. The noise of the scan was determined analytically while the dose was estimated using Monte Carlo simulations. Scatter was also estimated using Monte Carlo simulations. The sensitivity of the dynamic attenuator to patient centering was also examined by shifting the abdomen in 2 cm intervals. Results: Compared to a reference system with optimized TCM, use of the dynamic attenuator reduced dose by about 30% in routine scans and 50% in targeted scans. Compared to the TCM heuristics which are typically used withouta priori knowledge, the dose reduction is about 50% for routine scans. The dynamic attenuator gives the ability to redistribute noise and variance and produces more uniform noise profiles than systems with a conventional bowtie filter. The SPR was also modestly reduced by 10% in the thorax and 24% in the abdomen. Imaging with the dynamic

Seismic attenuation system for a nuclear reactor

Energy Technology Data Exchange (ETDEWEB)

Liszkai, Tamas; Cadell, Seth

2018-01-30

A system for attenuating seismic forces includes a reactor pressure vessel containing nuclear fuel and a containment vessel that houses the reactor pressure vessel. Both the reactor pressure vessel and the containment vessel include a bottom head. Additionally, the system includes a base support to contact a support surface on which the containment vessel is positioned in a substantially vertical orientation. An attenuation device is located between the bottom head of the reactor pressure vessel and the bottom head of the containment vessel. Seismic forces that travel from the base support to the reactor pressure vessel via the containment vessel are attenuated by the attenuation device in a direction that is substantially lateral to the vertical orientation of the containment vessel.

Mitochondrial permeability transition and cell death: the role of cyclophilin D

Directory of Open Access Journals (Sweden)

Sabzali eJavadov

2013-04-01

Full Text Available Mitochondria serve as a powerhouse which provides near 90% of ATP necessary for cell life. However, recent studies provide strong evidence that mitochondria also play a central role in cell death. Irreversible mitochondrial permeability transition (mPT at high conductance in response to oxidative or other cellular stresses is accompanied by formation of pathological and non-specific mPT pores (mPTP in the inner membrane of mitochondria. Mitochondrial PTP can serve as a target to prevent cell death under pathological conditions such as cardiac and brain ischemia/reperfusion injury and diabetes. On the other hand, mPTP can be used as an executioner to specifically induce cell death thus blocking tumorigenesis in cancer diseases. Despite many studies, the molecular identity of the mPTP remains unclear. At present, cyclophilin D (CyP-D represents the only mPTP protein which plays an essential role in pore formation. This review will discuss direct and indirect mechanisms underlying CyP-D interaction with a target protein of the mPTP complex. Understanding of the mechanisms of mPTP formation will be helpful to further develop new pharmacological agents targeting mitochondria-mediated cell death.

In vivo tomographic study of cerebral blood perfusion with SPECT in hemiparkinsonian monkeys

International Nuclear Information System (INIS)

Chen Shengdi; Xu Delong

1994-01-01

The authors present data on the utility of functional brain imaging with 99m Tc-ECD and SPECT in the study of MPTP induced hemiparkinsonism in monkeys. Injection of MPTP into the right common carotid artery of 10 rhesus monkeys produced hemiparkinsonism in the contralateral limbs which responded to antiparkinsonian medication. The unilateral neurotoxicity of the MPTP treated side was confirmed biochemically by marked reduction of DA contents in the nigrostriatum and histologically by selective neuronal loss in the substantia nigra. These monkeys with hemiparkinsonism were studied with SPECT using 99m Tc-ECD as perfusion marker. The results of brain scanning showed that the cerebral blood perfusion of MPTP treated side was significantly depleted 20∼90 days after MPTP intoxication, and returned to normal 8 months after perfusion. The experiment indicates that abnormal cerebral blood perfusion is involved in the course of parkinsonian pathophysiology

Electron Effective-Attenuation-Length Database

Science.gov (United States)

SRD 82 NIST Electron Effective-Attenuation-Length Database (PC database, no charge)   This database provides values of electron effective attenuation lengths (EALs) in solid elements and compounds at selected electron energies between 50 eV and 2,000 eV. The database was designed mainly to provide EALs (to account for effects of elastic-eletron scattering) for applications in surface analysis by Auger-electron spectroscopy (AES) and X-ray photoelectron spectroscopy (XPS).

Attenuation in Melting Layer of Precipitation

NARCIS (Netherlands)

Klaassen, W.

1988-01-01

A model of the melting layer is employed on radar measurements to simulate the attenuation of radio waves at 12, 20 and 30GHz. The attenuation in the melting layer is simulated to be slightly larger than that of rain with the same path length and precipitation intensity. The result appears to depend

Involvement of microRNA-135a-5p in the Protective Effects of Hydrogen Sulfide Against Parkinson's Disease

Directory of Open Access Journals (Sweden)

Yuanyuan Liu

2016-11-01

Full Text Available Background/Aims: Development of effective therapeutic drugs for Parkinson's disease is in great need. During the progression of Parkinson's disease, Rho-associated protein kinase 2 (ROCK2 is activated to promote neurodegeneration. Hydrogen sulfide (H2S has a neuroprotective effect during the neural injury of Parkinson's disease. However, the mechanisms that underlie the effects of ROCK2 and H2S remain ill-defined. In the current study, we addressed these questions. Methods: We used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-induced mouse subacute model of Parkinson's disease to study the effects of H2S on astrocytic activation in the mouse striatum, on the levels of tyrosine-hydroxylase (TH-positive neuron loss, on the apomorphine-induced rotational behavior of the mice, and on the changes in ROCK2 and miR-135a-5p expression. Plasmid transfection was applied to modify miR-135a-5p levels in a neuronal cell line HCN-1A. Bioinformatics analysis was performed to predict the relationship between ROCK2 and miR-135a-5p in neuronal cells, and then was confirmed by luciferase reporter assay. Results: H2S alleviated MPTP-induced astrocytic activation in the mouse striatum, alleviated the increases in TH-positive neuron loss, and improved the apomorphine-induced rotational behavior of the mice. H2S significantly attenuated the increases in ROCK2 and the decreases in miR-135a-5p by MPTP. MiR-135a-5p targeted the 3'-UTR of ROCK2 mRNA to inhibit its translation in neuronal cells. Conclusion: MiR-135a-5p-regulated ROCK2 may play a role in the protective effects of hydrogen sulfide against Parkinson's disease.

GNX-4728, a Novel Small Molecule Drug Inhibitor of Mitochondrial Permeability Transition, is Therapeutic in a Mouse Model of Amyotrophic Lateral Sclerosis

Directory of Open Access Journals (Sweden)

Lee J Martin

2014-12-01

Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurological disorder in humans characterized by progressive degeneration of skeletal muscle and motor neurons in spinal cord, brainstem, and cerebral cortex causing skeletal muscle paralysis, respiratory insufficiency, and death. There are no cures or effective treatments for ALS. ALS can be inherited, but most cases are not associated with a family history of the disease. Mitochondria have been implicated in the pathogenesis but definitive proof of causal mechanisms is lacking. Identification of new clinically translatable disease mechanism-based molecular targets and small molecule drug candidates are needed for ALS patients. We tested the hypothesis in an animal model that drug modulation of the mitochondrial permeability transition pore (mPTP is therapeutic in ALS. A prospective randomized placebo-controlled drug trial was done in a transgenic mouse model of ALS. We explored GNX-4728 as a therapeutic drug. GNX-4728 inhibits mPTP opening as evidenced by increased mitochondrial calcium retention capacity both in vitro and in vivo. Chronic systemic treatment of G37R-human mutant superoxide dismutase-1 (hSOD1 transgenic mice with GNX-4728 resulted in major therapeutic benefits. GNX-4728 slowed disease progression and significantly improved motor function. The survival of ALS mice was increased significantly by GNX-4728 treatment as evidence by a nearly 2-fold extension of lifespan (360 days to 750 days. GNX-4728 protected against motor neuron degeneration and mitochondrial degeneration, attenuated spinal cord inflammation, and preserved neuromuscular junction innervation in the diaphragm in ALS mice. This work demonstrates that a mPTP-acting drug has major disease-modifying efficacy in a preclinical mouse model of ALS and establishes mitochondrial calcium retention, and indirectly the mPTP, as targets for ALS drug development.

Attenuation of earmuffs used simultaneously with respiratory protective devices

Directory of Open Access Journals (Sweden)

Emil Kozłowski

2017-06-01

Full Text Available Background: In the work environment, apart from the noise, employees may be exposed to other harmful factors. Therefore, they wear hearing protectors and other personal protective equipment. The aim of the study was to determine whether simultaneous use of earmuffs and respiratory protective devices affects the attenuation of earmuffs. Material and Methods: The study was conducted in laboratory conditions using the subjective REAT (Real Ear Attenuation at Threshold and objective MIRE (Microphone in Real Ear methods. The REAT method was used to measure sound attenuation of earmuffs, while MIRE was used to determine changes in attenuation of earmuffs due to the use of other personal protective equipment. Results: The study showed reduction in attenuation of earmuffs due to the use of a full face mask up to 20 dB. Using a full face mask causes that attenuation of earmuffs in the low frequency range is close to zero. Reduction in attenuation due to the use of half masks for complete with particle filters (half masks is 3–15 dB. Simultaneous use of earmuffs and filtering half masks makes small changes in attenuation not exceeding 3 dB. Conclusions: The study showed that full face masks give the greatest reduction in attenuation of earmuffs. On the other hand, the least reduction is observed in the case of filtering half masks. There is a significant difference between the reduction in attenuation of earmuffs worn with half masks for complete with particle filters because they may be equipped with different kind of the head strap. Med Pr 2017;68(3:349–361

GPR measurements of attenuation in concrete

Science.gov (United States)

Eisenmann, David; Margetan, Frank J.; Pavel, Brittney

2015-03-01

Ground-penetrating radar (GPR) signals from concrete structures are affected by several phenomenon, including: (1) transmission and reflection coefficients at interfaces; (2) the radiation patterns of the antenna(s) being used; and (3) the material properties of concrete and any embedded objects. In this paper we investigate different schemes for determining the electromagnetic (EM) attenuation of concrete from measured signals obtained using commercially-available GPR equipment. We adapt procedures commonly used in ultrasonic inspections where one compares the relative strengths of two or more signals having different travel paths through the material of interest. After correcting for beam spread (i.e., diffraction), interface phenomena, and equipment amplification settings, any remaining signal differences are assumed to be due to attenuation thus allowing the attenuation coefficient (say, in dB of loss per inch of travel) to be estimated. We begin with a brief overview of our approach, and then discuss how diffraction corrections were determined for our two 1.6 GHz GPR antennas. We then present results of attenuation measurements for two types of concrete using both pulse/echo and pitch/catch measurement setups.

GPR measurements of attenuation in concrete

International Nuclear Information System (INIS)

Eisenmann, David; Margetan, Frank J.; Pavel, Brittney

2015-01-01

Ground-penetrating radar (GPR) signals from concrete structures are affected by several phenomenon, including: (1) transmission and reflection coefficients at interfaces; (2) the radiation patterns of the antenna(s) being used; and (3) the material properties of concrete and any embedded objects. In this paper we investigate different schemes for determining the electromagnetic (EM) attenuation of concrete from measured signals obtained using commercially-available GPR equipment. We adapt procedures commonly used in ultrasonic inspections where one compares the relative strengths of two or more signals having different travel paths through the material of interest. After correcting for beam spread (i.e., diffraction), interface phenomena, and equipment amplification settings, any remaining signal differences are assumed to be due to attenuation thus allowing the attenuation coefficient (say, in dB of loss per inch of travel) to be estimated. We begin with a brief overview of our approach, and then discuss how diffraction corrections were determined for our two 1.6 GHz GPR antennas. We then present results of attenuation measurements for two types of concrete using both pulse/echo and pitch/catch measurement setups

GPR measurements of attenuation in concrete

Energy Technology Data Exchange (ETDEWEB)

Eisenmann, David, E-mail: djeisen@cnde.iastate.edu; Margetan, Frank J., E-mail: djeisen@cnde.iastate.edu; Pavel, Brittney, E-mail: djeisen@cnde.iastate.edu [Center for Nondestructive Evaluation, Iowa State University, 1915 Scholl Road, Ames, IA 50011-3042 (United States)

2015-03-31

Ground-penetrating radar (GPR) signals from concrete structures are affected by several phenomenon, including: (1) transmission and reflection coefficients at interfaces; (2) the radiation patterns of the antenna(s) being used; and (3) the material properties of concrete and any embedded objects. In this paper we investigate different schemes for determining the electromagnetic (EM) attenuation of concrete from measured signals obtained using commercially-available GPR equipment. We adapt procedures commonly used in ultrasonic inspections where one compares the relative strengths of two or more signals having different travel paths through the material of interest. After correcting for beam spread (i.e., diffraction), interface phenomena, and equipment amplification settings, any remaining signal differences are assumed to be due to attenuation thus allowing the attenuation coefficient (say, in dB of loss per inch of travel) to be estimated. We begin with a brief overview of our approach, and then discuss how diffraction corrections were determined for our two 1.6 GHz GPR antennas. We then present results of attenuation measurements for two types of concrete using both pulse/echo and pitch/catch measurement setups.

A miniaturized reconfigurable broadband attenuator based on RF MEMS switches

International Nuclear Information System (INIS)

Guo, Xin; Gong, Zhuhao; Zhong, Qi; Liang, Xiaotong; Liu, Zewen

2016-01-01

Reconfigurable attenuators are widely used in microwave measurement instruments. Development of miniaturized attenuation devices with high precision and broadband performance is required for state-of-the-art applications. In this paper, a compact 3-bit microwave attenuator based on radio frequency micro-electro-mechanical system (RF MEMS) switches and polysilicon attenuation modules is presented. The device comprises 12 ohmic contact MEMS switches, π -type polysilicon resistive attenuation modules and microwave compensate structures. Special attention was paid to the design of the resistive network, compensate structures and system simulation. The device was fabricated using micromachining processes compatible with traditional integrated circuit fabrication processes. The reconfigurable attenuator integrated with RF MEMS switches and resistive attenuation modules was successfully fabricated with dimensions of 2.45  ×  4.34  ×  0.5 mm 3 , which is 1/1000th of the size of a conventional step attenuator. The measured RF performance revealed that the attenuator provides 10–70 dB attenuation at 10 dB intervals from 0.1–20 GHz with an accuracy better than  ±1.88 dB at 60 dB and an error of less than 2.22 dB at 10 dB. The return loss of each state of the 3-bit attenuator was better than 11.95 dB (VSWR  <  1.71) over the entire operating band. (paper)

Chlorinated Iridoid Glucosides from Veronica longifolia and their Antioxidant Activity

DEFF Research Database (Denmark)

Jensen, Søren Rosendal; Gotfredsen, Charlotte Held; Harput, U. Sebnem

2010-01-01

From Veronica longifolia were isolated three chlorinated iridoid glucosides, namely asystasioside E (6) and its 6-O-esters 6a and 6b, named longifoliosides A and B, respectively. The structures of 6a and 6b were proved by analysis of their spectroscopic data and by conversion to the catalpol ester...

Fat Attenuation at CT in Anorexia Nervosa

Science.gov (United States)

Gill, Corey M.; Torriani, Martin; Murphy, Rachel; Harris, Tamara B.; Miller, Karen K.; Klibanski, Anne

2016-01-01

Purpose To investigate the composition, cross-sectional area (CSA), and hormonal correlates of different fat depots in women with anorexia nervosa (AN) and control subjects with normal weights to find out whether patients with AN have lower fat CSA but higher attenuation than did control subjects and whether these changes may be mediated by gonadal steroids, cortisol, and thyroid hormones. Materials and Methods This study was institutional review board approved and HIPAA compliant. Written informed consent was obtained. Forty premenopausal women with AN and 40 normal-weight women of comparable age (mean age ± standard deviation, 26 years ± 5) were studied. All individuals underwent computed tomography of the abdomen and thigh with a calibration phantom. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), thigh SAT, and thigh intermuscular adipose tissue CSA and attenuation were quantified. Serum estradiol, thyroid hormones, and urinary free cortisol levels were assessed. Variables were compared by using analysis of variance. Associations were examined by using linear regression analysis. Results Women with AN had higher fat attenuation than did control subjects (−100.1 to −46.7 HU vs −117.6 to −61.8 HU, P < .0001), despite lower fat CSA (2.0–62.8 cm2 vs 5.5–185.9 cm2, P < .0001). VAT attenuation but not CSA was inversely associated with lowest prior lifetime body mass index in AN (r = −0.71, P = .006). Serum estradiol levels were inversely associated with fat attenuation (r = −0.34 to −0.61, P = .03 to <.0001) and were positively associated with fat CSA of all compartments (r = 0.42–0.64, P = .007 to <.0001). Thyroxine levels and urinary free cortisol levels were positively associated with thigh SAT attenuation (r = 0.64 [P = .006] and r = 0.68 [P = .0004], respectively) and were inversely associated with abdominal SAT and VAT CSA (r = −0.44 to −0.58, P = .04 to .02). Conclusion Women with AN have differences in fat

Lg Attenuation Modeling in the Middle East

Science.gov (United States)

Pasyanos, M. E.; Matzel, E. M.; Walter, W. R.; Rodgers, A. J.

2008-12-01

We present a broadband tomographic model of Lg attenuation in the Middle East derived from source- and site-corrected amplitudes. The study region spans from Turkey through the Arabian Peninsula and Iran to Pakistan, Afghanistan, and northwest India. Absolute amplitude measurements are made on hand-selected and carefully windowed seismograms for tens of stations and thousands of crustal earthquakes resulting in excellent coverage of the region. We have modified the standard attenuation tomography technique to more explicitly define the earthquake source expression in terms of the seismic moment. This facilitates the use of the model to predict the expected amplitudes of new events, an important consideration for earthquake hazard or explosion monitoring applications. We will discuss the updated method and implications of this parameterization. A conjugate gradient method is used to tomographically invert the amplitude dataset of over 8000 paths. We solve for Q variation, as well as site and source terms, for a wide range of frequencies ranging from 0.5 -- 10 Hz. The attenuation results have a strong correlation to tectonics. Shields have low attenuation, while tectonic regions have high attenuation, with the highest attenuation at 1 Hz found in eastern Turkey. The results also compare favorably to other studies in the region made using Lg propagation efficiency, Lg/Pg amplitude ratios and two-station methods. We tomographically invert the amplitude measurements for each frequency independently. In doing so, it appears the frequency-dependence of attenuation is not compatible with the power law representation of Q(f). This research was performed under the auspices of the U.S. Department of Energy by the Lawrence Livermore National Laboratory under contract number DE-AC52-07NA27344. This is LLNL contribution LLNL-ABS-406761.

Treatment with Docosahexaenoic Acid, but Not Eicosapentaenoic Acid, Delays Ca2+-Induced Mitochondria Permeability Transition in Normal and Hypertrophied Myocardium

OpenAIRE

Khairallah, Ramzi J.; O'Shea, Karen M.; Brown, Bethany H.; Khanna, Nishanth; Des Rosiers, Christine; Stanley, William C.

2010-01-01

Intake of fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) prevents heart failure; however, the mechanisms are unclear. Mitochondrial permeability transition pore (MPTP) opening contributes to myocardial pathology in cardiac hypertrophy and heart failure, and treatment with DHA + EPA delays MPTP opening. Here, we assessed: 1) whether supplementation with both DHA and EPA is needed for optimal prevention of MPTP opening, and 2) whether this benefit occurs in hyper...

125I-β-CIT imaging study of striatal dopamine transporters in mice model of parkinsonism

International Nuclear Information System (INIS)

Liu Zhenguo; Sun Wenshan; Weng Zhongfang; Chen Shengdi; Shen Minghua; Zhu Chengmo

2001-01-01

Objective: To detect the activity of striatal dopamine transporters (DAT) in lesions of different order of severity of MPTP-induced mice model of parkinsonism by autoradiography with 125 I-β-CIT and to evaluate the clinical use of the β-CIT imaging for DAT detection. Methods: With regard to the different duration (days) of MPTP treatment, the C57BL mice were randomly divided into 5 groups, that is MPTP 1, 3, 5 and 7 day groups and control group treated with normal saline instead of MPTP. Two hours after intravenous administration with 125 I-β-CIT of 148 kBq, the brain tissue sections were imaged by autoradiography. The levels of dopamine (DA) and its metabolites were measured by high performance liquid chromatography and electrochemical detection (HPLC-ECD). The tyrosine hydroxylase (TH)-positive cells and fibres in the substantia nigra and striatum of the mice were observed by means of immunohistochemical technique. Results: As compared with control group, the radioactivity ratios of striatum to cortex (ST/CX) in 4 MPTP-treated groups were significantly reduced, by 20%, 42%, 45% and 52%, respectively. The concentrations of DA in the striatum of 4 MPTP-treated groups were remarkably decreased, by 47%, 75%, 95% and 95%, respectively. The gradual loss of DA neurons and fibres in the substantia nigra and striatum in 4 MPTP-treated groups was observed under microscopy. Conclusions: The functional abnormality of DAT paralleled the changes observed in neurochemistry and neuropathology studies in the lesions of different order of injury of the MPTP-treated mice. The β-CIT scanning for the activity of DAT may be useful for diagnosing PD at earlier phase and for monitoring the progression of the disease

Attenuation Measurements in Solutions of Some Carbohydrates

International Nuclear Information System (INIS)

Gagandeep; Singh, Kulwant; Lark, B.S.; Sahota, H.S.

2000-01-01

The linear attenuation coefficients in aqueous solutions of three carbohydrates, glucose (C 6 H 12 O 6 ), maltose monohydrate (C 12 H 22 O 11 .H 2 O), and sucrose (C 12 H 22 O 11 ), were determined at 81, 356, 511, 662, 1173, and 1332 keV by the gamma-ray transmission method in a good geometry setup. From the precisely measured densities of these solutions, mass attenuation coefficients were then obtained that varied systematically with the corresponding changes in the concentrations (g/cm 3 ) of these solutions. The experimental results were used in terms of effective atomic numbers and electron densities. A comparison between experimental and theoretical values of attenuation coefficients has proven that the study has a potential application for the determination of attenuation coefficients of solid solutes from their solutions without obtaining them in pure crystalline form

Bulk viscosity and ultrasonic attenuation in liquid metals

International Nuclear Information System (INIS)

Awasthi, O.N.; Murthy, B.V.S.

1984-11-01

Ultrasonic attenuation in simple liquid metals has been investigated using the thermodynamic theory of relaxation processes incorporating the concept of a two state model for the liquid near the melting point. Agreement of the results with the experimental values of the ultrasonic attenuation and bulk viscosity indicates that this might be an appropriate approach to explain the excess attenuation of ultrasonic waves in liquid metals. (author)

An attenuation measurement technique for rotating planar detector positron tomographs

International Nuclear Information System (INIS)

McNeil, P.A.; Julyan, P.J.; Parker, D.J.

1997-01-01

This paper presents a new attenuation measurement technique suitable for rotating planar detector positron tomographs. Transmission measurements are made using two unshielded positron-emitting line sources, one attached to the front face of each detector. Many of the scattered and accidental coincidences are rejected by including only those coincidences that form a vector passing within a predetermined distance of either line source. Some scattered and accidental coincidences are still included, which reduces the measured linear attenuation; in principle their contribution can be accurately estimated and subtracted, but in practice, when limited statistics are available (as is the case with the multi-wire Birmingham positron camera), this background subtraction unacceptably increases the noise. Instead an attenuation image having the correct features can be reconstructed from the measured projections. For objects containing only a few discrete linear attenuation coefficients, segmentation of this attenuation image reduces noise and allows the correct linear attenuation coefficients to be restored by renormalization. Reprojection through the segmented image may then provide quantitatively correct attenuation correction factors of sufficient statistical quality to correct for attenuation in PET emission images. (author)

Characteristics of Earthquake Ground Motion Attenuation in Korea and Japan

International Nuclear Information System (INIS)

Choi, In-Kil; Choun, Young-Sun; Nakajima, Masato; Ohtori, Yasuki; Yun, Kwan-Hee

2006-01-01

The characteristics of a ground motion attenuation in Korea and Japan were estimated by using the earthquake ground motions recorded at the equal distance observation station by KMA, K-NET and KiK-net of Korea and Japan. The ground motion attenuation equations proposed for Korea and Japan were evaluated by comparing the predicted value for the Fukuoka earthquake with the observed records. The predicted values from the attenuation equations show a good agreement with the observed records and each other. It can be concluded from this study that the ground motion attenuation equations can be used for the prediction of strong ground motion attenuation and for an evaluation of the attenuation equations proposed for Korea

Protective effect of arctigenin against MPP+ and MPTP-induced neurotoxicity.

Science.gov (United States)

Li, Dongwei; Liu, Qingping; Jia, Dong; Dou, Deqiang; Wang, Xiaofei; Kang, Tingguo

2014-01-01

The potential protective effects of arctigenin on 1-methyl-4-phenylpyridinium ion and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyride-induced neurotoxicity were examined, and the results indicated that arctigenin could improve the movement behaviors and upregulate dopamine and γ-aminobutyric acid levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyride-induced neurotoxicity mouse model. A further in vitro experiment showed that the pretreatment with arctigenin on cultured human neuroblastoma SH-SY5Y cells could obviously attenuate the decrease of cell survival rates caused by treatment with 1-methyl-4-phenylpyridinium ion by way of acting against cell apoptosis through the decrease of Bax/Bcl-2 and caspase-3, and by antioxidative action through reduction of the surplus reactive oxygen species production and downregulation of mitochondrial membrane potential. It is for the first time that a neuroprotective activity of arctigenin in both in vitro and in vivo experiments was reported, enlightening that arctigenin could be useful as a potential therapeutic agent for Parkinson's disease. Georg Thieme Verlag KG Stuttgart · New York.

Measurements of earplug attenuation under supra-aural and circumaural headphones.

Science.gov (United States)

Tufts, Jennifer B; Palmer, Jillian V; Marshall, Lynne

2012-10-01

Supra-aural audiometric headphones are generally not recommended for use in measuring the attenuation of earplugs, because contact between the headphone and pinna and/or earplug could alter the attenuation obtained, and because of concerns of non-comparability between modes of excitation from supra-aural headphones and the sound-field procedure required by the standardized method. In this study, we compared measurements of earplug attenuation obtained under Telephonics TDH-50P supra-aural headphones with measurements obtained under circumaural headphones designed expressly for such testing. The attenuation of three types of earplugs (foam, premolded quadruple-flange, and custom-molded) was measured in a repeated-measures design. The study sample comprised 42 normal-hearing adults (21 females, 21 males). With the foam earplugs, nearly all of the attenuation measurements under the supra-aural headphones fell within 10 dB of the measurements under the circumaural headphones. With the flange and custom earplugs, approximately 10% of individuals obtained spuriously high attenuation under the supra-aural headphones. We conclude that standard supra-aural audiometric headphones are suitable for measuring the attenuation provided by foam earplugs. However, supra-aural headphones should not be used to measure the attenuation of flange or custom-molded earplugs. The potential exists for substantial over-estimation of attenuation, especially of custom plugs.

Attenuation measurements in solutions of some carbohydrates

International Nuclear Information System (INIS)

Gagandeep; Singh, K.; Lark, B.S.; Sahota, H.S.

2000-01-01

The linear attenuation coefficients in aqueous solutions of three carbohydrates, glucose (C 6 H 12 O 6 ), maltose monohydrate (C 12 H 22 O 11 ·H 2 O), and sucrose (C 12 H 22 O 11 ), were determined at 81, 356, 511, 662, 1,173, and 1,332 keV by the gamma-ray transmission method in a good geometry setup. From the precisely measured densities of these solutions, mass attenuation coefficients were then obtained that varied systematically with the corresponding changes in the concentrations (g/cm 3 ) of these solutions. The experimental results were used in terms of effective atomic numbers and electron densities. A comparison between experimental and theoretical values of attenuation coefficients has proven that the study has a potential application for the determination of attenuation coefficients of solid solutes from their solutions without obtaining them in pure crystalline form

Mirtazapine attenuates cocaine seeking in rats.

Science.gov (United States)

Barbosa-Méndez, Susana; Leff, Phillipe; Arías-Caballero, Adriana; Hernández-Miramontes, Ricardo; Heinze, Gerardo; Salazar-Juárez, Alberto

2017-09-01

Relapse to cocaine use is a major problem in the clinical treatment of cocaine addiction. Antidepressants have been studied for their therapeutic potential to treat cocaine use disorder. Research has suggested that antidepressants attenuate both drug craving and the re-acquisition of drug-seeking and drug-taking behaviors. This study examined the efficacy of mirtazapine, an antidepressant/anxiolytic, in decreasing cocaine seeking in rats. We used the cocaine self-administration paradigm to assess the effects of mirtazapine on rats trained to self-administer cocaine or food under a fixed-ratio schedule. Mirtazapine (30 mg/kg, i.p.) was administered during extinction. Mirtazapine significantly attenuated non-reinforced lever-press responses during extinction. Moreover, the mirtazapine dosed for 30 days during extinction produced sustained attenuation of lever-press responses during re-acquisition of cocaine self-administration, without changing food-seeking behavior. Our results showed that mirtazapine attenuated the re-acquisition of cocaine-seeking responses. Our study pointed to the efficacy of mirtazapine in reducing the risk of drug relapse during abstinence, suggesting for its potential use as a novel pharmacological agent to treat drug abuse. Copyright © 2017 Elsevier Ltd. All rights reserved.

An attenuation correction method for PET/CT images

International Nuclear Information System (INIS)

Ue, Hidenori; Yamazaki, Tomohiro; Haneishi, Hideaki

2006-01-01

In PET/CT systems, accurate attenuation correction can be achieved by creating an attenuation map from an X-ray CT image. On the other hand, respiratory-gated PET acquisition is an effective method for avoiding motion blurring of the thoracic and abdominal organs caused by respiratory motion. In PET/CT systems employing respiratory-gated PET, using an X-ray CT image acquired during breath-holding for attenuation correction may have a large effect on the voxel values, especially in regions with substantial respiratory motion. In this report, we propose an attenuation correction method in which, as the first step, a set of respiratory-gated PET images is reconstructed without attenuation correction, as the second step, the motion of each phase PET image from the PET image in the same phase as the CT acquisition timing is estimated by the previously proposed method, as the third step, the CT image corresponding to each respiratory phase is generated from the original CT image by deformation according to the motion vector maps, and as the final step, attenuation correction using these CT images and reconstruction are performed. The effectiveness of the proposed method was evaluated using 4D-NCAT phantoms, and good stability of the voxel values near the diaphragm was observed. (author)

Therapeutic Potential of a Prolyl Hydroxylase Inhibitor FG-4592 for Parkinson’s Diseases in Vitro and in Vivo: Regulation of Redox Biology and Mitochondrial Function

Directory of Open Access Journals (Sweden)

Xuan Li

2018-04-01

Full Text Available As the main transcription factor that regulates the cellular responses to hypoxia, Hypoxia-inducible factor-1α (HIF-1α plays an important role in the pathogenesis of Parkinson’s disease (PD. HIF-1α is normally degraded through ubiquitination after hydroxylation by prolyl hydroxylases (PHD. Emerging evidence has suggested that HIF PHD inhibitors (HIF-PHI may have neuroprotective effects on PD through increasing HIF-1α levels. However, the therapeutic benefit of HIF-PHI for PD remains poorly explored due to the lack of proper clinical compounds and understanding of the underlying molecular mechanisms. In this study, we examined the therapeutic benefit of a new HIF-PHI, FG-4592, which is currently in phase 3 clinical trials to treat anemia in patients with chronic kidney diseases (CKD in PD models. FG-4592 attenuates MPP+ -induced apoptosis and loss of tyrosine hydroxylase (TH in SH-SY5Y cells. Pretreatment with FG-4592 mitigates MPP+-induced loss of mitochondrial membrane potential (MMP, mitochondrial oxygen consumption rate (OCR, production of reactive oxygen species (ROS and ATP. Furthermore, FG-4592 counterbalances the oxidative stress through up-regulating nuclear factor erythroid 2 p45-related factor 2 (Nrf-2, heme oxygenase-1 (HO-1 and superoxide dismutase 2 (SOD2. FG-4592 treatment also induces the expression of Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α through increasing the phosphorylation of AMP-activated protein kinase (AMPK. In MPTP-treated mice, FG-4592 protects against MPTP-induced loss of TH-positive neurons of substantia nigra and attenuates behavioral impairments. Collectively, our study demonstrates that FG-4592 is a promising therapeutic strategy for PD through improving the mitochondrial function under oxidative stress.

Josephson tunnel junction microwave attenuator

DEFF Research Database (Denmark)

Koshelets, V. P.; Shitov, S. V.; Shchukin, A. V.

1993-01-01

A new element for superconducting electronic circuitry-a variable attenuator-has been proposed, designed, and successfully tested. The principle of operation is based on the change in the microwave impedance of a superconductor-insulator-superconductor (SIS) Josephson tunnel junction when dc biased...... at different points in the current-voltage characteristic. Both numerical calculations based on the Tien-Gordon theory and 70-GHz microwave experiments have confirmed the wide dynamic range (more than 15-dB attenuation for one stage) and the low insertion loss in the ''open'' state. The performance of a fully...

Precision Model for Microwave Rotary Vane Attenuator

DEFF Research Database (Denmark)

Guldbrandsen, Tom

1979-01-01

A model for a rotary vane attenuator is developed to describe the attenuator reflection and transmission coefficients in detail. All the parameters of the model can be measured in situ, i.e., without diassembling any part. The tranmission errors caused by internal reflections are calculated from ...

Attenuation correction strategies for multi-energy photon emitters using SPECT

International Nuclear Information System (INIS)

Pretorius, P.H.; King, M.A.; Pan, T.S.

1996-01-01

The aim of this study was to investigate whether the photopeak window projections from different energy photons can be combined into a single window for reconstruction or if it is better to not combine the projections due to differences in the attenuation maps required for each photon energy. The mathematical cardiac torso (MCAT) phantom was modified to simulate the uptake of Ga-67 in the human body. Four spherical hot tumors were placed in locations which challenged attenuation correction. An analytical 3D projector with attenuation and detector response included was used to generate projection sets. Data were reconstructed using filtered backprojection (FBP) reconstruction with Butterworth filtering in conjunction with one iteration of Chang attenuation correction, and with 5 and 10 iterations of ordered-subset maximum-likelihood expectation-maximization reconstruction. To serve as a standard for comparison, the projection sets obtained from the two energies were first reconstructed separately using their own attenuation maps. The emission data obtained from both energies were added and reconstructed using the following attenuation strategies: (1) the 93 keV attenuation map for attenuation correction, (2) the 185 keV attenuation map for attenuation correction, (3) using a weighted mean obtained from combining the 93 keV and 185 keV maps, and (4) an ordered subset approach which combines both energies. The central count ratio (CCR) and total count ratio (TCR) were used to compare the performance of the different strategies. Compared to the standard method, results indicate an over-estimation with strategy 1, an under-estimation with strategy 2 and comparable results with strategies 3 and 4. In all strategies, the CCR's of sphere 4 were under-estimated, although TCR's were comparable to that of the other locations. The weighted mean and ordered subset strategies for attenuation correction were of comparable accuracy to reconstruction of the windows separately

Determination of mass attenuation coefficient in wood and leaves of typical trees by gamma-ray attenuation technique

International Nuclear Information System (INIS)

Miranda, Regina M. de; Pascholati, Elisabete M.

1997-01-01

Using an 241 Am source the mass attenuation coefficient of different woods and leaves of typical species of the Atlantic Forest were measured. The results for natural wood, dry wood and dry leaves indicate that the variation is very small among different species. However, woods present a higher attenuation than leaves, both depending on their water content. (author). 10 refs., 3 figs., 1 tab

Anomalies of ultrasound attenuation in metals under hydrostatic pressure

International Nuclear Information System (INIS)

Galkin, A.A.; Datsko, O.I.; Varyukhin, V.N.; Pilipenko, N.P.

1978-01-01

Ultrasonic attenuation was measured in polycrystal specimens of molybdenum, chromium and zinc under hydrostatic pressure up to 6 kbar. On the plot of ultrasound attenuation dependence on the pressure in molybdenum the maxima are observed under the pressure of 2 kbar. The anomaly of ultrasound attenuation is shown to connect only with brittle-ductile transtion

Post-Retrieval Extinction Attenuates Cocaine Memories

OpenAIRE

Sartor, Gregory C; Aston-Jones, Gary

2013-01-01

Recent studies have shown that post-retrieval extinction training attenuates fear and reward-related memories in both humans and rodents. This noninvasive, behavioral approach has the potential to be used in clinical settings to treat maladaptive memories that underlie several psychiatric disorders, including drug addiction. However, few studies to date have used a post-retrieval extinction approach to attenuate addiction-related memories. In the current study, we attempted to disrupt cocaine...

Spatially resolved ultrasonic attenuation in resistance spot welds: implications for nondestructive testing.

Science.gov (United States)

Mozurkewich, George; Ghaffari, Bita; Potter, Timothy J

2008-09-01

Spatial variation of ultrasonic attenuation and velocity has been measured in plane parallel specimens extracted from resistance spot welds. In a strong weld, attenuation is larger in the nugget than in the parent material, and the region of increased attenuation is surrounded by a ring of decreased attenuation. In the center of a stick weld, attenuation is even larger than in a strong weld, and the low-attenuation ring is absent. These spatial variations are interpreted in terms of differences in grain size and martensite formation. Measured frequency dependences indicate the presence of an additional attenuation mechanism besides grain scattering. The observed attenuations do not vary as commonly presumed with weld quality, suggesting that the common practice of using ultrasonic attenuation to indicate weld quality is not a reliable methodology.

Mapping Pn amplitude spreading and attenuation in Asia

Energy Technology Data Exchange (ETDEWEB)

Yang, Xiaoning [Los Alamos National Laboratory; Phillips, William S [Los Alamos National Laboratory; Stead, Richard J [Los Alamos National Laboratory

2010-12-06

Pn travels most of its path in the mantle lid. Mapping the lateral variation of Pn amplitude attenuation sheds light on material properties and dynamics of the uppermost region of the mantle. Pn amplitude variation depends on the wavefront geometric spreading as well as material attenuation. We investigated Pn geometric spreading, which is much more complex than a traditionally assumed power-law spreading model, using both synthetic and observed amplitude data collected in Asia. We derived a new Pn spreading model based on the formulation that was proposed previously to account for the spherical shape of the Earth (Yang et. al., BSSA, 2007). New parameters derived for the spreading model provide much better correction for Pn amplitudes in terms of residual behavior. Because we used observed Pn amplitudes to construct the model, the model incorporates not only the effect of the Earth's spherical shape, but also the effect of potential upper-mantle velocity gradients in the region. Using the new spreading model, we corrected Pn amplitudes measured at 1, 2, 4 and 6 Hz and conducted attenuation tomography. The resulting Pn attenuation model correlates well with the regional geology. We see high attenuation in regions such as northern Tibetan Plateau and the western Pacific subduction zone, and low attenuation for stable blocks such as Sichuan and Tarim basins.

A promising hybrid approach to SPECT attenuation correction

International Nuclear Information System (INIS)

Lewis, N.H.; Faber, T.L.; Corbett, J.R.; Stokely, E.M.

1984-01-01

Most methods for attenuation compensation in SPECT either rely on the assumption of uniform attenuation, or use slow iteration to achieve accuracy. However, hybrid methods that combine iteration with simple multiplicative correction can accommodate nonuniform attenuation, and such methods converge faster than other iterative techniques. The authors evaluated two such methods, which differ in use of a damping factor to control convergence. Both uniform and nonuniform attenuation were modeled, using simulated and phantom data for a rotating gamma camera. For simulations done with 360 0 data and the correct attenuation map, activity levels were reconstructed to within 5% of the correct values after one iteration. Using 180 0 data, reconstructed levels in regions representing lesion and background were within 5% of the correct values in three iterations; however, further iterations were needed to eliminate the characteristic streak artifacts. The damping factor had little effect on 360 0 reconstruction, but was needed for convergence with 180 0 data. For both cold- and hot-lesion models, image contrast was better from the hybrid methods than from the simpler geometric-mean corrector. Results from the hybrid methods were comparable to those obtained using the conjugate-gradient iterative method, but required 50-100% less reconstruction time. The relative speed of the hybrid methods, and their accuracy in reconstructing photon activity in the presence of nonuniform attenuation, make them promising tools for quantitative SPECT reconstruction

Facile N-oxygenation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by the flavin-containing monooxygenase. A convenient synthesis of tritiated [methyl-3H]-4-phenyl-2,3-dihydropyridinium species

International Nuclear Information System (INIS)

Cashman, J.R.

1988-01-01

A rapid, efficient procedure useful for the radiosynthesis of [Me- 3 H]-MPDP+ ([methyl- 3 H]-4-phenyl-2,3-dihydropyridinium species) is described. Hog liver microsomes or the highly purified flavin-containing monooxygenase from hog liver quantitatively biotransforms [Me- 3 H]-MPTP to its corresponding radiolabeled N-oxide. For the small-scale synthesis required for radiolabeling procedures, this enzymatic process is superior to H 2 O 2 -mediated N-oxygenation of MPTP. In the presence of 0.5 mM NADPH, 4.5 mM n-octylamine, and 2 microCi [Me- 3 H]-MPTP, the only product detected in extracts from incubations performed with hog liver microsomes or purified hog liver flavin-containing monooxygenase is [Me- 3 H]-MPTP N-oxide. [Me- 3 H]-MPTP N-oxide is almost completely converted to [Me- 3 H]-MPDP+ by the action of trifluoroacetic anhydride. This procedure has the advantage of using a commercially available tritiated starting material, efficient transformations, and easily accomplished purification to afford a rapid synthesis of [Me- 3 H]-MPDP+

Factors influencing seismic wave attenuation in the lithosphere in continental rift zones

Directory of Open Access Journals (Sweden)

А. А. Dobrynina

2017-01-01

Full Text Available Attenuation of seismic waves in the crust and the upper mantle has been studied in three global rift systems: the Baikal rift system (Eurasia, the North Tanzanian divergence zone (Africa and the Basin and Range Province (North America. Using the records of direct and coda waves of regional earthquakes, the single scattering theory [Aki, Chouet, 1975], the hybrid model from [Zeng, 1991] and the approach described in [Wennerberg, 1993], we estimated the seismic quality factor (QC, frequency parameter (n, attenuation coefficient (δ, and total attenuation (QT. In addition, we evaluated the contributions of two components into total attenuation: intrinsic attenuation (Qi, and scattering attenuation (Qsc. Values of QC are strongly dependent on the frequency within the range of 0.2–16 Hz, as well as on the length of the coda processing window. The observed increase of QC with larger lengths of the coda processing window can be interpreted as a decrease in attenuation with increasing depth. Having compared the depth variations in the attenuation coefficient (δ and the frequency (n with the velocity structures of the studied regions, we conclude that seismic wave attenuation changes at the velocity boundaries in the medium. Moreover, the comparison results show that the estimated variations in the attenuation parameters with increasing depth are considerably dependent on utilized velocity models of the medium. Lateral variations in attenuation of seismic waves correlate with the geological and geophysical characteristics of the regions, and attenuation is primarily dependent on the regional seismic activity and regional heat flow. The geological inhomogeneities of the medium and the age of crust consolidation are secondary factors. Our estimations of intrinsic attenuation (Qi and scattering attenuation (Qsc show that in all the three studied regions, intrinsic attenuation is the major contributor to total attenuation. Our study shows that the

A novel dual GLP-1 and GIP incretin receptor agonist is neuroprotective in a mouse model of Parkinson's disease by reducing chronic inflammation in the brain.

Science.gov (United States)

Cao, Lijun; Li, Dongfang; Feng, Peng; Li, Lin; Xue, Guo-Fang; Li, Guanglai; Hölscher, Christian

2016-04-13

The incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are growth factors. GLP-1 mimetics are on the market as treatments for type 2 diabetes. Both GLP-1 and GIP mimetics have shown neuroprotective properties in previous studies. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. Novel GLP-1/GIP dual-agonist peptides have been developed to treat diabetes. Here, we report the neuroprotective effects of a novel dual agonist (DA-JC1) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once daily (20 mg/kg intraperitoneally) for 7 days and the dual agonist was coinjected once daily (50 nmol/kg intraperitoneally). We found that the drug reduced most of the MPTP-induced motor impairments in the rotarod, open-field locomotion, and muscle strength test. The number of tyrosine hydroxylase-positive neurons in the substantia nigra and striatum was reduced by MPTP and increased by DA-JC1. Synapse numbers (synaptophysin expression) were reduced in the substantia nigra and the striatum by MPTP and DA-JC1 reversed this effect. The activation of a chronic inflammation response by MPTP was considerably reduced by the dual agonist (DA) (astroglia and microglia activation). Therefore, dual agonists show promise as a novel treatment of PD.

Earth-Space Link Attenuation Estimation via Ground Radar Kdp

Science.gov (United States)

Bolen, Steven M.; Benjamin, Andrew L.; Chandrasekar, V.

2003-01-01

A method of predicting attenuation on microwave Earth/spacecraft communication links, over wide areas and under various atmospheric conditions, has been developed. In the area around the ground station locations, a nearly horizontally aimed polarimetric S-band ground radar measures the specific differential phase (Kdp) along the Earth-space path. The specific attenuation along a path of interest is then computed by use of a theoretical model of the relationship between the measured S-band specific differential phase and the specific attenuation at the frequency to be used on the communication link. The model includes effects of rain, wet ice, and other forms of precipitation. The attenuation on the path of interest is then computed by integrating the specific attenuation over the length of the path. This method can be used to determine statistics of signal degradation on Earth/spacecraft communication links. It can also be used to obtain real-time estimates of attenuation along multiple Earth/spacecraft links that are parts of a communication network operating within the radar coverage area, thereby enabling better management of the network through appropriate dynamic routing along the best combination of links.

Determination of beta attenuation coefficients by means of timing method

International Nuclear Information System (INIS)

Ermis, E.E.; Celiktas, C.

2012-01-01

Highlights: ► Beta attenuation coefficients of absorber materials were found in this study. ► For this process, a new method (timing method) was suggested. ► The obtained beta attenuation coefficients were compatible with the results from the traditional one. ► The timing method can be used to determine beta attenuation coefficient. - Abstract: Using a counting system with plastic scintillation detector, beta linear and mass attenuation coefficients were determined for bakelite, Al, Fe and plexiglass absorbers by means of timing method. To show the accuracy and reliability of the obtained results through this method, the coefficients were also found via conventional energy method. Obtained beta attenuation coefficients from both methods were compared with each other and the literature values. Beta attenuation coefficients obtained through timing method were found to be compatible with the values obtained from conventional energy method and the literature.

Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore

Energy Technology Data Exchange (ETDEWEB)

Gharanei, M.; Hussain, A. [Department of Biomolecular and Sport Sciences, Coventry University, Cox Street, Coventry, CV1 5FB (United Kingdom); Janneh, O. [Department of Biomolecular and Sport Sciences, Coventry University, Cox Street, Coventry, CV1 5FB (United Kingdom); Pharmacology Research Laboratories, 70, Pembroke Place, The University of Liverpool, Liverpool. L69 3GF (United Kingdom); Maddock, H.L., E-mail: h.maddock@coventry.ac.uk [Department of Biomolecular and Sport Sciences, Coventry University, Cox Street, Coventry, CV1 5FB (United Kingdom)

2013-04-15

Chemotherapeutic agents such as doxorubicin are known to cause or exacerbate cardiovascular cell death when an underlying heart condition is present. However, the mechanism of doxorubicin-induced cardiotoxicity is unclear. Here we assess the cardiotoxic effects of doxorubicin in conditions of myocardial ischaemia reperfusion and the mechanistic basis of protection, in particular the role of the mitochondrial permeability transition pore (mPTP) in such protection. The effects of doxorubicin (1 μM) ± cyclosporine A (CsA, 0.2 μM; inhibits mPTP) were investigated in isolated male Sprague–Dawley rats using Langendorff heart and papillary muscle contraction models subjected to simulated ischaemia and reperfusion injury. Isolated rat cardiac myocytes were used in an oxidative stress model to study the effects of drug treatment on mPTP by confocal microscopy. Western blot analysis evaluated the effects of drug treatment on p-Akt and p-Erk 1/2 levels. Langendorff and the isometric contraction models showed a detrimental effect of doxorubicin throughout reperfusion/reoxygenation as well as increased p-Akt and p-Erk levels. Interestingly, CsA not only reversed the detrimental effects of doxorubicin, but also reduced p-Akt and p-Erk levels. In the sustained oxidative stress assay to study mPTP opening, doxorubicin decreased the time taken to depolarization and hypercontracture, but these effects were delayed in the presence of CsA. Collectively, our data suggest for the first that doxorubicin exacerbates myocardial injury in an ischaemia reperfusion model. If the inhibition of mPTP ameliorates the cardiotoxic effects of doxorubicin, then more selective inhibitors of mPTP should be further investigated for their utility in patients receiving doxorubicin. - Highlights: ► Doxorubicin exacerbates myocardial ischaemia reperfusion injury. ► Co-treatment with CsA protects against doxorubicin induced myocardial injury. ► CsA delays doxorubicin induced mPTP opening in laser

Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore

International Nuclear Information System (INIS)

Gharanei, M.; Hussain, A.; Janneh, O.; Maddock, H.L.

2013-01-01

Chemotherapeutic agents such as doxorubicin are known to cause or exacerbate cardiovascular cell death when an underlying heart condition is present. However, the mechanism of doxorubicin-induced cardiotoxicity is unclear. Here we assess the cardiotoxic effects of doxorubicin in conditions of myocardial ischaemia reperfusion and the mechanistic basis of protection, in particular the role of the mitochondrial permeability transition pore (mPTP) in such protection. The effects of doxorubicin (1 μM) ± cyclosporine A (CsA, 0.2 μM; inhibits mPTP) were investigated in isolated male Sprague–Dawley rats using Langendorff heart and papillary muscle contraction models subjected to simulated ischaemia and reperfusion injury. Isolated rat cardiac myocytes were used in an oxidative stress model to study the effects of drug treatment on mPTP by confocal microscopy. Western blot analysis evaluated the effects of drug treatment on p-Akt and p-Erk 1/2 levels. Langendorff and the isometric contraction models showed a detrimental effect of doxorubicin throughout reperfusion/reoxygenation as well as increased p-Akt and p-Erk levels. Interestingly, CsA not only reversed the detrimental effects of doxorubicin, but also reduced p-Akt and p-Erk levels. In the sustained oxidative stress assay to study mPTP opening, doxorubicin decreased the time taken to depolarization and hypercontracture, but these effects were delayed in the presence of CsA. Collectively, our data suggest for the first that doxorubicin exacerbates myocardial injury in an ischaemia reperfusion model. If the inhibition of mPTP ameliorates the cardiotoxic effects of doxorubicin, then more selective inhibitors of mPTP should be further investigated for their utility in patients receiving doxorubicin. - Highlights: ► Doxorubicin exacerbates myocardial ischaemia reperfusion injury. ► Co-treatment with CsA protects against doxorubicin induced myocardial injury. ► CsA delays doxorubicin induced mPTP opening in laser

Attenuated radon transform: theory and application in medicine and biology

Energy Technology Data Exchange (ETDEWEB)

Gullberg, G.T.

1979-06-01

A detailed analysis is given of the properties of the attenuated Radon transform and of how increases in photon attenuation influence the numerical accuracy and computation efficiency of iterative and convolution algorithms used to determine its inversion. The practical applications for this work involve quantitative assessment of the distribution of injected radiopharmaceuticals and radionuclides in man and animals for basic physiological and biochemical studies as well as clinical studies in nuclear medicine. A mathematical structure is developed using function theory and the theory of linear operators on Hilbert spaces which lends itself to better understanding the spectral properties of the attenuated Radon transform. The continuous attenuated Radon transform reduces to a matrix operator for discrete angular and lateral sampling, and the reconstruction problem reduces to a system of linear equations. For the situation of variable attenuation coefficient frequently found in nuclear medicine applications of imaging the heart and chest, the procedure developed in this thesis involves iterative techniques of performing the generalized inverse. For constant attenuation coefficient less than 0.15 cm/sup -1/, convolution methods can reliably reconstruct a 30 cm object with 0.5 cm resolution. However, for high attenuation coefficients or for the situation where there is variable attenuation such as reconstruction of distribution of isotopes in the heart, iterative techniques developed in this thesis give the best results. (ERB)

Attenuation of trace organic compounds (TOrCs) inbioelectrochemical systems

KAUST Repository

Werner, Craig M.

2015-04-01

Microbial fuel cells (MFCs) and microbial electrolysis cells (MECs) are two types of microbial bioelectrochemical systems (BESs) that use microorganisms to convert chemical energy in wastewaters into useful energy products such as (bio)electricity (MFC) or hydrogen gas (MEC). These two systems were evaluated for their capacity to attenuate trace organic compounds (TOrCs), commonly found in municipal wastewater, under closed circuit (current generation) and open circuit (no current generation) conditions, using acetate as the carbon source. A biocide was used to evaluate attenuation in terms of biotransformation versus sorption. The difference in attenuation observed before and after addition of the biocide represented biotransformation, while attenuation after addition of a biocide primarily indicated sorption. Attenuation of TOrCs was similar in MFCs and MECs for eight different TOrCs, except for caffeine and trimethoprim where slightly higher attenuation was observed in MECs. Electric current generation did not enhance attenuation of the TOrCs except for caffeine, which showed slightly higher attenuation under closed circuit conditions in both MFCs and MECs. Substantial sorption of the TOrCs occurred to the biofilm-covered electrodes, but no consistent trend could be identified regarding the physico-chemical properties of the TOrCs tested and the extent of sorption. The octanol-water distribution coefficient at pH 7.4 (log DpH 7.4) appeared to be a reasonable predictor for sorption of some of the compounds (carbamazepine, atrazine, tris(2-chloroethyl) phosphate and diphenhydramine) but not for others (N,N-Diethyl-meta-toluamide). Atenolol also showed high levels of sorption despite being the most hydrophilic in the suite of compounds studied (log DpH 7.4=-1.99). Though BESs do not show any inherent advantages over conventional wastewater treatment, with respect to TOrC removal, overall removals in BESs are similar to that reported for conventional wastewater

Active inference, sensory attenuation and illusions.

Science.gov (United States)

Brown, Harriet; Adams, Rick A; Parees, Isabel; Edwards, Mark; Friston, Karl

2013-11-01

Active inference provides a simple and neurobiologically plausible account of how action and perception are coupled in producing (Bayes) optimal behaviour. This can be seen most easily as minimising prediction error: we can either change our predictions to explain sensory input through perception. Alternatively, we can actively change sensory input to fulfil our predictions. In active inference, this action is mediated by classical reflex arcs that minimise proprioceptive prediction error created by descending proprioceptive predictions. However, this creates a conflict between action and perception; in that, self-generated movements require predictions to override the sensory evidence that one is not actually moving. However, ignoring sensory evidence means that externally generated sensations will not be perceived. Conversely, attending to (proprioceptive and somatosensory) sensations enables the detection of externally generated events but precludes generation of actions. This conflict can be resolved by attenuating the precision of sensory evidence during movement or, equivalently, attending away from the consequences of self-made acts. We propose that this Bayes optimal withdrawal of precise sensory evidence during movement is the cause of psychophysical sensory attenuation. Furthermore, it explains the force-matching illusion and reproduces empirical results almost exactly. Finally, if attenuation is removed, the force-matching illusion disappears and false (delusional) inferences about agency emerge. This is important, given the negative correlation between sensory attenuation and delusional beliefs in normal subjects--and the reduction in the magnitude of the illusion in schizophrenia. Active inference therefore links the neuromodulatory optimisation of precision to sensory attenuation and illusory phenomena during the attribution of agency in normal subjects. It also provides a functional account of deficits in syndromes characterised by false inference

Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress

Energy Technology Data Exchange (ETDEWEB)

Yu, Xiao-Jing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Jia, Lin-Lin; Qi, Jie; Song, Xin-Ai; Tan, Hong [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Cui, Wei [Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Chen, Wensheng [Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China)

2015-05-01

We hypothesized that chronic inhibition of NF-κB activity in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats (SHR). Young normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusions with NF–κB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN infusion of NF-κB inhibitor PDTC attenuated all these changes. These findings suggest that NF-κB activation in the PVN increases sympathoexcitation and hypertensive response, which are associated with the increases of PICs and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates PICs and oxidative stress in the PVN, thereby attenuates hypertension and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of NF-κB attenuates hypertension-induced cardiac hypertrophy. • PVN inhibition of NF-κB attenuates hypertension-induced neurohormonal excitation. • PVN inhibition of NF-κB attenuates hypertension-induced imbalance of cytokines

A practical attenuation compensation method for cone beam spect

International Nuclear Information System (INIS)

Manglos, S.H.; Jaszczak, R.J.; Floyd, C.E.; Greer, K.L.; Coleman, R.E.

1987-01-01

An algorithm for attenuation compensation of cone beam SPECT images has been developed and implemented. The algorithm is based on a multiplicative post-processing method previously used for parallel and fan beam geometries. This method computes the compensation from the estimated average attenuation of photons originating from each image pixel. In the present development, a uniform attenuation coefficient inside of the body contour is assumed, although the method could be extended to include a non-uniform attenuation map. The algorithm is tested with experimental projections of a phantom obtained using a cone beam collimator. Profiles through the reconstructed images are presented as a quantitative test of the improvement due to the compensation. The algorithm provides adequate compensation for attenuation in a simple uniform cylindrical phantom, and the computational time is short compared to that expected for iterative reconstruction techniques. Also observed are image distortions in some reconstructed slices when the source distribution extends beyond the edge of the cone beam axial field-of-view

Impact of Scattering Model on Disdrometer Derived Attenuation Scaling

Science.gov (United States)

Zemba, Michael; Luini, Lorenzo; Nessel, James; Riva, Carlo (Compiler)

2016-01-01

NASA Glenn Research Center (GRC), the Air Force Research Laboratory (AFRL), and the Politecnico di Milano (POLIMI) are currently entering the third year of a joint propagation study in Milan, Italy utilizing the 20 and 40 GHz beacons of the Alphasat TDP5 Aldo Paraboni scientific payload. The Ka- and Q-band beacon receivers were installed at the POLIMI campus in June of 2014 and provide direct measurements of signal attenuation at each frequency. Collocated weather instrumentation provides concurrent measurement of atmospheric conditions at the receiver; included among these weather instruments is a Thies Clima Laser Precipitation Monitor (optical disdrometer) which records droplet size distributions (DSD) and droplet velocity distributions (DVD) during precipitation events. This information can be used to derive the specific attenuation at frequencies of interest and thereby scale measured attenuation data from one frequency to another. Given the ability to both predict the 40 GHz attenuation from the disdrometer and the 20 GHz timeseries as well as to directly measure the 40 GHz attenuation with the beacon receiver, the Milan terminal is uniquely able to assess these scaling techniques and refine the methods used to infer attenuation from disdrometer data.In order to derive specific attenuation from the DSD, the forward scattering coefficient must be computed. In previous work, this has been done using the Mie scattering model, however, this assumes a spherical droplet shape. The primary goal of this analysis is to assess the impact of the scattering model and droplet shape on disdrometer derived attenuation predictions by comparing the use of the Mie scattering model to the use of the T-matrix method, which does not assume a spherical droplet. In particular, this paper will investigate the impact of these two scattering approaches on the error of the resulting predictions as well as on the relationship between prediction error and rain rate.

Patient position alters attenuation effects in multipinhole cardiac SPECT.

Science.gov (United States)

Timmins, Rachel; Ruddy, Terrence D; Wells, R Glenn

2015-03-01

Dedicated cardiac cameras offer improved sensitivity over conventional SPECT cameras. Sensitivity gains are obtained by large numbers of detectors and novel collimator arrangements such as an array of multiple pinholes that focus on the heart. Pinholes lead to variable amounts of attenuation as a source is moved within the camera field of view. This study evaluated the effects of this variable attenuation on myocardial SPECT images. Computer simulations were performed for a set of nine point sources distributed in the left ventricular wall (LV). Sources were placed at the location of the heart in both an anthropomorphic and a water-cylinder computer phantom. Sources were translated in x, y, and z by up to 5 cm from the center. Projections were simulated with and without attenuation and the changes in attenuation were compared. A LV with an inferior wall defect was also simulated in both phantoms over the same range of positions. Real camera data were acquired on a Discovery NM530c camera (GE Healthcare, Haifa, Israel) for five min in list-mode using an anthropomorphic phantom (DataSpectrum, Durham, NC) with 100 MBq of Tc-99m in the LV. Images were taken over the same range of positions as the simulations and were compared based on the summed perfusion score (SPS), defect width, and apparent defect uptake for each position. Point sources in the water phantom showed absolute changes in attenuation of ≤8% over the range of positions and relative changes of ≤5% compared to the apex. In the anthropomorphic computer simulations, absolute change increased to 20%. The changes in relative attenuation caused a change in SPS of position-dependent changes were removed with attenuation correction. Translation of a source relative to a multipinhole camera caused only small changes in homogeneous phantoms with SPS changing position-dependent changes in attenuation.

An Approximate Method for the Acoustic Attenuating VTI Eikonal Equation

KAUST Repository

Hao, Q.

2017-05-26

We present an approximate method to solve the acoustic eikonal equation for attenuating transversely isotropic media with a vertical symmetry axis (VTI). A perturbation method is used to derive the perturbation formula for complex-valued traveltimes. The application of Shanks transform further enhances the accuracy of approximation. We derive both analytical and numerical solutions to the acoustic eikonal equation. The analytic solution is valid for homogeneous VTI media with moderate anellipticity and strong attenuation and attenuation-anisotropy. The numerical solution is applicable for inhomogeneous attenuating VTI media.

An Approximate Method for the Acoustic Attenuating VTI Eikonal Equation

KAUST Repository

Hao, Q.; Alkhalifah, Tariq Ali

2017-01-01

We present an approximate method to solve the acoustic eikonal equation for attenuating transversely isotropic media with a vertical symmetry axis (VTI). A perturbation method is used to derive the perturbation formula for complex-valued traveltimes. The application of Shanks transform further enhances the accuracy of approximation. We derive both analytical and numerical solutions to the acoustic eikonal equation. The analytic solution is valid for homogeneous VTI media with moderate anellipticity and strong attenuation and attenuation-anisotropy. The numerical solution is applicable for inhomogeneous attenuating VTI media.

Po2 cycling protects diaphragm function during reoxygenation via ROS, Akt, ERK, and mitochondrial channels.

Science.gov (United States)

Zuo, Li; Pannell, Benjamin K; Re, Anthony T; Best, Thomas M; Wagner, Peter D

2015-12-01

Po2 cycling, often referred to as intermittent hypoxia, involves exposing tissues to brief cycles of low oxygen environments immediately followed by hyperoxic conditions. After experiencing long-term hypoxia, muscle can be damaged during the subsequent reintroduction of oxygen, which leads to muscle dysfunction via reperfusion injury. The protective effect and mechanism behind Po2 cycling in skeletal muscle during reoxygenation have yet to be fully elucidated. We hypothesize that Po2 cycling effectively increases muscle fatigue resistance through reactive oxygen species (ROS), protein kinase B (Akt), extracellular signal-regulated kinase (ERK), and certain mitochondrial channels during reoxygenation. Using a dihydrofluorescein fluorescent probe, we detected the production of ROS in mouse diaphragmatic skeletal muscle in real time under confocal microscopy. Muscles treated with Po2 cycling displayed significantly attenuated ROS levels (n = 5; P ROS, Akt, ERK, as well as chemical stimulators to close mitochondrial ATP-sensitive potassium channel (KATP) or open mitochondrial permeability transition pore (mPTP). All these blockers or stimulators abolished improved muscle function with Po2 cycling treatment. This current investigation has discovered a correlation between KATP and mPTP and the Po2 cycling pathway in diaphragmatic skeletal muscle. Thus we have identified a unique signaling pathway that may involve ROS, Akt, ERK, and mitochondrial channels responsible for Po2 cycling protection during reoxygenation conditions in the diaphragm. Copyright © 2015 the American Physiological Society.

When and Why Mimicry is Facilitated and Attenuated

NARCIS (Netherlands)

Stel, Mariëlle; van Dijk, Eric; van Baaren, Rick B.

2016-01-01

Although people tend to mimic others automatically, mimicry is facilitated or attenuated depending on the specific context. In the current paper, the authors discuss when mimicry is facilitated and attenuated depending on characteristics of situations, targets, and observers. On the basis of the

Magnitude corrections for attenuation in the upper mantle

International Nuclear Information System (INIS)

Anon.

1978-01-01

Since 1969, a consistent discrepancy in seismic magnitudes of nuclear detonations at NTS compared with magnitudes of detonations elsewhere in the world has been observed. This discrepancy can be explained in terms of a relatively high seismic attenuation for compressional waves in the upper mantle beneath the NTS and in certain other locations. A correction has been developed for this attenuation based on a relationship between the velocity of compressional waves at the top of the earth's mantle (just beneath the Mohorovicic discontinuity) and the seismic attenuation further down in the upper mantle. Our new definition of body-wave magnitude includes corrections for attenuation in the upper mantle at both ends of the teleseismic body-wave path. These corrections bring the NTS oservations into line with measurements of foreign events, and enable one to make more reliable estimates of yields of underground nuclear explosions, wherever the explosion occurs

Electromagnetic Wave Attenuation in Atmospheric Pressure Plasma

International Nuclear Information System (INIS)

Zhang Shu; Hu Xiwei; Liu Minghai; Luo Fang; Feng Zelong

2007-01-01

When an electromagnetic (EM) wave propagates in an atmospheric pressure plasma (APP) layer, its attenuation depends on the APP parameters such as the layer width, the electron density and its profile and collision frequency between electrons and neutrals. This paper proposes that a combined parameter-the product of the line average electron density n-bar and width d of the APP layer (i.e., the total number of electrons in a unit volume along the wave propagation path) can play a more explicit and decisive role in the wave attenuation than any of the above individual parameters does. The attenuation of the EM wave via the product of n-bar and d with various collision frequencies between electrons and neutrals is presented

Investigation of multilayered nanocomposites as low energy X-Rays attenuators

Energy Technology Data Exchange (ETDEWEB)

Silva, Liliane; Batista, Adriana S.M.; Nascimento, Jefferson P.; Furtado, Clascídia A.; Faria, Luiz O., E-mail: asfisica@gmail.com, E-mail: adriananuclear@yahoo.com.br, E-mail: farialo@cdtn.br, E-mail: nascimentopatricio@yahoo.com.br, E-mail: clas@cdtn.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

2017-11-01

The development of radiation attenuating materials has application in radioprotection and conditioning of short-lived waste. Polymeric materials can serve as a matrix for the dispersion of nanomaterials with good attenuation features, resulting in lightweight, conformable, flexible and easy-to-process materials. Thus, some well-known shielding materials could be used in low proportion for the formation of new materials. On the other hand, nanostructured carbon materials, such as graphene oxide (GO) and carbon nanotubes (NTCs), have been reported recently to show enhanced attenuation properties. In this sense, polymeric matrixes provide the necessary flexibility for use in various applications that require molding. For the present work, poly(vinylidene fluoride) [PVDF] homopolymers and its fluorinated copolymers were filled with nanosized metallic and graphene oxides in order to produce nanocomposites with increased low energy X-ray attenuation efficiency. Film samples of PVDF/reduced Graphene Oxide [PVDF/rGO] and Poly(vinylidene fluoride – tryfluorethylene)/Barium Oxide [P(VDF-TrFE)/BaO] were synthesized. In a second step, the samples were then sandwiched between Kapton® layers and exposed to X-rays source (8.5 keV). The samples were characterized with Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy (EDS). The attenuation coefficient was evaluated and compared with the attenuation of the individual constituents. It was observed an increase in the linear attenuation coefficient of the layered materials, justifying further investigation of these nanostructured composites as X-ray or gamma radiation attenuators. (author)

Investigation of multilayered nanocomposites as low energy X-Rays attenuators

International Nuclear Information System (INIS)

Silva, Liliane; Batista, Adriana S.M.; Nascimento, Jefferson P.; Furtado, Clascídia A.; Faria, Luiz O.

2017-01-01

The development of radiation attenuating materials has application in radioprotection and conditioning of short-lived waste. Polymeric materials can serve as a matrix for the dispersion of nanomaterials with good attenuation features, resulting in lightweight, conformable, flexible and easy-to-process materials. Thus, some well-known shielding materials could be used in low proportion for the formation of new materials. On the other hand, nanostructured carbon materials, such as graphene oxide (GO) and carbon nanotubes (NTCs), have been reported recently to show enhanced attenuation properties. In this sense, polymeric matrixes provide the necessary flexibility for use in various applications that require molding. For the present work, poly(vinylidene fluoride) [PVDF] homopolymers and its fluorinated copolymers were filled with nanosized metallic and graphene oxides in order to produce nanocomposites with increased low energy X-ray attenuation efficiency. Film samples of PVDF/reduced Graphene Oxide [PVDF/rGO] and Poly(vinylidene fluoride – tryfluorethylene)/Barium Oxide [P(VDF-TrFE)/BaO] were synthesized. In a second step, the samples were then sandwiched between Kapton® layers and exposed to X-rays source (8.5 keV). The samples were characterized with Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy (EDS). The attenuation coefficient was evaluated and compared with the attenuation of the individual constituents. It was observed an increase in the linear attenuation coefficient of the layered materials, justifying further investigation of these nanostructured composites as X-ray or gamma radiation attenuators. (author)

On the attenuation of the ambient seismic field

International Nuclear Information System (INIS)

Weemstra, C.

2013-01-01

Although myriad applications exploiting the ambient seismic field have been reported to date, comparatively little attention has been paid to its potential to resolve subsurface attenuation. The ambient seismic field, however, may ultimately prove itself an invaluable asset in constraining subsurface attenuation structure. Especially areas with dense seismometer coverage hold great potential. Moreover, since this coverage continues to grow, significant developments may await in the future. Subsurface structure in terms of attenuation is of great importance for many reasons. For example, knowledge of the attenuation structure may aid in predicting ground motions caused by future large earthquakes. From a scientific perspective, a great deal of new information may be extracted, potentially fostering research in related fields (e.g., geodynamics, hydrology). Both from an environmental and economic point of view, inversion of the ambient seismic wavefield for attenuation structure may in the future provide a means to image hydrocarbon reservoirs. In sufficiently diffuse wavefields, simple cross-correlation of long noise time series recorded by two receivers results in the response at one of the receivers as if there was a source at the position of the other. I present a case study that shows that thus retrieved surface waves can be used to recover attenuation beneath an array of ocean-bottom seismometers. Given the small aperture of the seismic survey, this is unprecedented. Unambiguous interpretation of recovered attenuation values is of major importance. Lack of understanding of the effect that preprocessing has on the amplitude of the noise cross-correlation prevents such unambiguous interpretation. I carefully examine the effect spectral whitening has on the noise cross-correlation. Emphasis is given to the dependence of the amplitudes on the length of the time windows employed in the cross-correlation procedure. Short time-window lengths may require an additional

Patient position alters attenuation effects in multipinhole cardiac SPECT

International Nuclear Information System (INIS)

Timmins, Rachel; Ruddy, Terrence D.; Wells, R. Glenn

2015-01-01

Purpose: Dedicated cardiac cameras offer improved sensitivity over conventional SPECT cameras. Sensitivity gains are obtained by large numbers of detectors and novel collimator arrangements such as an array of multiple pinholes that focus on the heart. Pinholes lead to variable amounts of attenuation as a source is moved within the camera field of view. This study evaluated the effects of this variable attenuation on myocardial SPECT images. Methods: Computer simulations were performed for a set of nine point sources distributed in the left ventricular wall (LV). Sources were placed at the location of the heart in both an anthropomorphic and a water-cylinder computer phantom. Sources were translated in x, y, and z by up to 5 cm from the center. Projections were simulated with and without attenuation and the changes in attenuation were compared. A LV with an inferior wall defect was also simulated in both phantoms over the same range of positions. Real camera data were acquired on a Discovery NM530c camera (GE Healthcare, Haifa, Israel) for five min in list-mode using an anthropomorphic phantom (DataSpectrum, Durham, NC) with 100 MBq of Tc-99m in the LV. Images were taken over the same range of positions as the simulations and were compared based on the summed perfusion score (SPS), defect width, and apparent defect uptake for each position. Results: Point sources in the water phantom showed absolute changes in attenuation of ≤8% over the range of positions and relative changes of ≤5% compared to the apex. In the anthropomorphic computer simulations, absolute change increased to 20%. The changes in relative attenuation caused a change in SPS of <1.5 for the water phantom but up to 4.2 in the anthropomorphic phantom. Changes were larger for axial than for transverse translations. These results were supported by SPS changes of up to six seen in the physical anthropomorphic phantom for axial translations. Defect width was also seen to significantly increase. The

An Analytical-empirical Calculation of Linear Attenuation Coefficient of Megavoltage Photon Beams.

Science.gov (United States)

Seif, F; Tahmasebi-Birgani, M J; Bayatiani, M R

2017-09-01

In this study, a method for linear attenuation coefficient calculation was introduced. Linear attenuation coefficient was calculated with a new method that base on the physics of interaction of photon with matter, mathematical calculation and x-ray spectrum consideration. The calculation was done for Cerrobend as a common radiotherapy modifier and Mercury. The values of calculated linear attenuation coefficient with this new method are in acceptable range. Also, the linear attenuation coefficient decreases slightly as the thickness of attenuating filter (Cerrobend or mercury) increased, so the procedure of linear attenuation coefficient variation is in agreement with other documents. The results showed that the attenuation ability of mercury was about 1.44 times more than Cerrobend. The method that was introduced in this study for linear attenuation coefficient calculation is general enough to treat beam modifiers with any shape or material by using the same formalism; however, calculating was made only for mercury and Cerrobend attenuator. On the other hand, it seems that this method is suitable for high energy shields or protector designing.

MNAtoolbox: A Monitored Natural Attenuation Site Screening Program

Energy Technology Data Exchange (ETDEWEB)

Borns, David J.; Brady, Patrick V.; Brady, Warren D.; Krupka, Kenneth M.; Spalding, Brian P.; Waters, Robert D.; Zhang, Pengchu

1999-07-12

Screening of sites for the potential application and reliance upon monitored natural attenuation (MNA) can be done using MNAtoolbox, a web-based tool for estimating extent of biodegradation, chemical transformation, and dilution. MNAtoolbox uses site-specific input data, where available (default parameters are taken from the literature), to roughly quantify the nature and extent of attenuation at a particular site. Use of MNAtoolbox provides 3 important elements of site evaluation: (1) Identifies likely attenuation pathways, (2) Clearly identifies sites where MNA is inappropriate, and (3) Evaluates data requirements for subsequent reliance on MNA as a sole or partial corrective action.

Deconvolution based attenuation correction for time-of-flight positron emission tomography

Science.gov (United States)

Lee, Nam-Yong

2017-10-01

For an accurate quantitative reconstruction of the radioactive tracer distribution in positron emission tomography (PET), we need to take into account the attenuation of the photons by the tissues. For this purpose, we propose an attenuation correction method for the case when a direct measurement of the attenuation distribution in the tissues is not available. The proposed method can determine the attenuation factor up to a constant multiple by exploiting the consistency condition that the exact deconvolution of noise-free time-of-flight (TOF) sinogram must satisfy. Simulation studies shows that the proposed method corrects attenuation artifacts quite accurately for TOF sinograms of a wide range of temporal resolutions and noise levels, and improves the image reconstruction for TOF sinograms of higher temporal resolutions by providing more accurate attenuation correction.

Shock wave attenuation in a micro-channel

Science.gov (United States)

Giordano, J.; Perrier, P.; Meister, L.; Brouillette, M.

2018-05-01

This work presents optical measurements of shock wave attenuation in a glass micro-channel. This transparent facility, with a cross section ranging from 1 mm× 150 μm to 1 mm× 500 μm, allowed for the use of high-speed schlieren videography to visualize the propagation of a shock wave within the entire micro-channel and to quantify velocity attenuation of the wave due to wall effects. In this paper, we present the experimental technique and the relevant data treatment we have used to increase the sensitivity of shock wave detection. Then, we compared our experimental results for different channel widths, lengths, and shock wave velocities with the analytical model for shock attenuation proposed by Russell (J Fluid Mech 27(2):305-314, 1967), which assumes laminar flow, and by Mirels (Attenuation in a shock tube due to unsteady-boundary-layer action, NACA Report 1333, 1957) for turbulent flow. We found that these models are inadequate to predict the observed data, owing to the presence of fully developed flow which violates the basic assumption of these models. The data are also compared with the empirical shock attenuation models proposed by Zeitoun (Phys Fluids 27(1):011701, 2015) and Deshpande and Puranik (Shock Waves 26(4):465-475, 2016), where better agreement is observed. Finally, we presented experimental data for the flow field behind the shock wave from measurements of the Mach wave angle which shows globally decreasing flow Mach numbers due to viscous wall effects.

Cement-based materials' characterization using ultrasonic attenuation

Science.gov (United States)

Punurai, Wonsiri

The quantitative nondestructive evaluation (NDE) of cement-based materials is a critical area of research that is leading to advances in the health monitoring and condition assessment of the civil infrastructure. Ultrasonic NDE has been implemented with varying levels of success to characterize cement-based materials with complex microstructure and damage. A major issue with the application of ultrasonic techniques to characterize cement-based materials is their inherent inhomogeneity at multiple length scales. Ultrasonic waves propagating in these materials exhibit a high degree of attenuation losses, making quantitative interpretations difficult. Physically, these attenuation losses are a combination of internal friction in a viscoelastic material (ultrasonic absorption), and the scattering losses due to the material heterogeneity. The objective of this research is to use ultrasonic attenuation to characterize the microstructure of heterogeneous cement-based materials. The study considers a real, but simplified cement-based material, cement paste---a common bonding matrix of all cement-based composites. Cement paste consists of Portland cement and water but does not include aggregates. First, this research presents the findings of a theoretical study that uses a set of existing acoustics models to quantify the scattered ultrasonic wavefield from a known distribution of entrained air voids. These attenuation results are then coupled with experimental measurements to develop an inversion procedure that directly predicts the size and volume fraction of entrained air voids in a cement paste specimen. Optical studies verify the accuracy of the proposed inversion scheme. These results demonstrate the effectiveness of using attenuation to measure the average size, volume fraction of entrained air voids and the existence of additional larger entrapped air voids in hardened cement paste. Finally, coherent and diffuse ultrasonic waves are used to develop a direct

[The role of mitochondrial permeability transition pore in the occurrence of septic myocardial depression].

Science.gov (United States)

Jin, Shanzi; Wang, Sheng

2016-08-01

Sepsis is defined as life-threatening organ dysfunction caused by a dys-regulated host response to infection and septic myocardial depression (SMD) is a common complication. Pathogenesis of SMD is complicated and there is lack of specific treatment. Mitochondrial damage is an important pathological basis of SMD, and mitochondrial permeability transition pore (MPTP) plays an important role in maintaining the normal structure and function of the mitochondria. The change of MPTP during sepsis is summarized in this review so as to reveal the significant mechanism of MPTP in the occurrence of SMD.

The use of microperforated plates to attenuate cavity resonances

DEFF Research Database (Denmark)

Fenech, Benjamin; Keith, Graeme; Jacobsen, Finn

2006-01-01

The use of microperforated plates to introduce damping in a closed cavity is examined. By placing a microperforated plate well inside the cavity instead of near a wall as traditionally done in room acoustics, high attenuation can be obtained for specific acoustic modes, compared with the lower...... attenuation that can be obtained in a broad frequency range with the conventional position of the plate. An analytical method for predicting the attenuation is presented. The method involves finding complex eigenvalues and eigenfunctions for the modified cavity and makes it possible to predict Green......'s functions. The results, which are validated experimentally, show that a microperforated plate can provide substantial attenuation of modes in a cavity. One possible application of these findings is the treatment of boiler tones in heat-exchanger cavities....

Fuzzy clustering-based segmented attenuation correction in whole-body PET

CERN Document Server

Zaidi, H; Boudraa, A; Slosman, DO

2001-01-01

Segmented-based attenuation correction is now a widely accepted technique to reduce noise contribution of measured attenuation correction. In this paper, we present a new method for segmenting transmission images in positron emission tomography. This reduces the noise on the correction maps while still correcting for differing attenuation coefficients of specific tissues. Based on the Fuzzy C-Means (FCM) algorithm, the method segments the PET transmission images into a given number of clusters to extract specific areas of differing attenuation such as air, the lungs and soft tissue, preceded by a median filtering procedure. The reconstructed transmission image voxels are therefore segmented into populations of uniform attenuation based on the human anatomy. The clustering procedure starts with an over-specified number of clusters followed by a merging process to group clusters with similar properties and remove some undesired substructures using anatomical knowledge. The method is unsupervised, adaptive and a...

Eicosapentaenoic acid (EPA) induced apoptosis in HepG2 cells through ROS–Ca{sup 2+}–JNK mitochondrial pathways

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yuanyuan; Han, Lirong [Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin 300457 (China); Qi, Wentao [Academy of State Administration of Grain, No.11 Baiwanzhuang Avenue, Xicheng District, Beijing, 100037 (China); Cheng, Dai; Ma, Xiaolei; Hou, Lihua [Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin 300457 (China); Cao, Xiaohong, E-mail: caoxh@tust.edu.cn [Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin 300457 (China); Wang, Chunling, E-mail: wangchunling@tust.edu.cn [Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin 300457 (China)

2015-01-24

Highlights: • EPA evoked ROS formation, [Ca{sup 2+}]{sub c} accumulation, the opening of MPTP and the phosphorylation of JNK. • EPA-induced [Ca{sup 2+}]{sub c} elevation was depended on production of ROS. • EPA-induced ROS generation, [Ca{sup 2+}]{sub c} increase, and JNK activated caused MPTP opening. • The apoptosis induced by EPA was related to release of cytochrome C through the MPTP. • EPA induced HepG2 cells apoptosis through ROS–Ca{sup 2+}–JNK mitochondrial pathways. - Abstract: Eicosapentaenoic acid (EPA), a well-known dietary n−3 PUFAS, has been considered to inhibit proliferation of tumor cells. However, the molecular mechanism related to EPA-induced liver cancer cells apoptosis has not been reported. In this study, we investigated the effect of EPA on HepG2 cells proliferation and apoptosis mechanism through mitochondrial pathways. EPA inhibited proliferation of HepG2 cells in a dose-dependent manner and had no significant effect on the cell viability of humor normal liver L-02 cells. It was found that EPA initially evoked ROS formation, leading to [Ca{sup 2+}]{sub c} accumulation and the mitochondrial permeability transition pore (MPTP) opening; EPA-induced HepG2 cells apoptosis was inhibited by N-acetylcysteine (NAC, an inhibitor of ROS), 1,2-bis (2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid (BAPTA-AM, a chelator of calcium) and CsA (inhibitor of MPTP). The relationship between ROS production, the increase of cytoplasmic Ca and MPTP opening was detected. It seems that ROS may act as an upstream regulator of EPA-induced [Ca{sup 2+}]{sub c} generation, moreover, generation of ROS, overload of mitochondrial [Ca{sup 2+}]{sub c}, and JNK activated cause the opening of MPTP. Western blotting results showed that EPA elevated the phosphorylation status of JNK, processes associated with the ROS generation. Simultaneously, the apoptosis induced by EPA was related to release of cytochrome C from mitochondria to cytoplasm through the MPTP

Investigation of photon attenuation coefficients for marble

International Nuclear Information System (INIS)

Basyigit, C; Akkurt, I; Kilincarslan, S; Akkurt, A

2005-01-01

The total linear attenuation coefficients μ (cm -1 ) have been obtained using the XCOM program at photon energies of 1 keV to 1 GeV for six different natural marbles produced in different places in Turkey. The individual contribution of photon interaction processes to the total linear attenuation coefficients for marble has been investigated. The calculated results were also compared with the measurements. The results obtained for marble were also compared with concrete. (note)

Empirical Relations for Optical Attenuation Prediction from Liquid Water Content of Fog

Directory of Open Access Journals (Sweden)

M. S. Khan

2012-09-01

Full Text Available Simultaneous measurements of the liquid water content (LWC and optical attenuation have been analyzed to predict optical attenuation caused by fog particles. Attenuation has been measured at two different wavelengths, 830 nm and 1550 nm, across co-located links. Five months measured data have been processed to assess power-law empirical models, which estimate optical attenuation from the LWC. The proposed models are compared with other published models and are demonstrated to perform sufficiently well to predict optical attenuation if the LWC values are available.

SEISMIC ATTENUATION FOR RESERVOIR CHARACTERIZATION

Energy Technology Data Exchange (ETDEWEB)

Joel Walls; M.T. Taner; Gary Mavko; Jack Dvorkin

2002-01-01

In Section 1 of this first report we will describe the work we are doing to collect and analyze rock physics data for the purpose of modeling seismic attenuation from other measurable quantities such as porosity, water saturation, clay content and net stress. This work and other empirical methods to be presented later, will form the basis for ''Q pseudo-well modeling'' that is a key part of this project. In Section 2 of this report, we will show the fundamentals of a new method to extract Q, dispersion, and attenuation from field seismic data. The method is called Gabor-Morlet time-frequency decomposition. This technique has a number of advantages including greater stability and better time resolution than spectral ratio methods.

Practical method of breast attenuation correction for cardiac SPECT

International Nuclear Information System (INIS)

Oliveira, Anderson de; Nogueira, Tindyua; Gutterres, Ricardo Fraga; Megueriam, Berdj Aram; Santos, Goncalo Rodrigues dos

2007-01-01

The breast attenuation effects on SPECT (Single Photon Emission Tomography) myocardium perfusion procedures have been lately scope of continuous inquiry. The requested attenuation correction factors are usually achieved by transmission analysis, making up the exposure of a standard external source to the SPECT, as a routine step. However, its high cost makes this methodology not fully available to the most of nuclear medicines services in Brazil and abroad. To overcome the problem, a new trend is presented in this work, implementing computational models to balance the breast attenuation effects on the left ventricle anterior wall, during myocardium perfusion scintigraphy procedures with SPECT. A neural network was put on in order to provide the attenuation correction indexes, based upon the following patients individual biotypes features: mass, age, height, chest and breast thicknesses, heart size, as well as the imparted activity intake levels. (author)

Practical method of breast attenuation correction for cardiac SPECT

Energy Technology Data Exchange (ETDEWEB)

Oliveira, Anderson de; Nogueira, Tindyua; Gutterres, Ricardo Fraga [Comissao Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil). Coordenacao Geral de Instalacoes Medicas e Industriais (CGMI)]. E-mails: anderson@cnen.gov.br; tnogueira@cnen.gov.br; rguterre@cnen.gov.br; Megueriam, Berdj Aram [Instituto Nacional do Cancer (INCA), Rio de Janeiro, RJ (Brazil)]. E-mail: megueriam@hotmail.com; Santos, Goncalo Rodrigues dos [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil)]. E-mail: goncalo@cnen.gov.br

2007-07-01

The breast attenuation effects on SPECT (Single Photon Emission Tomography) myocardium perfusion procedures have been lately scope of continuous inquiry. The requested attenuation correction factors are usually achieved by transmission analysis, making up the exposure of a standard external source to the SPECT, as a routine step. However, its high cost makes this methodology not fully available to the most of nuclear medicines services in Brazil and abroad. To overcome the problem, a new trend is presented in this work, implementing computational models to balance the breast attenuation effects on the left ventricle anterior wall, during myocardium perfusion scintigraphy procedures with SPECT. A neural network was put on in order to provide the attenuation correction indexes, based upon the following patients individual biotypes features: mass, age, height, chest and breast thicknesses, heart size, as well as the imparted activity intake levels. (author)

Restorative effect of endurance exercise on behavioral deficits in the chronic mouse model of Parkinson's disease with severe neurodegeneration.

Science.gov (United States)

Pothakos, Konstantinos; Kurz, Max J; Lau, Yuen-Sum

2009-01-20

Animal models of Parkinson's disease have been widely used for investigating the mechanisms of neurodegenerative process and for discovering alternative strategies for treating the disease. Following 10 injections with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 25 mg/kg) and probenecid (250 mg/kg) over 5 weeks in mice, we have established and characterized a chronic mouse model of Parkinson's disease (MPD), which displays severe long-term neurological and pathological defects resembling that of the human Parkinson's disease in the advanced stage. The behavioral manifestations in this chronic mouse model of Parkinson's syndrome remain uninvestigated. The health benefit of exercise in aging and in neurodegenerative disorders including the Parkinson's disease has been implicated; however, clinical and laboratory studies in this area are limited. In this research with the chronic MPD, we first conducted a series of behavioral tests and then investigated the impact of endurance exercise on the identified Parkinsonian behavioral deficits. We report here that the severe chronic MPD mice showed significant deficits in their gait pattern consistency and in learning the cued version of the Morris water maze. Their performances on the challenging beam and walking grid were considerably attenuated suggesting the lack of balance and motor coordination. Furthermore, their spontaneous and amphetamine-stimulated locomotor activities in the open field were significantly suppressed. The behavioral deficits in the chronic MPD lasted for at least 8 weeks after MPTP/probenecid treatment. When the chronic MPD mice were exercise-trained on a motorized treadmill 1 week before, 5 weeks during, and 8-12 weeks after MPTP/probenecid treatment, the behavioral deficits in gait pattern, spontaneous ambulatory movement, and balance performance were reversed; whereas neuronal loss and impairment in cognitive skill, motor coordination, and amphetamine-stimulated locomotor activity were not

Attenuation correction for the NIH ATLAS small animal PET scanner

CERN Document Server

Yao, Rutao; Liow, JeihSan; Seidel, Jurgen

2003-01-01

We evaluated two methods of attenuation correction for the NIH ATLAS small animal PET scanner: 1) a CT-based method that derives 511 keV attenuation coefficients (mu) by extrapolation from spatially registered CT images; and 2) an analytic method based on the body outline of emission images and an empirical mu. A specially fabricated attenuation calibration phantom with cylindrical inserts that mimic different body tissues was used to derive the relationship to convert CT values to (I for PET. The methods were applied to three test data sets: 1) a uniform cylinder phantom, 2) the attenuation calibration phantom, and 3) a mouse injected with left bracket **1**8F right bracket FDG. The CT-based attenuation correction factors were larger in non-uniform regions of the imaging subject, e.g. mouse head, than the analytic method. The two methods had similar correction factors for regions with uniform density and detectable emission source distributions.

Acousto-optic measurements of ultrasound attenuation in tellurium dioxide crystal

International Nuclear Information System (INIS)

Voloshinov, V. B.; Lemyaskina, E. A.

1996-01-01

The paper is devoted to experimental investigation of ultrasound propagation in tellurium dioxide monocrystal. In particular, attenuation of slow shear acoustic modes in the crystal was measured. The measurements were performed by acousto-optic methods using probing of acoustic column by a laser beam. The paper describes measurements of acoustic attenuation coefficient for slow shear ultrasonic waves propagating at an angle =4.5 O with respect to the (110) direction in the (110) plane. The investigation was made at acoustic frequency f = 100 MHz with pulsed acoustic waves and with an optical beam of a He-Ne laser. It is found that the attenuation coefficient is α = 0.57 cm -1 ± 15 %. The attenuation at acoustic frequencies f ≥ 100 MHz influences performance characteristics of acousto-optical devices based on tellurium dioxide. As proved, spectral resolution of a quasicollinear acoustooptic filter decreases by a factor of 2 compared to a case of the attenuation absence. (authors)

Lattice Boltzmann simulations of attenuation-driven acoustic streaming

International Nuclear Information System (INIS)

Haydock, David; Yeomans, J M

2003-01-01

We show that lattice Boltzmann simulations can be used to model the attenuation-driven acoustic streaming produced by a travelling wave. Comparisons are made to analytical results and to the streaming pattern produced by an imposed body force approximating the Reynolds stresses. We predict the streaming patterns around a porous material in an attenuating acoustic field

Wave attenuation across a tidal marsh in San Francisco Bay

Science.gov (United States)

Foster-Martinez, Madeline R.; Lacy, Jessica; Ferner, Matthew C.; Variano, Evan A.

2018-01-01

Wave attenuation is a central process in the mechanics of a healthy salt marsh. Understanding how wave attenuation varies with vegetation and hydrodynamic conditions informs models of other marsh processes that are a function of wave energy (e.g. sediment transport) and allows for the incorporation of marshes into coastal protection plans. Here, we examine the evolution of wave height across a tidal salt marsh in San Francisco Bay. Instruments were deployed along a cross-shore transect, starting on the mudflat and crossing through zones dominated by Spartina foliosa and Salicornia pacifica. This dataset is the first to quantify wave attenuation for these vegetation species, which are abundant in the intertidal zone of California estuaries. Measurements were collected in the summer and winter to assess seasonal variation in wave attenuation. Calculated drag coefficients of S. foliosa and S. pacifica were similar, indicating equal amounts of vegetation would lead to similar energy dissipation; however, S. pacifica has much greater biomass close to the bed (<20 cm) and retains biomass throughout the year, and therefore, it causes more total attenuation. S. foliosa dies back in the winter, and waves often grow across this section of the marsh. For both vegetation types, attenuation was greatest for low water depths, when the vegetation was emergent. For both seasons, attenuation rates across S. pacifica were the highest and were greater than published attenuation rates across similar (Spartina alterniflora) salt marshes for the comparable depths. These results can inform designs for marsh restorations and management plans in San Francisco Bay and other estuaries containing these species.

Adaptive attenuation of aliased ground roll using the shearlet transform

Science.gov (United States)

Hosseini, Seyed Abolfazl; Javaherian, Abdolrahim; Hassani, Hossien; Torabi, Siyavash; Sadri, Maryam

2015-01-01

Attenuation of ground roll is an essential step in seismic data processing. Spatial aliasing of the ground roll may cause the overlap of the ground roll with reflections in the f-k domain. The shearlet transform is a directional and multidimensional transform that separates the events with different dips and generates subimages in different scales and directions. In this study, the shearlet transform was used adaptively to attenuate aliased and non-aliased ground roll. After defining a filtering zone, an input shot record is divided into segments. Each segment overlaps adjacent segments. To apply the shearlet transform on each segment, the subimages containing aliased and non-aliased ground roll, the locations of these events on each subimage are selected adaptively. Based on these locations, mute is applied on the selected subimages. The filtered segments are merged together, using the Hanning function, after applying the inverse shearlet transform. This adaptive process of ground roll attenuation was tested on synthetic data, and field shot records from west of Iran. Analysis of the results using the f-k spectra revealed that the non-aliased and most of the aliased ground roll were attenuated using the proposed adaptive attenuation procedure. Also, we applied this method on shot records of a 2D land survey, and the data sets before and after ground roll attenuation were stacked and compared. The stacked section after ground roll attenuation contained less linear ground roll noise and more continuous reflections in comparison with the stacked section before the ground roll attenuation. The proposed method has some drawbacks such as more run time in comparison with traditional methods such as f-k filtering and reduced performance when the dip and frequency content of aliased ground roll are the same as those of the reflections.

Occurrence and in-stream attenuation of wastewater-derived pharmaceuticals in Iberian rivers.

Science.gov (United States)

Acuña, Vicenç; von Schiller, Daniel; García-Galán, Maria Jesús; Rodríguez-Mozaz, Sara; Corominas, Lluís; Petrovic, Mira; Poch, Manel; Barceló, Damià; Sabater, Sergi

2015-01-15

A multitude of pharmaceuticals enter surface waters via discharges of wastewater treatment plants (WWTPs), and many raise environmental and health concerns. Chemical fate models predict their concentrations using estimates of mass loading, dilution and in-stream attenuation. However, current comprehension of the attenuation rates remains a limiting factor for predictive models. We assessed in-stream attenuation of 75 pharmaceuticals in 4 river segments, aiming to characterize in-stream attenuation variability among different pharmaceutical compounds, as well as among river segments differing in environmental conditions. Our study revealed that in-stream attenuation was highly variable among pharmaceuticals and river segments and that none of the considered pharmaceutical physicochemical and molecular properties proved to be relevant in determining the mean attenuation rates. Instead, the octanol-water partition coefficient (Kow) influenced the variability of rates among river segments, likely due to its effect on sorption to sediments and suspended particles, and therefore influencing the balance between the different attenuation mechanisms (biotransformation, photolysis, sorption, and volatilization). The magnitude of the measured attenuation rates urges scientists to consider them as important as dilution when aiming to predict concentrations in freshwater ecosystems. Copyright © 2014 Elsevier B.V. All rights reserved.

Brain structural changes in cynomolgus monkeys administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A longitudinal voxel-based morphometry and diffusion tensor imaging study.

Science.gov (United States)

Jeong, Hyeonseok S; Lee, Sang-Rae; Kim, Jieun E; Lyoo, In Kyoon; Yoon, Sujung; Namgung, Eun; Chang, Kyu-Tae; Kim, Bom Sahn; Yang, Sejung; Im, Jooyeon J; Jeon, Saerom; Kang, Ilhyang; Ma, Jiyoung; Chung, Yong-An; Lim, Soo Mee

2018-01-01

In animal models of Parkinson's disease (PD), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is one of the most widely used agents that damages the nigrostriatal dopaminergic pathway. However, brain structural changes in response to MPTP remain unclear. This study aimed to investigate in vivo longitudinal changes in gray matter (GM) volume and white matter (WM) microstructure in primate models administered with MPTP. In six cynomolgus monkeys, high-resolution magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) scans were acquired 7 times over 32 weeks, and assessments of motor symptoms were conducted over 15 months, before and after the MPTP injection. Changes in GM volume and WM microstructure were estimated on a voxel-by-voxel basis. Mixed-effects regression models were used to examine the trajectories of these structural changes. GM volume initially increased after the MPTP injection and gradually decreased in the striatum, midbrain, and other dopaminergic areas. The cerebellar volume temporarily decreased and returned to its baseline level. The rate of midbrain volume increase was positively correlated with the increase rate of motor symptom severity (Spearman rho = 0.93, p = 0.008). Mean, axial, and radial diffusivity in the striatum and frontal areas demonstrated initial increases and subsequent decreases. The current multi-modal imaging study of MPTP-administered monkeys revealed widespread and dynamic structural changes not only in the nigrostriatal pathway but also in other cortical, subcortical, and cerebellar areas. Our findings may suggest the need to further investigate the roles of inflammatory reactions and glial activation as potential underlying mechanisms of these structural changes.

[Studies on the chemical constituents of Buddleja albiflora (II)].

Science.gov (United States)

Zhang, Hai-Ping; Tao, Liang

2010-06-01

To study the chemical constituents of Buddleja albiflora. The constituents were isolated by column chromatography and their structures were elucidated by spectroscopic analyses. seven compounds were isolated and identified as aucubin (1), catalpol (2), acteoside (3), martynoside (4), ursolicacid (5), daucosterol (6), beta-sitosterol-3-0-beta-D-(6'-0-palmitate) glucopyranosisde (7). All these compounds are obtained from Buddleja albiflora for the first time.

Characterizing X-ray Attenuation of Containerized Cargo

Energy Technology Data Exchange (ETDEWEB)

Birrer, N. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Divin, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Glenn, S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Martz, H. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Wang, G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2016-08-02

X-ray inspection systems can be used to detect radiological and nuclear threats in imported cargo. In order to better understand performance of these systems, the attenuation characteristics of imported cargo need to be determined. This project focused on developing image processing algorithms for segmenting cargo and using x-ray attenuation to quantify equivalent steel thickness to determine cargo density. These algorithms were applied to over 450 cargo radiographs. The results are summarized in this report.

Using Auditory Steady-State Responses for Measuring Hearing Protector Attenuation

Directory of Open Access Journals (Sweden)

Olivier Valentin

2017-01-01

Full Text Available Introduction: Present methods of measuring the attenuation of hearing protection devices (HPDs have limitations. Objective measurements such as field microphone in real-ear do not assess bone-conducted sound. Psychophysical measurements such as real-ear attenuation at threshold (REAT are biased due to the low frequency masking effects from test subjects’ physiological noise and the variability of measurements based on subjective responses. An auditory steady-state responses (ASSRs procedure is explored as a technique which might overcome these limitations. Subjects and Methods: Pure tone stimuli (500 and 1000 Hz, amplitude modulated at 40 Hz, are presented to 10 normal-hearing adults through headphones at three levels in 10 dB steps. Two conditions were assessed: unoccluded ear canal and occluded ear canal. ASSR amplitude data as a function of the stimulation level are linearized using least-square regressions. The “physiological attenuation” is then calculated as the average difference between the two measurements. The technical feasibility of measuring earplug attenuation is demonstrated for the group average attenuation across subjects. Results: No significant statistical difference is found between the average REAT attenuation and the average ASSR-based attenuation. Conclusion: Feasibility is not yet demonstrated for individual subjects since differences between the estimates occurred for some subjects.

Analytical inversion formula for uniformly attenuated fan-beam projections

International Nuclear Information System (INIS)

Weng, Y.; Zeng, G.L.; Gullberg, G.T.

1997-01-01

In deriving algorithms to reconstruct single photon emission computed tomography (SPECT) projection data, it is important that the algorithm compensates for photon attenuation in order to obtain quantitative reconstruction results. A convolution backprojection algorithm was derived by Tretiak and Metz to reconstruct two-dimensional (2-D) transaxial slices from uniformly attenuated parallel-beam projections. Using transformation of coordinates, this algorithm can be modified to obtain a formulation useful to reconstruct uniformly attenuated fan-beam projections. Unlike that for parallel-beam projections, this formulation does not produce a filtered backprojection reconstruction algorithm but instead has a formulation that is an inverse integral operator with a spatially varying kernel. This algorithm thus requires more computation time than does the filtered backprojection reconstruction algorithm for the uniformly attenuated parallel-beam case. However, the fan-beam reconstructions demonstrate the same image quality as that of parallel-beam reconstructions

Gamma ray attenuation coefficient measurement for neutron-absorbent materials

International Nuclear Information System (INIS)

Jalali, Majid; Mohammadi, Ali

2008-01-01

The compounds Na 2 B 4 O 7 , H 3 BO 3 , CdCl 2 and NaCl and their solutions attenuate gamma rays in addition to neutron absorption. These compounds are widely used in the shielding of neutron sources, reactor control and neutron converters. Mass attenuation coefficients of gamma related to the four compounds aforementioned, in energies 662, 778.9, 867.38, 964.1, 1085.9, 1173, 1212.9, 1299.1,1332 and 1408 keV, have been determined by the γ rays transmission method in a good geometry setup; also, these coefficients were calculated by MCNP code. A comparison between experiments, simulations and Xcom code has shown that the study has potential application for determining the attenuation coefficient of various compound materials. Experiment and computation show that H 3 BO 3 with the lowest average Z has the highest gamma ray attenuation coefficient among the aforementioned compounds

Brunenders: a partially attenuated historic poliovirus type I vaccine strain.

Science.gov (United States)

Sanders, Barbara P; Liu, Ying; Brandjes, Alies; van Hoek, Vladimir; de Los Rios Oakes, Isabel; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

2015-09-01

Brunenders, a type I poliovirus (PV) strain, was developed in 1952 by J. F. Enders and colleagues through serial in vitro passaging of the parental Brunhilde strain, and was reported to display partial neuroattenuation in monkeys. This phenotype of attenuation encouraged two vaccine manufacturers to adopt Brunenders as the type I component for their inactivated poliovirus vaccines (IPVs) in the 1950s, although today no licensed IPV vaccine contains Brunenders. Here we confirmed, in a transgenic mouse model, the report of Enders on the reduced neurovirulence of Brunenders. Although dramatically neuroattenuated relative to WT PV strains, Brunenders remains more virulent than the attenuated oral vaccine strain, Sabin 1. Importantly, the neuroattenuation of Brunenders does not affect in vitro growth kinetics and in vitro antigenicity, which were similar to those of Mahoney, the conventional type I IPV vaccine strain. We showed, by full nucleotide sequencing, that Brunhilde and Brunenders differ at 31 nucleotides, eight of which lead to amino acid changes, all located in the capsid. Upon exchanging the Brunenders capsid sequence with that of the Mahoney capsid, WT neurovirulence was regained in vivo, suggesting a role for the capsid mutations in Brunenders attenuation. To date, as polio eradication draws closer, the switch to using attenuated strains for IPV is actively being pursued. Brunenders preceded this novel strategy as a partially attenuated IPV strain, accompanied by decades of successful use in the field. Providing data on the attenuation of Brunenders may be of value in the further construction of attenuated PV strains to support the grand pursuit of the global eradication of poliomyelitis.

Viability of natural attenuation in a petroleum-contaminated shallow sandy aquifer

International Nuclear Information System (INIS)

Lee, Jin-Yong; Lee, Kang-Kun

2003-01-01

More than 20 years would be required to clean up the site by natural attenuation alone. - This study focused on evaluating and quantifying the potential of natural attenuation of groundwater at a petroleum-contaminated site in an industrial area of a satellite city of Seoul, Korea. Groundwater at the study site was contaminated with toluene, ethylbenzene and xylene (TEX). Eight rounds of groundwater sampling and subsequent chemical analyses were performed over a period of 3 years. The groundwater quality data suggest that TEX concentrations at this site have been decreasing with time and that the TEX plume is at a quasi-steady state. Trend analysis, changes in mass flux and plume area also confirmed that the TEX plume has reached a quasi-steady state. The proportion of the total attenuation attributable to biodegradation has decreased over the monitoring period while contribution of other attenuation processes, such as dilution or dispersion, has increased. Based on the calculated attenuation rates, it would take more than 20 years to clean up the site by natural attenuation alone

Radiation-induced attenuation in integrated optical materials

International Nuclear Information System (INIS)

Evans, B.D.

1989-01-01

This paper reports that three materials commonly employed in opto-electronic integrated circuits evaluated for radiation-induced optical attenuation in the range 300 nm to 3000 nm. These include optically clear epoxy and crystalline lithium niobate after Co-60 exposure and crystalline tellurium dioxide after mixed gamma/fast-neutron exposure. In all these materials, however, induced loss was restricted to shorter wavelengths; attenuation induced at the telecommunications windows near 850, 1300 and 1550 nm was <0.1 dB/cm

Principles underlying rational design of live attenuated influenza vaccines

Science.gov (United States)

Jang, Yo Han

2012-01-01

Despite recent innovative advances in molecular virology and the developments of vaccines, influenza virus remains a serious burden for human health. Vaccination has been considered a primary countermeasure for prevention of influenza infection. Live attenuated influenza vaccines (LAIVs) are particularly attracting attention as an effective strategy due to several advantages over inactivated vaccines. Cold-adaptation, as a classical means for attenuating viral virulence, has been successfully used for generating safe and effective donor strains of LAIVs against seasonal epidemics and occasional pandemics. Recently, the advent of reverse genetics technique expedited a variety of rational strategies to broaden the pool of LAIVs. Considering the breadth of antigenic diversity of influenza virus, the pool of LAIVs is likely to equip us with better options for controlling influenza pandemics. With a brief reflection on classical attenuating strategies used at the initial stage of development of LAIVs, especially on the principles underlying the development of cold-adapted LAIVs, we further discuss and outline other attenuation strategies especially with respect to the rationales for attenuation, and their practicality for mass production. Finally, we propose important considerations for a rational vaccine design, which will provide us with practical guidelines for improving the safety and effectiveness of LAIVs. PMID:23596576

Cooperative effect of the attenuation determinants derived from poliovirus sabin 1 strain is essential for attenuation of enterovirus 71 in the NOD/SCID mouse infection model.

Science.gov (United States)

Arita, Minetaro; Ami, Yasushi; Wakita, Takaji; Shimizu, Hiroyuki

2008-02-01

Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and is also associated with serious neurological disorders. An attenuated EV71 strain [EV71(S1-3')] has been established in the cynomolgus monkey infection model; this strain contains the attenuation determinants derived from the type 1 poliovirus vaccine strain, Sabin 1 [PV1(Sabin)], in the 5' nontranslated region (NTR), 3D polymerase, and 3' NTR. In this study, we analyzed the effect of the attenuation determinants of PV1(Sabin) on EV71 infection in a NOD/SCID mouse infection model. We isolated a mouse-adapted EV71 strain [EV71(NOD/SCID)] that causes paralysis of the hind limbs in 3- to 4-week-old NOD/SCID mice by adaptation of the virulent EV71(Nagoya) strain in the brains of NOD/SCID mice. A single mutation at nucleotide 2876 that caused an amino acid change in capsid protein VP1 (change of the glycine at position 145 to glutamic acid) was essential for the mouse-adapted phenotype in NOD/SCID mice. Next, we introduced attenuation determinants derived from PV1(Sabin) along with the mouse adaptation mutation into the EV71(Nagoya) genome. In 4-week-old mice, the determinants in the 3D polymerase and 3' NTR, which are the major temperature-sensitive determinants, had a strong effect on attenuation. In contrast, the effect of individual determinants was weak in 3-week-old NOD/SCID mice, and all the determinants were required for substantial attenuation. These results suggest that a cooperative effect of the attenuation determinants of PV1(Sabin) is essential for attenuated neurovirulence of EV71.

Quantitative contrast-enhanced CT attenuation evaluation of osseous metastases following chemotherapy

Energy Technology Data Exchange (ETDEWEB)

Chang, Connie Y.; Simeone, F.J.; Torriani, Martin; Bredella, Miriam A. [Massachusetts General Hospital, Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Boston, MA (United States)

2017-10-15

Osseous metastases often undergo an osteoblastic healing response following chemotherapy. The purpose of our study was to demonstrate the quantitative CT changes in attenuation of osseous metastases before and after chemotherapy. Our study was IRB approved and HIPAA compliant. Our cohort consisted of 86 consecutive cancer patients with contrast-enhanced CTs before and 14 ± 2 (12-25) months after initiation of chemotherapy (60 ± 11 years, 36 males, 50 females). The average and maximum metastasis attenuations were measured in Hounsfield units (HU) by two readers. Treatment effects were assessed using paired t-tests and Fisher exact tests. Intraclass correlation coefficients (ICCs) were calculated. Patient records were reviewed to determine the patient's clinical status (worse, unchanged, or improved) at the time of follow-up CT. The distribution of lesion types was as follows: lytic (30/86, 35%), blastic (43/86, 50%), and mixed lytic-blastic (13/86, 15%). There was a significant increase in average and maximum CT attenuation of metastases following chemotherapy for all patients, which remained statistically significant when stratified by lesion type, clinical status (worsening or improving/stable), cancer type (breast, lung), and radiation therapy (P < 0.05). In a subgroup of patients whose osseous metastases decreased in average attenuation (14/86, 16%), more patients had a worse clinical status (11/14, 79%) (P = 0.02). ICC was almost perfect for average attenuation and substantial for maximum attenuation. Quantitative assessment of osseous metastatic disease using CT attenuation measurements demonstrated a statistically significant increase in attenuation more than 12 months after initiation of chemotherapy. (orig.)

Attenuation of the gamma rays in tissues

International Nuclear Information System (INIS)

Arcos P, A.; Rodriguez N, S.; Pinedo S, A.; Amador V, P.; Chacon R, A.; Vega C, H.R.

2005-01-01

The mass and lineal attenuation coefficient and of hepatic tissue, muscular, osseous and of brain before gamma rays of 10 -3 to 10 5 MeV were calculated. For the case of the osseous tissue the calculation was made for the cartilage, the cortical tissue and the bone marrow. During the calculations the elementary composition of the tissues of human origin was used. The calculations include by separate the Photoelectric effect, the Compton scattering and the Pair production, as well as the total. For to establish a comparison with the attenuation capacities, the coefficients of the water, the aluminum and the lead also were calculated. The study was complemented measuring the attenuation coefficient of hepatic tissue of bovine before gamma rays of 0.662 MeV of a source of 137 Cs. The measurement was made through of an experiment of photons transmission through samples frozen of hepatic tissue and with a Geiger-Mueller detector. (Author)

Gamma ray attenuation coefficient measurement for neutron-absorbent materials

Energy Technology Data Exchange (ETDEWEB)

Jalali, Majid [Isfahan Nuclear Science and Technology Research Institute (NSTRT), Reactor and Accelerators Research and Development School, Atomic Energy Organization (Iran, Islamic Republic of)], E-mail: m_jalali@entc.org.ir; Mohammadi, Ali [Faculty of Science, Department of Physics, University of Kashan, Km. 6, Ravand Road, Kashan (Iran, Islamic Republic of)

2008-05-15

The compounds Na{sub 2}B{sub 4}O{sub 7}, H{sub 3}BO{sub 3}, CdCl{sub 2} and NaCl and their solutions attenuate gamma rays in addition to neutron absorption. These compounds are widely used in the shielding of neutron sources, reactor control and neutron converters. Mass attenuation coefficients of gamma related to the four compounds aforementioned, in energies 662, 778.9, 867.38, 964.1, 1085.9, 1173, 1212.9, 1299.1,1332 and 1408 keV, have been determined by the {gamma} rays transmission method in a good geometry setup; also, these coefficients were calculated by MCNP code. A comparison between experiments, simulations and Xcom code has shown that the study has potential application for determining the attenuation coefficient of various compound materials. Experiment and computation show that H{sub 3}BO{sub 3} with the lowest average Z has the highest gamma ray attenuation coefficient among the aforementioned compounds.

Minimal residual cone-beam reconstruction with attenuation correction in SPECT

International Nuclear Information System (INIS)

La, Valerie; Grangeat, Pierre

1998-01-01

This paper presents an iterative method based on the minimal residual algorithm for tomographic attenuation compensated reconstruction from attenuated cone-beam projections given the attenuation distribution. Unlike conjugate-gradient based reconstruction techniques, the proposed minimal residual based algorithm solves directly a quasisymmetric linear system, which is a preconditioned system. Thus it avoids the use of normal equations, which improves the convergence rate. Two main contributions are introduced. First, a regularization method is derived for quasisymmetric problems, based on a Tikhonov-Phillips regularization applied to the factorization of the symmetric part of the system matrix. This regularization is made spatially adaptive to avoid smoothing the region of interest. Second, our existing reconstruction algorithm for attenuation correction in parallel-beam geometry is extended to cone-beam geometry. A circular orbit is considered. Two preconditioning operators are proposed: the first one is Grangeat's inversion formula and the second one is Feldkamp's inversion formula. Experimental results obtained on simulated data are presented and the shadow zone effect on attenuated data is illustrated. (author)

Segmented attenuation correction using artificial neural networks in positron tomography

International Nuclear Information System (INIS)

Yu, S.K.; Nahmias, C.

1996-01-01

The measured attenuation correction technique is widely used in cardiac positron tomographic studies. However, the success of this technique is limited because of insufficient counting statistics achievable in practical transmission scan times, and of the scattered radiation in transmission measurement which leads to an underestimation of the attenuation coefficients. In this work, a segmented attenuation correction technique has been developed that uses artificial neural networks. The technique has been validated in phantoms and verified in human studies. The results indicate that attenuation coefficients measured in the segmented transmission image are accurate and reproducible. Activity concentrations measured in the reconstructed emission image can also be recovered accurately using this new technique. The accuracy of the technique is subject independent and insensitive to scatter contamination in the transmission data. This technique has the potential of reducing the transmission scan time, and satisfactory results are obtained if the transmission data contain about 400 000 true counts per plane. It can predict accurately the value of any attenuation coefficient in the range from air to water in a transmission image with or without scatter correction. (author)

Intercomparison of attenuation correction algorithms for single-polarized X-band radars

Science.gov (United States)

Lengfeld, K.; Berenguer, M.; Sempere Torres, D.

2018-03-01

Attenuation due to liquid water is one of the largest uncertainties in radar observations. The effects of attenuation are generally inversely proportional to the wavelength, i.e. observations from X-band radars are more affected by attenuation than those from C- or S-band systems. On the other hand, X-band radars can measure precipitation fields in higher temporal and spatial resolution and are more mobile and easier to install due to smaller antennas. A first algorithm for attenuation correction in single-polarized systems was proposed by Hitschfeld and Bordan (1954) (HB), but it gets unstable in case of small errors (e.g. in the radar calibration) and strong attenuation. Therefore, methods have been developed that restrict attenuation correction to keep the algorithm stable, using e.g. surface echoes (for space-borne radars) and mountain returns (for ground radars) as a final value (FV), or adjustment of the radar constant (C) or the coefficient α. In the absence of mountain returns, measurements from C- or S-band radars can be used to constrain the correction. All these methods are based on the statistical relation between reflectivity and specific attenuation. Another way to correct for attenuation in X-band radar observations is to use additional information from less attenuated radar systems, e.g. the ratio between X-band and C- or S-band radar measurements. Lengfeld et al. (2016) proposed such a method based isotonic regression of the ratio between X- and C-band radar observations along the radar beam. This study presents a comparison of the original HB algorithm and three algorithms based on the statistical relation between reflectivity and specific attenuation as well as two methods implementing additional information of C-band radar measurements. Their performance in two precipitation events (one mainly convective and the other one stratiform) shows that a restriction of the HB is necessary to avoid instabilities. A comparison with vertically pointing

Radiation induced time dependent attenuation in a fiber

International Nuclear Information System (INIS)

Kelly, R.E.; Lyons, P.B.; Looney, L.D.

1985-01-01

Characteristics describing the time dependent attenuation coefficient of an optical fiber during and following a very short and intense radiation pulse are analyzed. This problem is important for transmission applications when the fiber is subjected to gamma, electron, or neutron beams. Besides time, the attenuation coefficient is a function of temperature, dose rate, dose, nature of the radiation (n, e, γ), fiber composition and purity, pre-existing solid state defects, and wavelength of the transmitted signal. The peak attenuation for a given fiber is mainly determined by the dose rate and pulse length, but temperature and strain (or athermal) annealing also contribute to a partial recovery during the pulse duration. The peak attenuation per unit dose appears to be smaller at high doses, perhaps caused by particle track overlap, which produces a saturation effect. After pulse termination, the attenuation coefficient tends to recover towards its pre-radiation value at different rates, depending upon the factors mentioned above. In particular, ionized electrons relax back to the positive lattice ions at a rate which depends upon initial separation distance and temperature. The initial separation distance is a function of beam energy. Some electrons will encounter a trap in the lattice and may recombine by quantum mechanical tunneling or be removed by photons (hence, absorption). Besides ionization, radiation may induce lattice displacements which in turn produce additional absorption centers. The displacement contribution has a different time constant than that associated with ionization. These topics, as they influence fiber characteristics, are discussed, along with supporting experimental data

Bulk sample self-attenuation correction by transmission measurement

International Nuclear Information System (INIS)

Parker, J.L.; Reilly, T.D.

1976-01-01

Various methods used in either finding or avoiding the attenuation correction in the passive γ-ray assay of bulk samples are reviewed. Detailed consideration is given to the transmission method, which involves experimental determination of the sample linear attenuation coefficient by measuring the transmission through the sample of a beam of gamma rays from an external source. The method was applied to box- and cylindrically-shaped samples

Neuroprotective potential of quercetin in combination with piperine against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity

Directory of Open Access Journals (Sweden)

Shamsher Singh

2017-01-01

Full Text Available 1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP is a neurotoxin that selectively damages dopaminergic neurons in the substantia nigra pars compacta and induces Parkinson's like symptoms in rodents. Quercetin (QC is a natural polyphenolic bioflavonoid with potent antioxidant and anti-inflammatory properties but lacks of clinical attraction due to low oral bioavailability. Piperine is a well established bioavailability enhancer used pre-clinically to improve the bioavailability of antioxidants (e.g., Quercetin. Therefore, the present study was designed to evaluate the neuroprotective potential of QC together with piperine against MPTP-induced neurotoxicity in rats. MPTP (100 μg/μL/rat, bilaterally was injected intranigrally on days 1, 4 and 7 using a digital stereotaxic apparatus. QC (25 and 50 mg/kg, intragastrically and QC (25 mg/kg, intragastrically in combination with piperine (2.5 mg/kg, intragastrically were administered daily for 14 days starting from day 8 after the 3rd injection of MPTP. On day 22, animals were sacrificed and the striatum was isolated for oxidative stress parameter (thiobarbituric acid reactive substances, nitrite and glutathione, neuroinflammatory cytokine (interleukin-1β, interleukin-6, and tumor necrosis factor-α and neurotransmitter (dopamine, norepinephrine, serotonin, gamma-aminobutyric acid, glutamate, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid evaluations. Bilateral infusion of MPTP into substantia nigra pars compacta led to significant motor deficits as evidenced by impairments in locomotor activity and rotarod performance in open field test and grip strength and narrow beam walk performance. Both QC (25 and 50 mg/kg and QC (25 mg/kg in combination with piperine (2.5 mg/kg, in particular the combination therapy, significantly improved MPTP-induced behavioral abnormalities in rats, reversed the abnormal alterations of neurotransmitters in the striatum, and alleviated

An acoustic eikonal equation for attenuating transversely isotropic media with a vertical symmetry axis

KAUST Repository

Hao, Qi

2016-11-21

Seismic-wave attenuation is an important component of describing wave propagation. Certain regions, such as gas clouds inside the earth, exert highly localized attenuation. In fact, the anisotropic nature of the earth induces anisotropic attenuation because the quasi P-wave dispersion effect should be profound along the symmetry direction. We have developed a 2D acoustic eikonal equation governing the complex-valued traveltime of quasi P-waves in attenuating, transversely isotropic media with a vertical-symmetry axis (VTI). This equation is derived under the assumption that the complex-valued traveltime of quasi P-waves in attenuating VTI media are independent of the S-wave velocity parameter υS0 in Thomsen\\'s notation and the S-wave attenuation coefficient AS0 in Zhu and Tsvankin\\'s notation. We combine perturbation theory and Shanks transform to develop practical approximations to the acoustic attenuating eikonal equation, capable of admitting an analytical description of the attenuation in homogeneous media. For a horizontal-attenuating VTI layer, we also derive the nonhyperbolic approximations for the real and imaginary parts of the complex-valued reflection traveltime. These equations reveal that (1) the quasi SV-wave velocity and the corresponding quasi SV-wave attenuation coefficient given as part of Thomsen-type notation barely affect the ray velocity and ray attenuation of quasi P-waves in attenuating VTI media; (2) combining the perturbation method and Shanks transform provides an accurate analytic eikonal solution for homogeneous attenuating VTI media; (3) for a horizontal attenuating VTI layer with weak attenuation, the real part of the complex-valued reflection traveltime may still be described by the existing nonhyperbolic approximations developed for nonattenuating VTI media, and the imaginary part of the complex-valued reflection traveltime still has the shape of nonhyperbolic curves. In addition, we have evaluated the possible extension of the

ADVANCING THE SCIENCE OF NATURAL AND ENHANCED ATTENUATION FOR CHLORINATED SOLVENTS

Energy Technology Data Exchange (ETDEWEB)

Looney, B; TOM O. EARLY, T; TYLER GILMORE, T; FRANCIS H. CHAPELLE, F; NORMAN H. CUTSHALL, N; JEFF ROSS, J; MARK ANKENY, M; Michael Heitkamp, M; DAVID MAJOR, D; CHARLES J. NEWELL, C; W. JODY WAUGH, W; GARY WEIN, G; Karen Vangelas, K; Karen-M Adams, K; CLAIRE H. SINK, C

2006-12-27

This report summarizes the results of a three-year program that addressed key scientific and technical aspects related to natural and enhanced attenuation of chlorinated organics. The results from this coordinated three-year program support a variety of technical and regulatory advancements. Scientists, regulators, engineers, end-users and stakeholders participated in the program, which was supported by the U.S. Department of Energy (DOE) and the Interstate Technology and Regulatory Council (ITRC). The overarching objective of the effort was to examine environmental remedies that are based on natural processes--remedies such as Monitored Natural Attenuation (MNA) or Enhanced Attenuation (EA). A key result of the recent effort was the general affirmation of the approaches and guidance in the original U.S. Environmental Protection Agency (EPA) chlorinated solvent MNA protocols and directives from 1998 and 1999, respectively. The research program did identify several specific opportunities for advances based on: (1) mass balance as the central framework for attenuation based remedies, (2) scientific advancements and achievements during the past ten years, (3) regulatory and policy development and real-world experience using MNA, and (4) exploration of various ideas for integrating attenuation remedies into a systematic set of ''combined remedies'' for contaminated sites. These opportunities are summarized herein and are addressed in more detail in referenced project documents and journal articles, as well as in the technical and regulatory documents being developed within the ITRC. Natural attenuation processes occur in all soil and groundwater systems and act, to varying degrees, on all contaminants. Thus, a decision to rely on natural attenuation processes as part of a site-remediation strategy does not depend on the occurrence of natural attenuation, but on its effectiveness in meeting site-specific remediation goals. Meeting these goals

Developement of a Light Attenuator Based on Glassy Reflections ...

African Journals Online (AJOL)

The light intensity control of a luminous source is a very important operation in many optical applications. Several types of light attenuator exploiting different optical phenomena like diffraction, absorption, and reflection exist and they differ principally in the maximum attenuation rate, the control range, the sensitivity and the ...

Experiment evaluation of impact attenuator for a racing car under static load

Science.gov (United States)

Imanullah, Fahmi; Ubaidillah, Prasojo, Arfi Singgih; Wirawan, Adhe Aji

2018-02-01

The automotive world is a world where one of the factors that must be considered carefully is the safety aspect. In the formula student car one of the safety factor in the form of impact attenuator. Impact attenuator is used as anchoring when a collision occurs in front of the vehicle. In the rule of formula society of automotive engineer (FSAE) student, impact attenuator is required to absorb the energy must meet or exceed 7350 Joules with a slowdown in speed not exceeding 20 g average and peak of 40 g. The student formula participants are challenged to pass the boundaries so that in designing and making the impact attenuator must pay attention to the strength and use of the minimum material so that it can minimize the expenditure. In this work, an impact attenuator was fabricated and tested using static compression. The primary goal was evaluating the actual capability of the impact attenuator for impact energy absorption. The prototype was made of aluminum alloy in a prismatic shape, and the inside wall was filled with rooftop plastic slices and polyurethane hard foam. The compression test has successfully carried out, and the load versus displacement data could be used in calculating energy absorption capability. The result of the absorbent energy of the selected impact attenuator material. Impact attenuator full polyurethane absorbed energy reach 6380 Joule. For impact attenuator with aluminum polyurethane with a slashed rooftop material as section absorbed energy reach 6600 Joule. Impact attenuator with Aluminum Polyurethane with aluminum orange peel partitions absorbed energy reach 8800 Joule. From standard student formula, energy absorbed in this event must meet or exceed 7350 Joules that meet aluminum polyurethane with aluminum orange peel partitions with the ability to absorb 8800 Joule.

The Study of Rain Specific Attenuation for the Prediction of Satellite Propagation in Malaysia

Science.gov (United States)

Mandeep, J. S.; Ng, Y. Y.; Abdullah, H.; Abdullah, M.

2010-06-01

Specific attenuation is the fundamental quantity in the calculation of rain attenuation for terrestrial path and slant paths representing as rain attenuation per unit distance (dB/km). Specific attenuation is an important element in developing the predicted rain attenuation model. This paper deals with the empirical determination of the power law coefficients which allow calculating the specific attenuation in dB/km from the knowledge of the rain rate in mm/h. The main purpose of the paper is to obtain the coefficients of k and α of power law relationship between specific attenuation. Three years (from 1st January 2006 until 31st December 2008) rain gauge and beacon data taken from USM, Nibong Tebal have been used to do the empirical procedure analysis of rain specific attenuation. The data presented are semi-empirical in nature. A year-to-year variation of the coefficients has been indicated and the empirical measured data was compared with ITU-R provided regression coefficient. The result indicated that the USM empirical measured data was significantly vary from ITU-R predicted value. Hence, ITU-R recommendation for regression coefficients of rain specific attenuation is not suitable for predicting rain attenuation at Malaysia.

Validity of the CT to attenuation coefficient map conversion methods

International Nuclear Information System (INIS)

Faghihi, R.; Ahangari Shahdehi, R.; Fazilat Moadeli, M.

2004-01-01

The most important commercialized methods of attenuation correction in SPECT are based on attenuation coefficient map from a transmission imaging method. The transmission imaging system can be the linear source of radioelement or a X-ray CT system. The image of transmission imaging system is not useful unless to replacement of the attenuation coefficient or CT number with the attenuation coefficient in SPECT energy. In this paper we essay to evaluate the validity and estimate the error of the most used method of this transformation. The final result shows that the methods which use a linear or multi-linear curve accept a error in their estimation. The value of mA is not important but the patient thickness is very important and it can introduce a error more than 10 percent in the final result

Live attenuated S. Typhimurium vaccine with improved safety in immuno-compromised mice.

Directory of Open Access Journals (Sweden)

Balamurugan Periaswamy

Full Text Available Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV. Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb(-/-nos2(-/- animals lacking NADPH oxidase and inducible NO synthase. In cybb(-/-nos2(-/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093, was >1000-fold attenuated in cybb(-/-nos2(-/- mice and ≈100 fold attenuated in tnfr1(-/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety.

Macroseismic intensity attenuation in Iran

Science.gov (United States)

Yaghmaei-Sabegh, Saman

2018-01-01

Macroseismic intensity data plays an important role in the process of seismic hazard analysis as well in developing of reliable earthquake loss models. This paper presents a physical-based model to predict macroseismic intensity attenuation based on 560 intensity data obtained in Iran in the time period 1975-2013. The geometric spreading and energy absorption of seismic waves have been considered in the proposed model. The proposed easy to implement relation describes the intensity simply as a function of moment magnitude, source to site distance and focal depth. The prediction capability of the proposed model is assessed by means of residuals analysis. Prediction results have been compared with those of other intensity prediction models for Italy, Turkey, Iran and central Asia. The results indicate the higher attenuation rate for the study area in distances less than 70km.

Symphony orchestra musicians′ use of hearing protection and attenuation of custom-made hearing protectors as measured with two different real-ear attenuation at threshold methods

Directory of Open Access Journals (Sweden)

K H Huttunen

2011-01-01

Full Text Available Despite a high level of sound exposure and a fairly large selection of earplugs available, musicians have often been reported to use personal hearing protectors only seldom. For better hearing conservation, it is important to identify and eliminate the causes for the low motivation to use hearing protection. We explored the usage rate of custom-molded musician′s earplugs (ER-15 among 15 symphony orchestra musicians with a questionnaire, and measured the attenuation properties of their earplugs with a Real-Ear Attenuation at Threshold (REAT procedure in a sound field. Earplug use was found to be low, and the musicians reported that earplugs hampered listening to their own and their colleagues′ playing; earplugs affected either timbre or dynamics, or both. Additionally, several reasons related to discomfort of use were itemized, but the musicians who consistently used their earplugs did so in spite of problems with use. The REAT values obtained in sound field were relatively close to the manufacturer′s nominal specifications, being 13.7 dB, on average. In the frequency range studied (0.125-8 kHz, individual variation in REAT was, however, up to 15 dB across the measured frequencies. Fluctuation in attenuation might be related to low use of hearing protectors, and REAT measured at fixed center frequencies may be too robust a method to uncover it. We therefore tested 10 additional subjects to find out whether a sweeping signal used in Bιkιsy audiometry would bring more detailed information on earplug attenuation. Mean attenuation was found to be somewhat closer to the nominal attenuation of the ER-9 and ER-15 earplugs up to about 1 kHz, whereas REAT measurements in sound field revealed more even attenuation at frequencies between 1 and 6 kHz. No significant association was found between earplug attenuation properties and earplug use. It was concluded that support and determination to get accustomed to hearing protector use are important

Brain structural changes in cynomolgus monkeys administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A longitudinal voxel-based morphometry and diffusion tensor imaging study.

Directory of Open Access Journals (Sweden)

Hyeonseok S Jeong

Full Text Available In animal models of Parkinson's disease (PD, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP is one of the most widely used agents that damages the nigrostriatal dopaminergic pathway. However, brain structural changes in response to MPTP remain unclear. This study aimed to investigate in vivo longitudinal changes in gray matter (GM volume and white matter (WM microstructure in primate models administered with MPTP. In six cynomolgus monkeys, high-resolution magnetic resonance imaging (MRI and diffusion tensor imaging (DTI scans were acquired 7 times over 32 weeks, and assessments of motor symptoms were conducted over 15 months, before and after the MPTP injection. Changes in GM volume and WM microstructure were estimated on a voxel-by-voxel basis. Mixed-effects regression models were used to examine the trajectories of these structural changes. GM volume initially increased after the MPTP injection and gradually decreased in the striatum, midbrain, and other dopaminergic areas. The cerebellar volume temporarily decreased and returned to its baseline level. The rate of midbrain volume increase was positively correlated with the increase rate of motor symptom severity (Spearman rho = 0.93, p = 0.008. Mean, axial, and radial diffusivity in the striatum and frontal areas demonstrated initial increases and subsequent decreases. The current multi-modal imaging study of MPTP-administered monkeys revealed widespread and dynamic structural changes not only in the nigrostriatal pathway but also in other cortical, subcortical, and cerebellar areas. Our findings may suggest the need to further investigate the roles of inflammatory reactions and glial activation as potential underlying mechanisms of these structural changes.

Indirect application of near infrared light induces neuro-protection in a mouse model of parkinsonism - an abscopal neuro-protective effective evaluation

International Nuclear Information System (INIS)

Johnstone, D.M.; Spana, S.; Purushothuman, S.; Stone, J.; Mitrofanis, J.; Johnstone, D.M.; Spana, S.; Purushothuman, S.; Stone, J.; El Massri, N.; Mitrofanis, J.; Moro, C.; Torres, N.; Chabrol, C.; De Jaeger, X.; Reinhart, F.; Benabid, A.L.; Wang, X.S.

2014-01-01

We have previously shown near infrared light (NIr), directed transcranially, mitigates the loss of dopaminergic cells in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mice, a model of parkinsonism. These findings complement others suggesting NIr treatment protects against damage from various insults. However one puzzling feature of NIr treatment is that unilateral exposure can lead to a bilateral healing response, suggesting NIr may have 'indirect' protective effects. We investigated whether remote NIr treatment is neuro-protective by administering different MPTP doses (50-, 75-, 100-mg/kg) to mice and treating with 670-nm light directed specifically at either the head or body. Our results show that, despite no direct irradiation of the damaged tissue, remote NIr treatment produces a significant rescue of tyrosine hydroxylase-positive cells in the substantia nigra pars compacta at the milder MPTP dose of 50-mg/kg (30% increase vs sham-treated MPTP mice, p≤ 0.05). However this protection did not appear as robust as that achieved by direct irradiation of the head (50% increase vs sham-treated MPTP mice, p ≤0.001). There was no quantifiable protective effect of NIr at higher MPTP doses, irrespective of the delivery mode. Astrocyte and microglia cell numbers in substantia nigra pars compacta were not influenced by either mode of NIr treatment. In summary, the findings suggest that treatment of a remote tissue with NIr is sufficient to induce protection of the brain, reminiscent of the 'abscopal effect' sometimes observed in radiation treatment of metastatic cancer. This discovery has implications for the clinical translation of light-based therapies, providing an improved mode of delivery over trans-cranial irradiation. (authors)

Whole-body PET/MRI: The effect of bone attenuation during MR-based attenuation correction in oncology imaging

Energy Technology Data Exchange (ETDEWEB)

Aznar, M.C., E-mail: marianne.aznar@regionh.dk [Department of Oncology, Section of Radiotherapy 3994, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen (Denmark); Sersar, R., E-mail: rachidadk@hotmail.com [DTU Informatics, Technical University of Denmark, Kongens Lyngby (Denmark); Saabye, J., E-mail: julie_saa@hotmail.com [DTU Informatics, Technical University of Denmark, Kongens Lyngby (Denmark); Ladefoged, C.N., E-mail: claesnl@gmail.com [Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen (Denmark); Andersen, F.L., E-mail: Flemming.Andersen@regionh.dk [Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen (Denmark); Rasmussen, J.H., E-mail: jacobrasmu@gmail.com [Department of Oncology, Section of Radiotherapy 3994, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen (Denmark); Löfgren, J., E-mail: Johan.Loefgren@regionh.dk [Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen (Denmark); Beyer, T., E-mail: thomas.beyer@meduniwien.ac.at [Centre for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna (Austria)

2014-07-15

Purpose: In combined PET/MRI standard PET attenuation correction (AC) is based on tissue segmentation following dedicated MR sequencing and, typically, bone tissue is not represented. We evaluate PET quantification in whole-body (WB)-PET/MRI following MR-AC without considering bone attenuation and then investigate different strategies to account for bone tissue in clinical PET/MR imaging. To this purpose, bone tissue representation was extracted from separate CT images, and different bone representations were simulated from hypothetically derived MR-based bone classifications. Methods: Twenty oncology patients referred for a PET/CT were injected with either [18F]-FDG or [18F]-NaF and imaged on PET/CT (Biograph TruePoint/mCT, Siemens) and PET/MRI (mMR, Siemens) following a standard single-injection, dual-imaging clinical WB-protocol. Routine MR-AC was based on in-/opposed-phase MR imaging (orgMR-AC). PET(/MRI) images were reconstructed (AW-OSEM, 3 iterations, 21 subsets, 4 mm Gaussian) following routine MR-AC and MR-AC based on four modified attenuation maps. These modified attenuation maps were created for each patient by non-linear co-registration of the CT images to the orgMR-AC images, and adding CT bone mask values representing cortical bone: 1200 HU (cortCT), spongiosa bone: 350 HU (spongCT), average CT value (meanCT) and original CT values (orgCT). Relative difference images of the PET following AC using the modified attenuation maps were compared. SUVmean was calculated in anatomical reference regions and for PET-positive lesions. Results: The relative differences in SUVmean across patients following orgMR-AC and orgCT in soft tissue lesions and in bone lesions were similar (range: 0.0% to −22.5%), with an average underestimation of SUVmean of 7.2% and 10.0%, respectively when using orgMR-AC. In bone lesions, spongCT values were closest to orgCT (median bias of 1.3%, range: –9.0% to 13.5%) while the overestimation of SUVmean with respect to orgCT was

Pentoxifylline Attenuates Cardiac Remodeling Induced by Tobacco Smoke Exposure

Energy Technology Data Exchange (ETDEWEB)

Minicucci, Marcos; Oliveira, Fernando; Santos, Priscila; Polegato, Bertha; Roscani, Meliza; Fernandes, Ana Angelica; Lustosa, Beatriz; Paiva, Sergio; Zornoff, Leonardo; Azevedo, Paula, E-mail: paulasa@fmb.unesp.br [Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, São Paulo, SP (Brazil)

2016-05-15

Tobacco smoke exposure is an important risk factor for cardiac remodeling. Under this condition, inflammation, oxidative stress, energy metabolism abnormalities, apoptosis, and hypertrophy are present. Pentoxifylline has anti‑inflammatory, anti-apoptotic, anti-thrombotic and anti-proliferative properties. The present study tested the hypothesis that pentoxifylline would attenuate cardiac remodeling induced by smoking. Wistar rats were distributed in four groups: Control (C), Pentoxifylline (PX), Tobacco Smoke (TS), and PX-TS. After two months, echocardiography, invasive blood pressure measurement, biochemical, and histological studies were performed. The groups were compared by two-way ANOVA with a significance level of 5%. TS increased left atrium diameter and area, which was attenuated by PX. In the isolated heart study, TS lowered the positive derivate (+dp/dt), and this was attenuated by PX. The antioxidants enzyme superoxide dismutase and glutathione peroxidase were decreased in the TS group; PX recovered these activities. TS increased lactate dehydrogenase (LDH) and decreased 3-hydroxyacyl Coenzyme A dehydrogenases (OH-DHA) and citrate synthase (CS). PX attenuated LDH, 3-OH-DHA and CS alterations in TS-PX group. TS increased IL-10, ICAM-1, and caspase-3. PX did not influence these variables. TS induced cardiac remodeling, associated with increased inflammation, oxidative stress, apoptosis, and changed energy metabolism. PX attenuated cardiac remodeling by reducing oxidative stress and improving cardiac bioenergetics, but did not act upon cardiac cytokines and apoptosis.

Broad beam X-rays attenuation in silicum glass

International Nuclear Information System (INIS)

Risticj, Dj.; Vukovicj, S.; Markovicj, P.

1987-01-01

Using broad beam geometry the attenuation for domestic silicum glass have been studied for constant X-ray potentials from 50 to 150 kV. The density of the silicium glass was 2,5x10 3 kg/m 3 . From the attenuation curves the half value layers were obtained. The use of this glass as the biological shield is pointed out. (author). 2 refs.; 2 tabs.; 2 figs

Statistical problems with weather-radar images, II: Attenuation detection

International Nuclear Information System (INIS)

Fernandez-Duran, Juan-Jose; Upton, Graham

2003-01-01

A procedure based on the combination of a Bayesian changepoint model and ordinary least squares is used to identify and quantify regions where a radar signal has been attenuated (i.e.diminished) as a consequence of intervening weather. A graphical polar display is introduced that illustrates the location and importance of the attenuation

MicroRNA-Based Attenuation of Influenza Virus across Susceptible Hosts.

Science.gov (United States)

Waring, Barbara M; Sjaastad, Louisa E; Fiege, Jessica K; Fay, Elizabeth J; Reyes, Ismarc; Moriarity, Branden; Langlois, Ryan A

2018-01-15

Influenza A virus drives significant morbidity and mortality in humans and livestock. Annual circulation of the virus in livestock and waterfowl contributes to severe economic disruption and increases the risk of zoonotic transmission of novel strains into the human population, where there is no preexisting immunity. Seasonal vaccinations in humans help prevent infection and can reduce symptoms when infection does occur. However, current vaccination regimens available for livestock are limited in part due to safety concerns regarding reassortment/recombination with circulating strains. Therefore, inactivated vaccines are used instead of the more immunostimulatory live attenuated vaccines. MicroRNAs (miRNAs) have been used previously to generate attenuated influenza A viruses for use as a vaccine. Here, we systematically targeted individual influenza gene mRNAs using the same miRNA to determine the segment(s) that yields maximal attenuation potential. This analysis demonstrated that targeting of NP mRNA most efficiently ablates replication. We further increased the plasticity of miRNA-mediated attenuation of influenza A virus by exploiting a miRNA, miR-21, that is ubiquitously expressed across influenza-susceptible hosts. In order to construct this targeted virus, we used CRISPR/Cas9 to eliminate the universally expressed miR-21 from MDCK cells. miR-21-targeted viruses were attenuated in human, mouse, canine, and avian cells and drove protective immunity in mice. This strategy has the potential to enhance the safety of live attenuated vaccines in humans and zoonotic reservoirs. IMPORTANCE Influenza A virus circulates annually in both avian and human populations, causing significant morbidity, mortality, and economic burden. High incidence of zoonotic infections greatly increases the potential for transmission to humans, where no preexisting immunity or vaccine exists. There is a critical need for new vaccine strategies to combat emerging influenza outbreaks. Micro

Using Tectonic Tremor to Constrain Seismic-wave Attenuation in Cascadia

Science.gov (United States)

Littel, G.; Thomas, A.; Baltay, A.

2017-12-01

In addition to fast, seismic slip, many subduction zones also host slow, largely aseismic slip, accompanied by a weak seismic signal known as tectonic tremor. Tremor is a small amplitude, low-frequency seismic signal that originates at the plate interface, down-dip of where large earthquakes typically occur. The Cascadia subduction zone has not seen a large megathrust earthquake since 1700, yet its recurrence interval of 350-500 years motivates heightened interest in understanding the seismic hazard of the region. Of great importance is to understand the degree to which waves are attenuated as they leave the plate interface and travel towards populated regions of interest. Ground motion prediction equations (GMPEs) relate ground motion to a number of parameters, including earthquake magnitude, depth, style of faulting, and anelastic attenuation, and are typically determined empirically from earthquake ground motion recordings. In Cascadia, however, earthquakes of the moderate size typically used to constrain GMPEs occur relatively infrequently compared to tectonic tremor events, which, in contrast, occur periodically approximately every 10-19 months. Studies have shown that the abundant tectonic tremor in Cascadia, despite its small amplitudes, can be used to constrain seismic wave attenuation in GMPEs. Here we quantify seismic wave attenuation and determine its spatial variations in Cascadia by performing an inversion using tremor ground motion amplitudes, taken as peak ground acceleration (PGA) and peak ground velocity (PGV) from 1 min window waveforms of each individual tremor event. We estimate the anelastic attenuation parameter for varying regional sections along the Cascadia margin. Changes in seismic-wave attenuation along the Cascadia Subduction Zone could result in significantly different ground motions in the event of a very large earthquake, hence quantifying attenuation may help to better estimate the severity of shaking in densely populated

Determination of Dimensionless Attenuation Coefficient in Shaped Resonators

Science.gov (United States)

Daniels, C.; Steinetz, B.; Finkbeiner, J.; Raman, G.; Li, X.

2003-01-01

The value of dimensionless attenuation coefficient is an important factor when numerically predicting high-amplitude acoustic waves in shaped resonators. Both the magnitude of the pressure waveform and the quality factor rely heavily on this dimensionless parameter. Previous authors have stated the values used, but have not completely explained their methods. This work fully describes the methodology used to determine this important parameter. Over a range of frequencies encompassing the fundamental resonance, the pressure waves were experimentally measured at each end of the shaped resonators. At the corresponding dimensionless acceleration, the numerical code modeled the acoustic waveforms generated in the resonator using various dimensionless attenuation coefficients. The dimensionless attenuation coefficient that most closely matched the pressure amplitudes and quality factors of the experimental and numerical results was determined to be the value to be used in subsequent studies.

Utilization of ilmenite/epoxy composite for neutrons and gamma rays attenuation

Energy Technology Data Exchange (ETDEWEB)

El-Sayed Abdo, A. E-mail: attiaabdo11@hotmail.com; El-Sarraf, M.A.; Gaber, F.A

2003-01-01

This work deals with the study of ilmenite/epoxy composite as an injecting mortar for cracks developed in biological concrete shields, as well as, neutrons and gamma rays attenuation. Effects of the particle size on the mechanical strengths have been studied for epoxy resin filled with crushed ilmenite with different maximum particle sizes ranging from 32 to 500 {mu}m. Thermal neutrons and gamma rays attenuation in ilmenite/epoxy composites with 75 and 80 wt.% of ilmenite concentration have been investigated. The total mass attenuation coefficients {mu}/{rho} (cm{sup 2} g{sup -1}) of gamma ray for five ilmenite/epoxy composites have been calculated using the XCOM program (version 3.1) at energies from 10 keV to 100 MeV. Also, the total mass attenuation coefficients ({mu}/{rho}) have estimated based on the measured total linear attenuation coefficients ({mu}) and compared with the calculated results where, a reasonable agreement was found.

Viability of natural attenuation in a petroleum-contaminated shallow sandy aquifer

International Nuclear Information System (INIS)

Jin Yong Lee; Kang Kun Lee

2003-01-01

This study focused on evaluating and quantifying the potential of natural attenuation of groundwater at a petroleum-contaminated site in an industrial area of a satellite city of Seoul, Korea. Groundwater at the study site was contaminated with toluene, ethylbenzene and xylene (TEX). Eight rounds of groundwater sampling and subsequent chemical analyses were performed over a period of 3 years. The groundwater quality data suggest that TEX concentrations at this site have been decreasing with time and that the TEX plume is at a quasi-steady state. Trend analysis, changes in mass flux and plume area also confirmed that the TEX plume has reached a quasi-steady state. The proportion of the total attenuation attributable to biodegradation has decreased over the monitoring period while contribution of other attenuation processes, such as dilution or dispersion, has increased. Based on the calculated attenuation rates, it would take more than 20 years to clean up the site by natural attenuation alone. (author)

Characteristics of liver tissue for attenuate the gamma radiation

International Nuclear Information System (INIS)

Arcos P, A.; Rodriguez N, S.; Pinedo S, A.; Amador V, P.; Chacon R, A.; Vega C, H.R.

2005-01-01

It was determined the lineal attenuation coefficient of hepatic tissue before gamma radiation of a source of 137 Cs. When exposing organic material before X or gamma radiation fields, part of the energy of the photons is absorbed by the material, while another part crosses it without producing any effect. The quantity of energy that is absorbed is a measure of the dose that receives the material. The three main mechanisms by means of which the gamma rays interacting with the matter are: The Photoelectric Effect, the Compton dispersion and the Even production; the sum of these three processes is translated in the attenuation coefficient of the radiation. In this work we have used hepatic tissue of bovine, as substitute of the human hepatic tissue, and we have measured the lineal attenuation coefficient for photons of 0.662 MeV. Through a series of calculations we have determined the lineal attenuation coefficient for photons from 10 -3 to 10 -5 MeV and the measured coefficient was compared with the one calculated. (Author)

The antioxidative effect of electro-acupuncture in a mouse model of Parkinson's disease.

Directory of Open Access Journals (Sweden)

Haomin Wang

Full Text Available Accumulating evidence indicates that oxidative stress plays a critical role in Parkinson's disease (PD. Our previous work has shown that 100 Hz electro-acupuncture (EA stimulation at ZUSANLI (ST36 and SANYINJIAO (SP6 protects neurons in the substantia nigra pars compacta from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP toxicity in male C57BL/6 mice, a model of PD. In the present study we administered 100 Hz EA stimulation at the two acupoints to MPTP-lesioned mice for 12 sessions starting from the day prior to the first MPTP injection. We found that in the striatum of MPTP treated mice 100 Hz EA stimulation effectively inhibited the production of hydrogen peroxide and malonaldehyde, and increased glutathione concentration and total superoxide dismutase activity through biochemical methods. However, it decreased glutathione peroxidase activity via biochemical analysis and did not affect the level of 1-methyl-4-phenylpyridinium in the striatum revealed by high performance liquid chromatography with ultraviolet detection. These data suggest that 100 Hz EA stimulation at ST36 and SP6 has antioxidative effects in the MPTP model of PD. This data, along with our previous work, indicates that 100 Hz EA stimulation at ST36 and SP6 protects the nigrostriatal system by multiple mechanisms including antioxidation and antiapoptosis, and suggests that EA stimulation is a promising therapy for treating PD.

Chlorine signal attenuation in concrete.

Science.gov (United States)

Naqvi, A A; Maslehuddin, M; Ur-Rehman, Khateeb; Al-Amoudi, O S B

2015-11-01

The intensity of prompt gamma-ray was measured at various depths from chlorine-contaminated silica fume (SF) concrete slab concrete specimens using portable neutron generator-based prompt gamma-ray setup. The intensity of 6.11MeV chloride gamma-rays was measured from the chloride contaminated slab at distance of 15.25, 20.25, 25.25, 30.25 and 35.25cm from neutron target in a SF cement concrete slab specimens. Due to attenuation of thermal neutron flux and emitted gamma-ray intensity in SF cement concrete at various depths, the measured intensity of chlorine gamma-rays decreases non-linearly with increasing depth in concrete. A good agreement was noted between the experimental results and the results of Monte Carlo simulation. This study has provided useful experimental data for evaluating the chloride contamination in the SF concrete utilizing gamma-ray attenuation method. Copyright © 2015 Elsevier Ltd. All rights reserved.

Attenuation Modified by DIG and Dust as Seen in M31

Energy Technology Data Exchange (ETDEWEB)

Tomičić, Neven; Kreckel, Kathryn; Schinnerer, Eva [Max Planck Institute for Astronomy (MPIA), Königstuhl 17, 69117 Heidelberg (Germany); Groves, Brent [School of Astronomy and Astrophysics, Australian National University, Canberra, ACT 2611 (Australia); Sandstrom, Karin [Center for Astrophysics and Space Sciences, Department of Physics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (United States); Kapala, Maria [Department of Astronomy, University of Cape Town, Republic of South Africa (South Africa); Blanc, Guillermo A. [Observatories of the Carnegie Institution for Science, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); Leroy, Adam, E-mail: tomicic@mpia-hd.mpg.de [Department of Astronomy, The Ohio State University, 140 West 18th Avenue, Columbus, OH 43210 (United States)

2017-08-01

The spatial distribution of dust in galaxies affects the global attenuation, and hence inferred properties, of galaxies. We trace the spatial distribution of dust in five approximately kiloparsec fields of M31 by comparing optical attenuation with the total dust mass distribution. We measure the attenuation from the Balmer decrement using Integral Field Spectroscopy and the dust mass from Herschel far-IR observations. Our results show that M31's dust attenuation closely follows a foreground screen model, contrary to what was previously found in other nearby galaxies. By smoothing the M31 data, we find that spatial resolution is not the cause for this difference. Based on the emission-line ratios and two simple models, we conclude that previous models of dust/gas geometry need to include a weakly or non-attenuated diffuse ionized gas (DIG) component. Due to the variation of dust and DIG scale heights with galactic radius, we conclude that different locations in galaxies will have different vertical distributions of gas and dust and therefore different measured attenuation. The difference between our result in M31 with that found in other nearby galaxies can be explained by our fields in M31 lying at larger galactic radii than the previous studies that focused on the centers of galaxies.

Seismic Full Waveform Modeling & Imaging in Attenuating Media

Science.gov (United States)

Guo, Peng

Seismic attenuation strongly affects seismic waveforms by amplitude loss and velocity dispersion. Without proper inclusion of Q parameters, errors can be introduced for seismic full waveform modeling and imaging. Three different (Carcione's, Robertsson's, and the generalized Robertsson's) isotropic viscoelastic wave equations based on the generalized standard linear solid (GSLS) are evaluated. The second-order displacement equations are derived, and used to demonstrate that, with the same stress relaxation times, these viscoelastic formulations are equivalent. By introducing separate memory variables for P and S relaxation functions, Robertsson's formulation is generalized to allow different P and S wave stress relaxation times, which improves the physical consistency of the Qp and Qs modelled in the seismograms.The three formulations have comparable computational cost. 3D seismic finite-difference forward modeling is applied to anisotropic viscoelastic media. The viscoelastic T-matrix (a dynamic effective medium theory) relates frequency-dependent anisotropic attenuation and velocity to reservoir properties in fractured HTI media, based on the meso-scale fluid flow attenuation mechanism. The seismic signatures resulting from changing viscoelastic reservoir properties are easily visible. Analysis of 3D viscoelastic seismograms suggests that anisotropic attenuation is a potential tool for reservoir characterization. To compensate the Q effects during reverse-time migration (RTM) in viscoacoustic and viscoelastic media, amplitudes need to be compensated during wave propagation; the propagation velocity of the Q-compensated wavefield needs to be the same as in the attenuating wavefield, to restore the phase information. Both amplitude and phase can be compensated when the velocity dispersion and the amplitude loss are decoupled. For wave equations based on the GSLS, because Q effects are coupled in the memory variables, Q-compensated wavefield propagates faster than

Natural attenuation of herbicides

DEFF Research Database (Denmark)

Tuxen, Nina; Højberg, Anker Lajer; Broholm, Mette Martina

2002-01-01

A field injection experiment in a sandy, aerobic aquifer showed that two phenoxy acids MCPP (mecoprop) and dichlorprop were degraded within I in downgradient of the injection wells after an apparent lag period. The plume development and microbial measurements indicated that microbial growth gover....... The observations may be important for application of natural attenuation as a remedy in field scale systems....

Natural attenuation: A feasible approach to remediation of landfill leachate plumes?

DEFF Research Database (Denmark)

Christensen, Thomas Højlund; Kjeldsen, Peter; Bjerg, Poul Løgstrup

2000-01-01

Natural attenuation has been implemented for petroleum hydrocarbons plumes and recently also for chlorinated solvent plumes, primarily in the USA, but natural attenuation has not yet gained a foothold with respect to leachate plumes. Based on the experiences gained from ten years of research on two...... Danish landfills, it is suggested that natural attenuation is a feasible approach, but much more complicated and demanding than in the case of petroleum hydrocarbons and chlorinated solvent....

The ultraviolet attenuation law in backlit spiral galaxies

International Nuclear Information System (INIS)

Keel, William C.; Manning, Anna M.; Holwerda, Benne W.; Lintott, Chris J.; Schawinski, Kevin

2014-01-01

The effective extinction law (attenuation behavior) in galaxies in the emitted ultraviolet (UV) regime is well known only for actively star-forming objects and combines effects of the grain properties, fine structure in the dust distribution, and relative distributions of stars and dust. We use Galaxy Evolution Explorer, XMM Optical Monitor, and Hubble Space Telescope (HST) data to explore the UV attenuation in the outer parts of spiral disks which are backlit by other UV-bright galaxies, starting with the candidate list of pairs provided by Galaxy Zoo participants. New optical images help to constrain the geometry and structure of the target galaxies. Our analysis incorporates galaxy symmetry, using non-overlapping regions of each galaxy to derive error estimates on the attenuation measurements. The entire sample has an attenuation law across the optical and UV that is close to the Calzetti et al. form; the UV slope for the overall sample is substantially shallower than found by Wild et al., which is a reasonable match to the more distant galaxies in our sample but not to the weighted combination including NGC 2207. The nearby, bright spiral NGC 2207 alone gives an accuracy almost equal to the rest of our sample, and its outer arms have a very low level of foreground starlight. Thus, this widespread, fairly 'gray' law can be produced from the distribution of dust alone, without a necessary contribution from differential escape of stars from dense clouds. Our results indicate that the extrapolation needed to compare attenuation between backlit galaxies at moderate redshifts from HST data, and local systems from Sloan Digital Sky Survey and similar data, is mild enough to allow the use of galaxy overlaps to trace the cosmic history of dust in galaxies. For NGC 2207, HST data in the near-UV F336W band show that the covering factor of clouds with small optical attenuation becomes a dominant factor farther into the UV, which opens the possibility that

The ultraviolet attenuation law in backlit spiral galaxies

Energy Technology Data Exchange (ETDEWEB)

Keel, William C. [Department of Physics and Astronomy, University of Alabama, Box 870324, Tuscaloosa, AL 35487 (United States); Manning, Anna M. [Stennis Space Center, MS 39522 (United States); Holwerda, Benne W. [ESA-ESTEC, Keplerlaan 1, 2201-AZ Noordwijk (Netherlands); Lintott, Chris J. [Astrophysics, Oxford University, Denys Wilkinson Building, Keble Road, Oxford OX1 3RH (United Kingdom); Schawinski, Kevin, E-mail: wkeel@ua.edu, E-mail: ammanning@bama.ua.edu, E-mail: bholwerd@rssd.esa.int, E-mail: Twitter@BenneHolwerda, E-mail: cjl@astro.ox.ac.uk, E-mail: Twitter@chrislintott, E-mail: kevin.schawinski@phys.ethz.ch, E-mail: Twitter@kevinschawinski [Institute for Astronomy, ETH Zürich, Wolfgang-Pauli-Strasse 27, CH-8093 Zurich (Switzerland)

2014-02-01

The effective extinction law (attenuation behavior) in galaxies in the emitted ultraviolet (UV) regime is well known only for actively star-forming objects and combines effects of the grain properties, fine structure in the dust distribution, and relative distributions of stars and dust. We use Galaxy Evolution Explorer, XMM Optical Monitor, and Hubble Space Telescope (HST) data to explore the UV attenuation in the outer parts of spiral disks which are backlit by other UV-bright galaxies, starting with the candidate list of pairs provided by Galaxy Zoo participants. New optical images help to constrain the geometry and structure of the target galaxies. Our analysis incorporates galaxy symmetry, using non-overlapping regions of each galaxy to derive error estimates on the attenuation measurements. The entire sample has an attenuation law across the optical and UV that is close to the Calzetti et al. form; the UV slope for the overall sample is substantially shallower than found by Wild et al., which is a reasonable match to the more distant galaxies in our sample but not to the weighted combination including NGC 2207. The nearby, bright spiral NGC 2207 alone gives an accuracy almost equal to the rest of our sample, and its outer arms have a very low level of foreground starlight. Thus, this widespread, fairly 'gray' law can be produced from the distribution of dust alone, without a necessary contribution from differential escape of stars from dense clouds. Our results indicate that the extrapolation needed to compare attenuation between backlit galaxies at moderate redshifts from HST data, and local systems from Sloan Digital Sky Survey and similar data, is mild enough to allow the use of galaxy overlaps to trace the cosmic history of dust in galaxies. For NGC 2207, HST data in the near-UV F336W band show that the covering factor of clouds with small optical attenuation becomes a dominant factor farther into the UV, which opens the possibility that

Attenuation correction method for single photon emission CT

Energy Technology Data Exchange (ETDEWEB)

Morozumi, Tatsuru; Nakajima, Masato [Keio Univ., Yokohama (Japan). Faculty of Science and Technology; Ogawa, Koichi; Yuta, Shinichi

1983-10-01

A correction method (Modified Correction Matrix method) is proposed to implement iterative correction by exactly measuring attenuation constant distribution in a test body, calculating a correction factor for every picture element, then multiply the image by these factors. Computer simulation for the comparison of the results showed that the proposed method was specifically more effective to an application to the test body, in which the rate of attenuation constant change is large, than the conventional correction matrix method. Since the actual measurement data always contain quantum noise, the noise was taken into account in the simulation. However, the correction effect was large even under the noise. For verifying its clinical effectiveness, the experiment using an acrylic phantom was also carried out. As the result, the recovery of image quality in the parts with small attenuation constant was remarkable as compared with the conventional method.

Consideration of natural attenuation. In remedation contaminated sites

Energy Technology Data Exchange (ETDEWEB)

NONE

2011-04-15

Upon the proposal submitted by ist Standing committee 5 (Contaminated Sites Committee - ALA) the Federal / State Working Group on Soil protection employed an ad hoc subcommittee dealing with considering natural attenuation in remediating contaminated sites and preparing an inter-State position paper. In the present position paper the way how to consider natural attenuation in practical remediation of contaminated sites is described. The systematic approach outlined allows an understandable decision-finding. A way is shown how the competent soil protection authorities may exercise discretion and in the framework of checking the appropriateness of measures may decide on the implementation of MNA based on a MNA concept (MNA = monitored natural attenuation). It is, however, also explained that when carrying out MNA a decision always made in an individual case is concerned which should be made in a close agreement between the obligated party and the authority.

Two media method for linear attenuation coefficient determination of irregular soil samples

International Nuclear Information System (INIS)

Vici, Carlos Henrique Georges

2004-01-01

In several situations of nuclear applications, the knowledge of gamma-ray linear attenuation coefficient for irregular samples is necessary, such as in soil physics and geology. This work presents the validation of a methodology for the determination of the linear attenuation coefficient (μ) of irregular shape samples, in such a way that it is not necessary to know the thickness of the considered sample. With this methodology irregular soil samples (undeformed field samples) from Londrina region, north of Parana were studied. It was employed the two media method for the μ determination. It consists of the μ determination through the measurement of a gamma-ray beam attenuation by the sample sequentially immersed in two different media, with known and appropriately chosen attenuation coefficients. For comparison, the theoretical value of μ was calculated by the product of the mass attenuation coefficient, obtained by the WinXcom code, and the measured value of the density sample. This software employs the chemical composition of the samples and supplies a table of the mass attenuation coefficients versus the photon energy. To verify the validity of the two media method, compared with the simple gamma ray transmission method, regular pome stone samples were used. With these results for the attenuation coefficients and their respective deviations, it was possible to compare the two methods. In this way we concluded that the two media method is a good tool for the determination of the linear attenuation coefficient of irregular materials, particularly in the study of soils samples. (author)

Attenuation of Self-Generated Tactile Sensations is Predictive, not Postdictive.

Directory of Open Access Journals (Sweden)

2006-01-01

Full Text Available When one finger touches the other, the resulting tactile sensation is perceived as weaker than the same stimulus externally imposed. This attenuation of sensation could result from a predictive process that subtracts the expected sensory consequences of the action, or from a postdictive process that alters the perception of sensations that are judged after the event to be self-generated. In this study we observe attenuation even when the fingers unexpectedly fail to make contact, supporting a predictive process. This predictive attenuation of self-generated sensation may have evolved to enhance the perception of sensations with an external cause.

Attenuation of self-generated tactile sensations is predictive, not postdictive.

Directory of Open Access Journals (Sweden)

Paul M Bays

2006-02-01

Full Text Available When one finger touches the other, the resulting tactile sensation is perceived as weaker than the same stimulus externally imposed. This attenuation of sensation could result from a predictive process that subtracts the expected sensory consequences of the action, or from a postdictive process that alters the perception of sensations that are judged after the event to be self-generated. In this study we observe attenuation even when the fingers unexpectedly fail to make contact, supporting a predictive process. This predictive attenuation of self-generated sensation may have evolved to enhance the perception of sensations with an external cause.

Quantitative SPECT brain imaging: Effects of attenuation and detector response

International Nuclear Information System (INIS)

Gilland, D.R.; Jaszczak, R.J.; Bowsher, J.E.; Turkington, T.G.; Liang, Z.; Greer, K.L.; Coleman, R.E.

1993-01-01

Two physical factors that substantially degrade quantitative accuracy in SPECT imaging of the brain are attenuation and detector response. In addition to the physical factors, random noise in the reconstructed image can greatly affect the quantitative measurement. The purpose of this work was to implement two reconstruction methods that compensate for attenuation and detector response, a 3D maximum likelihood-EM method (ML) and a filtered backprojection method (FB) with Metz filter and Chang attenuation compensation, and compare the methods in terms of quantitative accuracy and image noise. The methods were tested on simulated data of the 3D Hoffman brain phantom. The simulation incorporated attenuation and distance-dependent detector response. Bias and standard deviation of reconstructed voxel intensities were measured in the gray and white matter regions. The results with ML showed that in both the gray and white matter regions as the number of iterations increased, bias decreased and standard deviation increased. Similar results were observed with FB as the Metz filter power increased. In both regions, ML had smaller standard deviation than FB for a given bias. Reconstruction times for the ML method have been greatly reduced through efficient coding, limited source support, and by computing attenuation factors only along rays perpendicular to the detector

Wild type measles virus attenuation independent of type I IFN

Directory of Open Access Journals (Sweden)

Horvat Branka

2008-02-01

Full Text Available Abstract Background Measles virus attenuation has been historically performed by adaptation to cell culture. The current dogma is that attenuated virus strains induce more type I IFN and are more resistant to IFN-induced protection than wild type (wt. Results The adaptation of a measles virus isolate (G954-PBL by 13 passages in Vero cells induced a strong attenuation of this strain in vivo. The adapted virus (G954-V13 differs from its parental strain by only 5 amino acids (4 in P/V/C and 1 in the M gene. While a vaccine strain, Edmonston Zagreb, could replicate equally well in various primate cells, both G954 strains exhibited restriction to the specific cell type used initially for their propagation. Surprisingly, we observed that both G954 strains induced type I IFN, the wt strain inducing even more than the attenuated ones, particularly in human plasmacytoid Dendritic Cells. Type I IFN-induced protection from the infection of both G954 strains depended on the cell type analyzed, being less efficient in the cells used to grow the viral strain. Conclusion Thus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the α/β IFN system.

Numerical simulation of several impact attenuator design for a formula student car

Science.gov (United States)

Sinaga, Farlian Rizky; Ubaidillah, Kurniawan, Krishna Eka; Fadhil, Muhamad Ivan; Cahyono, Sukmaji Indro; Idris, Muhamad Hafiz

2018-02-01

In the Formula Society of Automotive Engineer (SAE), safety is a vigorous factor. One of the safety components in the Formula SAE car is the impact attenuator. The purpose of this study is to get the impact attenuator design with the best ability to absorb kinetic energy from several existing designs, through numerical approaches, for estimating conditions against dynamic impacts. Material of impact attenuator use combination of aluminum and Zirconium G350. The simulation was caried out by crashing the impact with the rigid wall, to find the deformation that occurs and the energies are absorbed. The impact attenuator design to be simulated should be optimized to meet some parameters in the SAE Formula. The result of impact attenuator simulation should be able to absorb energy of 7350 joules at move 7 m/s and deformation at bulkhead less than 25.4 mm.

PET imaging using parkinsonian primate model

International Nuclear Information System (INIS)

Nagai, Yuji

2004-01-01

Many animal models have been for studying neutrodegenerative diseases in humans. Among them, Parkinson's disease (PD) model in primates treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is expected to be valid and useful in the field of regenerative medicine. MPTP-treated monkeys demonstrate parkinsonian syndrome, such as tremor, dyskinesia, rigidity, immobility, caused by the degeneration of dopamine neurons at the nigrostriatal pathway. In this model, investigation of cognitive impairment that is one of the important aspects of PD could be possible. We evaluated the degeneration process of nigrostriatal dopamine neurons with positron emission tomography (PET) using unanesthetized MPTP-treated two cynomolgus monkeys (Macaca fascicularis). The tracers used were [11C]PE2I, [11C]DOPA, [11C]raclopride for monitoring dopamine transporter (DAT) densities, dopamine (DA) turnover, dopamine D2-receptor (D2R) densities, respectively. The gross behavioral observation was also performed referring to the criteria of the PD symptoms. The motor dysfunction was not clearly observed up to the cumulative doses of 3 mg/kg MPTP. This period was called 'asymptomatic period'. As a result of PET scans in the asymptomatic period, DAT densities and DA turnover had already decreased greatly, but D2R densities had not changed clearly. These findings suggest that PET imaging can delineate the dopaminergic dysfunction in vivo even in the asymptomatic period. In human study of PD, it is reported that parkinsonism is shown after great loss of dopaminergic neutrons as well as pre-synaptic dysfunction. MPTP-treated monkeys demonstrate the parkinsonian syndrome with the similar mechanism as human PD. It can be expected that PET study with MPTP-monkeys would provide important clues relevant to the underlying cause of PD and be useful for preclinical study of regenerative medicine in this disease. (author)

Is visual assessment of thyroid attenuation on unenhanced CT of the chest useful for detecting hypothyroidism?

Science.gov (United States)

Maldjian, P D; Chen, T

2016-11-01

To determine if visual assessment of the attenuation of morphologically normal appearing thyroid glands on unenhanced computed tomography (CT) of the chest is useful for identifying patients with decreased thyroid function. This was a retrospective study of 765 patients who underwent both unenhanced CT of the chest and thyroid function tests performed within 1 year of the CT examination. Attenuation of the thyroid gland was visually assessed in each patient relative to the attenuation of the surrounding muscles to categorise the gland as "low attenuation" (attenuation similar to surrounding muscles) or "high attenuation" (attenuation greater than surrounding muscles). Thyroid attenuation was quantitatively measured in each case to determine the validity of the visual assessment. Results of thyroid function tests were used to classify thyroid function as hypothyroid, euthyroid, or hyperthyroid. Data were analysed to determine the relationship between visual assessment of thyroid attenuation and status of thyroid function. Thyroid glands of low attenuation were present in 4.2% (32/765) of the patients. Nearly half (47%) of the patients with low-attenuation thyroids had hypofunctioning thyroid glands. Compared to patients with high-attenuation thyroids, patients with low-attenuation thyroids were significantly more likely to have decreased thyroid function (clinical and subclinical hypothyroidism) and significantly less likely to be euthyroid (p<0.0001). Quantitative measurement of thyroid attenuation confirmed the validity of the visual assessment. Low attenuation of an otherwise normal-appearing thyroid gland on unenhanced CT of the chest is strongly associated with decreased thyroid function. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

The Self Attenuation Correction for Holdup Measurements, a Historical Perspective

International Nuclear Information System (INIS)

Oberer, R. B.; Gunn, C. A.; Chiang, L. G.

2006-01-01

Self attenuation has historically caused both conceptual as well as measurement problems. The purpose of this paper is to eliminate some of the historical confusion by reviewing the mathematical basis and by comparing several methods of correcting for self attenuation focusing on transmission as a central concept

Transmission-less attenuation estimation from time-of-flight PET histo-images using consistency equations

Science.gov (United States)

Li, Yusheng; Defrise, Michel; Metzler, Scott D.; Matej, Samuel

2015-08-01

In positron emission tomography (PET) imaging, attenuation correction with accurate attenuation estimation is crucial for quantitative patient studies. Recent research showed that the attenuation sinogram can be determined up to a scaling constant utilizing the time-of-flight information. The TOF-PET data can be naturally and efficiently stored in a histo-image without information loss, and the radioactive tracer distribution can be efficiently reconstructed using the DIRECT approaches. In this paper, we explore transmission-less attenuation estimation from TOF-PET histo-images. We first present the TOF-PET histo-image formation and the consistency equations in the histo-image parameterization, then we derive a least-squares solution for estimating the directional derivatives of the attenuation factors from the measured emission histo-images. Finally, we present a fast solver to estimate the attenuation factors from their directional derivatives using the discrete sine transform and fast Fourier transform while considering the boundary conditions. We find that the attenuation histo-images can be uniquely determined from the TOF-PET histo-images by considering boundary conditions. Since the estimate of the attenuation directional derivatives can be inaccurate for LORs tangent to the patient boundary, external sources, e.g. a ring or annulus source, might be needed to give an accurate estimate of the attenuation gradient for such LORs. The attenuation estimation from TOF-PET emission histo-images is demonstrated using simulated 2D TOF-PET data.

Phase Aberration and Attenuation Effects on Acoustic Radiation Force-Based Shear Wave Generation.

Science.gov (United States)

Carrascal, Carolina Amador; Aristizabal, Sara; Greenleaf, James F; Urban, Matthew W

2016-02-01

Elasticity is measured by shear wave elasticity imaging (SWEI) methods using acoustic radiation force to create the shear waves. Phase aberration and tissue attenuation can hamper the generation of shear waves for in vivo applications. In this study, the effects of phase aberration and attenuation in ultrasound focusing for creating shear waves were explored. This includes the effects of phase shifts and amplitude attenuation on shear wave characteristics such as shear wave amplitude, shear wave speed, shear wave center frequency, and bandwidth. Two samples of swine belly tissue were used to create phase aberration and attenuation experimentally. To explore the phase aberration and attenuation effects individually, tissue experiments were complemented with ultrasound beam simulations using fast object-oriented C++ ultrasound simulator (FOCUS) and shear wave simulations using finite-element-model (FEM) analysis. The ultrasound frequency used to generate shear waves was varied from 3.0 to 4.5 MHz. Results: The measured acoustic pressure and resulting shear wave amplitude decreased approximately 40%-90% with the introduction of the tissue samples. Acoustic intensity and shear wave displacement were correlated for both tissue samples, and the resulting Pearson's correlation coefficients were 0.99 and 0.97. Analysis of shear wave generation with tissue samples (phase aberration and attenuation case), measured phase screen, (only phase aberration case), and FOCUS/FEM model (only attenuation case) showed that tissue attenuation affected the shear wave generation more than tissue aberration. Decreasing the ultrasound frequency helped maintain a focused beam for creation of shear waves in the presence of both phase aberration and attenuation.

Implementation of a monitoring protocol for the natural attenuation of soil

International Nuclear Information System (INIS)

Setier, J.C.; Pornain, J.L.; Millette, D.; Perie, F.; Deschenes, L.; Samson, R.

2005-01-01

Large quantities of hydrocarbons are extracted, produced, refined, and transported each year. Despite environmental procedures that are used in industry, the risk of environmental degradation cannot be avoided. Furthermore, aging installations can also present residual contamination. Some of these sites must be decontaminated to residual levels of soil contaminants that are established through discussions with national authorities. These levels are set with respect to the intended use of the site. For several years now, the evaluation of the risk of a contaminant in a particular environment must take into account land use. For certain sites that do not present direct risks for the surrounding environment, natural attenuation offers an interesting alternative to costly remediation strategies. In order to determine whether natural attenuation is a technique suited for soil restoration, TOTAL Exploration Production launched a research project on natural attenuation in 1997. By natural attenuation, we refer to all the processes that act to reduce the concentrations of contaminants in soil (i.e. biotic and abiotic mechanisms). The research project consists of two main components: - The development of decision-making tools designed to evaluate the potential for natural attenuation of hydrocarbons. These software programs, named SITE I and SITE II and developed by the Industrial Chair in Site Remediation and Management of the Ecole Polytechnique de Montreal take into account microbial and biotic processes involved the natural attenuation of contaminants in groundwater (SITE I) and soil (SITE II). - The set-up of a pilot-scale demonstration of natural attenuation in soils within the vadose zone at a refinery belonging to the TOTAL group. This pilot project, done in collaboration with the NSERC Industrial Chair in Site Remediation and Management of the Ecole Polytechnique de Montreal, has the following objectives : 1. Evaluation of the feasibility of natural attenuation as

Novel Intriguing Strategies Attenuating to Sarcopenia

Directory of Open Access Journals (Sweden)

Kunihiro Sakuma

2012-01-01

Full Text Available Sarcopenia, the age-related loss of skeletal muscle mass, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, increased risk of fall-related injury, and, often, frailty. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for drug discovery. Resistance training combined with amino acid-containing supplements is often utilized to prevent age-related muscle wasting and weakness. In this review, we summarize more recent therapeutic strategies (myostatin or proteasome inhibition, supplementation with eicosapentaenoic acid (EPA or ursolic acid, etc. for counteracting sarcopenia. Myostatin inhibitor is the most advanced research with a Phase I/II trial in muscular dystrophy but does not try the possibility for attenuating sarcopenia. EPA and ursolic acid seem to be effective as therapeutic agents, because they attenuate the degenerative symptoms of muscular dystrophy and cachexic muscle. The activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α in skeletal muscle by exercise and/or unknown supplementation would be an intriguing approach to attenuating sarcopenia. In contrast, muscle loss with age may not be influenced positively by treatment with a proteasome inhibitor or antioxidant.

Seismic attenuation structure beneath Nazca Plate subduction zone in southern Peru

Science.gov (United States)

Jang, H.; Kim, Y.; Clayton, R. W.

2017-12-01

We estimate seismic attenuation in terms of quality factors, QP and QS using P and S phases, respectively, beneath Nazca Plate subduction zone between 10°S and 18.5°S latitude in southern Peru. We first relocate 298 earthquakes with magnitude ranges of 4.0-6.5 and depth ranges of 20-280 km. We measure t*, which is an integrated attenuation through the seismic raypath between the regional earthquakes and stations. The measured t* are inverted to construct three-dimensional attenuation structures of southern Peru. Checkerboard test results for both QP and QS structures ensure good resolution in the slab-dip transition zone between flat and normal slab subduction down to a depth of 200 km. Both QP and QS results show higher attenuation continued down to a depth of 50 km beneath volcanic arc and also beneath the Quimsachata volcano, the northernmost young volcano, located far east of the main volcanic front. We also observe high attenuation in mantle wedge especially beneath the normal subduction region in both QP and QS (100-130 in QP and 100-125 in QS) and slightly higher QP and QS beneath the flat-subduction and slab-dip transition regions. We plan to relate measured attenuation in the mantle wedge to material properties such as viscosity to understand the subduction zone dynamics.

Effectiveness of computed tomography attenuation values in characterization of pericardial effusion.

Science.gov (United States)

Çetin, Mehmet Serkan; Özcan Çetin, Elif Hande; Özdemir, Mustafa; Topaloğlu, Serkan; Aras, Dursun; Temizhan, Ahmet; Aydoğdu, Sinan

2017-04-01

The aim of this study was to evaluate the effectiveness of computed tomography (CT) attenuation values in the characterization of pericardial effusion. This study consisted of 96 patients with pericardial effusion who underwent pericardiocentesis. For further diagnostic evaluation of pericardial effusion, all the patients were assessed by thorax CT. CT attenuation values were measured from at least 5 different areas of pericardial fluid by specifying the largest region of interest. The average of these measurements was computed and considered as the CT attenuation value of the patient. The patients were classified into two groups: patients with transudative pericardial effusion and those with exudative pericardial effusion. CT attenuation values were significantly higher in patients with exudative pericardial effusion than in those with transudative pericardial effusion [14.85±10.7 Hounsfield unit (HU) vs. 1.13±4.3 HU, peffusion. In addition, a cut-off value of 6.5 HU had 71.4% sensitivity and 72.3% specificity for the prediction of cardiac tamponade. In patients with pericardial effusion, CT attenuation values seem to be correlated with the characterization parameters of the fluid and may distinguish exudative pericardial effusion from transudative pericardial effusion. This parameter was also found to be a predictor of cardiac tamponade. CT attenuation values can be a useful tool in the clinical evaluation of patients with pericardial effusion.

Autoradiography of [14C]paraquat or [14C]diquat in frogs and mice: accumulation in neuromelanin

International Nuclear Information System (INIS)

Lindquist, N.G.; Larsson, B.S.; Lyden-Sokolowski, A.

1988-01-01

The herbicide paraquat has been suggested as a causative agent for Parkinson's disease because of its structural similarity to a metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which may induce a parkinsonism-like condition. MPTP as well as its metabolite 1-methyl-4-phenylpyridine have melanin affinity, and the parkinsonism-inducing potency of MPTP is much stronger in species with melanin in the nerve cells. Autoradiography of [ 3 H]MPTP in experimental animals has shown accumulation in melanin-containing tissues, including pigmented neurons. In the present whole body autoradiographic study accumulation and retention was seen in neuromelanin in frogs after i.p. injection of [ 14 C]paraquat or[ 14 C]diquat. By means of whole body autoradiography of [ 14 C]diquat in mice (a species with no or very limited amounts of neuromelanin) a low, relatively uniformly distributed level of radioactivity was observed in brain tissue. Accumulation of toxic chemical compounds, such as paraquat, in neuromelanin may ultimately cause lesions in the pigmented nerve cells, leading to Parkinson's disease

The 5-HT2A receptor antagonist M100907 produces antiparkinsonian effects and decreases striatal glutamate

Directory of Open Access Journals (Sweden)

Twum eAnsah

2011-06-01

Full Text Available 5-HT plays a regulatory role in voluntary movements of the basal ganglia and have a major impact on disorders of the basal ganglia such as Parkinson’s disease (PD. Clinical studies have suggested that 5-HT2 receptor antagonists may be useful in the treatment of the motor symptoms of PD. We hypothesized that 5-HT2A receptor antagonists may restore motor function by regulating glutamatergic activity in the striatum. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP exhibited decreased performance on the beam-walking apparatus. Peripheral administration of the 5-HT2A receptor antagonist M100907 improved performance of MPTP-treated mice on the beam-walking apparatus. In vivo microdialysis revealed an increase in striatal extracellular glutamate in MPTP-treated mice and local perfusion of M100907 into the dorsal striatum significantly decreased extracellular glutamate levels in saline and MPTP-treated mice. Our studies suggest that blockade of 5-HT2A receptors may represent a novel therapeutic target for the motor symptoms of Parkinson’s disease.

Curcumin inhibition of JNKs prevents dopaminergic neuronal loss in a mouse model of Parkinson’s disease through suppressing mitochondria dysfunction

Directory of Open Access Journals (Sweden)

Pan Jing

2012-08-01

Full Text Available Abstract Curcumin,a natural polyphenol obtained from turmeric,has been implicated to be neuroprotective in a variety of neurodegenerative disorders although the mechanism remains poorly understood. The results of our recent experiments indicated that curcumin could protect dopaminergic neurons from apoptosis in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mouse model of Parkinson’s disease (PD. The death of dopaminergic neurons and the loss of dopaminergic axon in the striatum were significantly suppressed by curcumin in MPTP mouse model. Further studies showed that curcumin inhibited JNKs hyperphosphorylation induced by MPTP treatment. JNKs phosphorylation can cause translocation of Bax to mitochondria and the release of cytochrome c which both ultimately contribute to mitochondria-mediated apoptosis. These pro-apoptosis effect can be diminished by curcumin. Our experiments demonstrated that curcumin can prevent nigrostriatal degeneration by inhibiting the dysfunction of mitochondrial through suppressing hyperphosphorylation of JNKs induced by MPTP. Our results suggested that JNKs/mitochondria pathway may be a novel target in the treatment of PD patients.

Autoradiography of ( sup 14 C)paraquat or ( sup 14 C)diquat in frogs and mice: accumulation in neuromelanin

Energy Technology Data Exchange (ETDEWEB)

Lindquist, N G; Larsson, B S; Lyden-Sokolowski, A [Uppsala Univ., Biomedical Center, (Sweden). Dept. of Toxicology

1988-10-31

The herbicide paraquat has been suggested as a causative agent for Parkinson's disease because of its structural similarity to a metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which may induce a parkinsonism-like condition. MPTP as well as its metabolite 1-methyl-4-phenylpyridine have melanin affinity, and the parkinsonism-inducing potency of MPTP is much stronger in species with melanin in the nerve cells. Autoradiography of ({sup 3}H)MPTP in experimental animals has shown accumulation in melanin-containing tissues, including pigmented neurons. In the present whole body autoradiographic study accumulation and retention was seen in neuromelanin in frogs after i.p. injection of ({sup 14}C)paraquat or({sup 14}C)diquat. By means of whole body autoradiography of ({sup 14}C)diquat in mice (a species with no or very limited amounts of neuromelanin) a low, relatively uniformly distributed level of radioactivity was observed in brain tissue. Accumulation of toxic chemical compounds, such as paraquat, in neuromelanin may ultimately cause lesions in the pigmented nerve cells, leading to Parkinson's disease.

Effective x-ray attenuation measurements with full field digital mammography

International Nuclear Information System (INIS)

Heine, John J.; Behera, Madhusmita

2006-01-01

This work shows that effective x-ray attenuation coefficients may be estimated by applying Beer's Law to phantom image data acquired with the General Electric Senographe 2000D full field digital mammography system. Theoretical developments are provided indicating that an approximate form of the Beer's relation holds for polychromatic x-ray beams. The theoretical values were compared with experimentally determined measured values, which were estimated at various detector locations. The measured effective attenuation coefficients are in agreement with those estimated with theoretical developments and numerical integration. The work shows that the measured quantities show little spatial variation. The main ideas are demonstrated with polymethylmethacrylate and breast tissue equivalent phantom imaging experiments. The work suggests that the effective attenuation coefficients may be used as known values for radiometric standardization applications that compensate for the image acquisition influences. The work indicates that it is possible to make quantitative attenuation coefficient measurements from a system designed for clinical purposes

Enhanced Attenuation: Chlorinated Organics

Science.gov (United States)

2008-04-01

attenuation capacity of the aquifer downgradient from the source (e.g., permeable reactive barriers or phytoremediation ) Selection of EA remedies should be...prevalence and/or mobility of nitrate and sulfate compounds and/or metals such as iron, manganese, chromium, copper, and arsenic . Furthermore, in...ranging from very aggressive source destruction and removal methods to less energy-intensive methods, such as phytoremediation . In many cases, it

Measurement of attenuation coefficients of the fundamental and second harmonic waves in water

Science.gov (United States)

Zhang, Shuzeng; Jeong, Hyunjo; Cho, Sungjong; Li, Xiongbing

2016-02-01

Attenuation corrections in nonlinear acoustics play an important role in the study of nonlinear fluids, biomedical imaging, or solid material characterization. The measurement of attenuation coefficients in a nonlinear regime is not easy because they depend on the source pressure and requires accurate diffraction corrections. In this work, the attenuation coefficients of the fundamental and second harmonic waves which come from the absorption of water are measured in nonlinear ultrasonic experiments. Based on the quasilinear theory of the KZK equation, the nonlinear sound field equations are derived and the diffraction correction terms are extracted. The measured sound pressure amplitudes are adjusted first for diffraction corrections in order to reduce the impact on the measurement of attenuation coefficients from diffractions. The attenuation coefficients of the fundamental and second harmonics are calculated precisely from a nonlinear least squares curve-fitting process of the experiment data. The results show that attenuation coefficients in a nonlinear condition depend on both frequency and source pressure, which are much different from a linear regime. In a relatively lower drive pressure, the attenuation coefficients increase linearly with frequency. However, they present the characteristic of nonlinear growth in a high drive pressure. As the diffraction corrections are obtained based on the quasilinear theory, it is important to use an appropriate source pressure for accurate attenuation measurements.

Evaluation of downwelling diffuse attenuation coefficient algorithms in the Red Sea

KAUST Repository

Tiwari, Surya Prakash; Yellepeddi, Sarma B.; Jones, Burton

2016-01-01

to comprehend the diffuse attenuation coefficient and its relationship with in situ properties. Two apparent optical properties, spectral remote sensing reflectance (Rrs) and the downwelling diffuse attenuation coefficient (Kd), are calculated from vertical

Role for excitatory amino acids in methamphetamine-induced nigrostriatal dopaminergic toxicity.

Science.gov (United States)

Sonsalla, P K; Nicklas, W J; Heikkila, R E

1989-01-20

The systemic administration of either methamphetamine or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to experimental animals produces degenerative changes in nigrostriatal dopaminergic neurons or their axon terminals. This study was conducted to determine if excitatory amino acids, which appear to be involved in various neurodegenerative disorders, might also contribute to the dopaminergic neurotoxicity produced in mice by either methamphetamine or MPTP. MK-801, phencyclidine, and ketamine, noncompetitive antagonists of one subtype of excitatory amino acid receptor, the N-methyl-D-aspartate receptor, provided substantial protection against neurotoxicity produced by methamphetamine but not that produced by MPTP. These findings indicate that excitatory amino acids play an important role in the nigrostriatal dopaminergic damage induced by methamphetamine.

Rolipram improves facilitation of contextual fear extinction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease

Directory of Open Access Journals (Sweden)

Ken-ichi Kinoshita

2017-05-01

Full Text Available Cognitive impairment often occurs in Parkinson's disease (PD, but the mechanism of onset remains unknown. Recently, we reported that PD model mice produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP show facilitation of hippocampal memory extinction, which may be the cause of cognitive impairment in PD. When we examined the cAMP/CREB signaling in the hippocampus, decreased levels of cAMP and phosphorylated CREB were observed in the dentate gyrus (DG of MPTP-treated mice. Administration of rolipram improved the memory deficits with concomitant recovery of cAMP and phosphorylated CREB levels, suggesting that reduced cAMP/CREB signaling in the DG leads to cognitive impairment in MPTP-treated mice.

Implication of seismic attenuation for gas hydrate resource characterization, Mallik, Mackenzie Delta, Canada

Science.gov (United States)

Bellefleur, G.; Riedel, M.; Brent, T.; Wright, F.; Dallimore, S. R.

2007-10-01

Wave attenuation is an important physical property of hydrate-bearing sediments that is rarely taken into account in site characterization with seismic data. We present a field example showing improved images of hydrate-bearing sediments on seismic data after compensation of attenuation effects. Compressional quality factors estimated from zero-offset Vertical Seismic Profiling data acquired at Mallik, Northwest Territories, Canada, demonstrate significant wave attenuation for hydrate-bearing sediments. These results are in agreement with previous attenuation estimates obtained from sonic logs and crosshole data at different frequency intervals. The application of an inverse Q-filter to compensate attenuation effects of permafrost and hydrate-bearing sediments improved the resolution of surface 3D seismic data and its correlation with log data, particularly for the shallowest gas hydrate interval. Compensation of the attenuation effects of the permafrost likely explains most of the improvements for the shallow gas hydrate zone. Our results show that characterization of the Mallik gas hydrates with seismic data not corrected for attenuation would tend to overestimate thicknesses and lateral extent of hydrate-bearing strata and hence, the volume of hydrates in place.

Detecting The EBL Attenuation Of Blazars With GLAST

Science.gov (United States)

Reyes, Luis C.

2006-09-01

The Large Area Telescope (LAT) on board GLAST (Gamma-ray Large Area Space Telescope) due for launch in Fall 2007 will study the gamma-ray sky in the energy range 20 MeV to >300 GeV. GLAST-LAT's improved sensitivity with respect to previous missions will increase the number of known Blazars from about 100 to thousands, with redshifts up to z 5. Since Gamma rays with energy above 10 GeV interact via pair-production with photons from the Extragalactic Background Light (EBL), the systematic attenuation of GLAST-detected Blazars as a function of redshift would constitute and effective and unique probe to the optical-UV EBL density and its evolution over cosmic history. Based on the GLAST-LAT instrument performance, detailed simulations of expected blazar populations attenuated by EBL have been performed. In this poster we present an analysis of such simulations in order to measure the EBL attenuation, ensuing a clear distinction between competing EBL models.

Ultrasonic attenuation of CdSe at low temperatures

Energy Technology Data Exchange (ETDEWEB)

Fernandez, B.J., E-mail: braulio@ula.v [Centro de Estudios de Semiconductores, Departamento de Fisica, Facultad de Ciencias, Universidad de Los Andes Apartado de Correos No.1, La Hechicera, Merida 5251 (Venezuela, Bolivarian Republic of); Calderon, E.; Bracho, D.B. [Centro de Estudios de Semiconductores, Departamento de Fisica, Facultad de Ciencias, Universidad de Los Andes Apartado de Correos No.1, La Hechicera, Merida 5251 (Venezuela, Bolivarian Republic of); Perez, J.F. [Laboratorio de Instrumentacion Cientifica, Facultad de Ciencias, Universidad de Los Andes Apartado de Correos No.1, La Hechicera, Merida 5251 (Venezuela, Bolivarian Republic of)

2010-08-01

The ultrasonic attenuation of a single crystal of CdSe has been investigated over the temperature range from 1.2 to 300 K at frequencies of 10, 30 and 90 MHz. We report here the temperature dependence of the attenuation in the range 1.2-30 K for piezoactive and non-piezoactive acoustic waves. A temperature-induced relaxation for two piezoactive waves, which scale with frequency towards higher temperatures, was found. A modified Hutson and White model with a new parameter {gamma} is proposed to explain the relaxation maxima of our data and others in the literature. In this model the parameter {gamma}, which seems to be closely related to the compensation, takes into account the impurities-sound wave piezoelectric coupling. By inverting the proposed expression for the sound attenuation to obtain the electrical conductivity from the relaxation, it is found that impurity conductivity of the hopping type is the dominant conduction process at low temperatures.

Ultrasonic attenuation of CdSe at low temperatures

International Nuclear Information System (INIS)

Fernandez, B.J.; Calderon, E.; Bracho, D.B.; Perez, J.F.

2010-01-01

The ultrasonic attenuation of a single crystal of CdSe has been investigated over the temperature range from 1.2 to 300 K at frequencies of 10, 30 and 90 MHz. We report here the temperature dependence of the attenuation in the range 1.2-30 K for piezoactive and non-piezoactive acoustic waves. A temperature-induced relaxation for two piezoactive waves, which scale with frequency towards higher temperatures, was found. A modified Hutson and White model with a new parameter γ is proposed to explain the relaxation maxima of our data and others in the literature. In this model the parameter γ, which seems to be closely related to the compensation, takes into account the impurities-sound wave piezoelectric coupling. By inverting the proposed expression for the sound attenuation to obtain the electrical conductivity from the relaxation, it is found that impurity conductivity of the hopping type is the dominant conduction process at low temperatures.

Plasmodium yoelii: induction of attenuated mutants by irradiation

International Nuclear Information System (INIS)

Waki, S.; Yonome, I.; Suzuki, M.

1986-01-01

When erythrocytic forms of Plasmodium yoelii nigeriensis, which is invariably fatal in mice, were exposed to X rays, the dose to reduce surviving parasites to one millionth was 100 gray (10 Krad). A suspension of 5 X 10(6) per ml of parasitized erythrocyte was irradiated at 100 gray, and 0.2 ml aliquots were inoculated into 22 mice. Eleven mice showed patent parasitemia, and in these the growth curves were less steep than that found in nonirradiated parasites. The infections of 8 mice of the 11 were self-resolving, and the attenuated feature of the parasites maintained following a limited number of blood passages. The parasites were slowly growing even in nude mice and cause self-resolving infections in intact mice. BALB/c mice immunized with the attenuated parasites were protected against subsequent challenge infections with the original virulent erythrocytic and sporogonic forms. These findings indicate that attenuated mutants of malaria parasites can be readily induced by this method

Intensity attenuation relation at Chamba–Garhwal area in north-west ...

Indian Academy of Sciences (India)

Seismic hazard assessment of any region depends on the attenuation relation ... The present study includes 10 moderate and major earthquakes (Ms ≥ 4.9) that had occurred during the ... city and attenuation of strong seismic ground motion. ... Seismologists have benefitted from the development .... In that case, we inferred.

Compact plasmonic variable optical attenuator

DEFF Research Database (Denmark)

Leosson, Kristjan; Rosenzveig, Tiberiu; Hermannsson, Pétur Gordon

2008-01-01

We demonstrate plasmonic nanowire-based thermo-optic variable optical attenuators operating in the 1525-1625 nm wavelength range. The devices have a footprint as low as 1 mm, extinction ratio exceeding 40 dB, driving voltage below 3 V, and full modulation bandwidth of 1 kHz. The polarization...

Derivation of linear attenuation coefficients from CT numbers for low-energy photons

International Nuclear Information System (INIS)

Watanabe, Y.

1999-01-01

One can estimate photon attenuation properties from the CT number. In a standard method one assumes that the linear attenuation coefficient is proportional to electron density and ignores its nonlinear dependence on atomic number. When the photon energy is lower than about 50 keV, such as for brachytherapy applications, however, photoelectric absorption and Rayleigh scattering become important. Hence the atomic number must be explicitly considered in estimating the linear attenuation coefficient. In this study we propose a method to more accurately estimate the linear attenuation coefficient of low-energy photons from CT numbers. We formulate an equation that relates the CT number to the electron density and the effective atomic number. We use a CT calibration phantom to determine unknown coefficients in the equation. The equation with a given CT number is then solved for the effective atomic number, which in turn is used to calculate the linear attenuation coefficient for low-energy photons. We use the CT phantom to test the new method. The method significantly improves the standard method in estimating the attenuation coefficient at low photon energies (20keV≤E≤40keV) for materials with high atomic numbers. (author)

Oesophagostomum columbianum : immunization of young lambs using gamma ray attenuated inefective larvae

International Nuclear Information System (INIS)

Sharma, R.L.; Dhar, D.N.

1987-01-01

Infective Oesophagostomum columbianum larvae were successfully attenuated by exposing them to a gamma radiation dose levels of either 40 or 50 Krad. Lambs receiving a single vaccination dose of 2000 infective larvae attenuated at 40 Krad developed partial protection, whereas those vaccinated with similar dose of infection with 50 Krad irradiated larvae failed to develop any protection. A double vaccination schedule comprising of 500 and 2000 gamma attenuated (40 Krad) infective larvae induced a significantly higher level of protection against the challenge dose. The possible use of radiation attenuated larvae as vaccine for immunoprophylaxis against ovine Oesophagostomiasis has been discussed. (author). 11 refs., 2 tables

Seismic wave attenuation and velocity dispersion in UAE carbonates

Science.gov (United States)

Ogunsami, Abdulwaheed Remi

Interpreting the seismic property of fluids in hydrocarbon reservoirs at low frequency scale has been a cherished goal of petroleum geophysics research for decades. Lately, there has been tremendous interest in understanding attenuation as a result of fluid flow in porous media. Although interesting, the emerging experimental and theoretical information still remain ambiguous and are practically not utilized for reasons not too obscure. Attenuation is frequency dependent and hard to measure in the laboratory at low frequency. This thesis describes and reports the results of an experimental study of low frequency attenuation and velocity dispersion on a selected carbonate reservoir samples in the United Arab Emirates (UAE). For the low frequency measurements, stress-strain method was used to measure the moduli from which the velocity is derived. Attenuation was measured as the phase difference between the applied stress and the strain. For the ultrasonic component, the pulse propagation method was employed. To study the fluid effect especially at reservoir in situ conditions, the measurements were made dry and saturated with liquid butane and brine at differential pressures of up to 5000 psi with pore pressure held constant at 500 psi. Similarly to what has been documented in the literatures for sandstone, attenuation of the bulk compressibility mode dominates the losses in these dry and somewhat partially saturated carbonate samples with butane and brine. Overall, the observed attenuation cannot be simply said to be frequency dependent within this low seismic band. While attenuation seems to be practically constant in the low frequency band for sample 3H, such conclusion cannot be made for sample 7H. For the velocities, significant dispersion is observed and Gassmann generally fails to match the measured velocities. Only the squirt model fairly fits the velocities, but not at all pressures. Although the observed dispersion is larger than Biot's prediction, the fact

The role of mitochondria in protection of the heart by preconditioning

Science.gov (United States)

Halestrap, Andrew P.; Clarke, Samantha J.; Khaliulin, Igor

2007-01-01

A prolonged period of ischaemia followed by reperfusion irreversibly damages the heart. Such reperfusion injury (RI) involves opening of the mitochondrial permeability transition pore (MPTP) under the conditions of calcium overload and oxidative stress that accompany reperfusion. Protection from MPTP opening and hence RI can be mediated by ischaemic preconditioning (IP) where the prolonged ischaemic period is preceded by one or more brief (2–5 min) cycles of ischaemia and reperfusion. Following a brief overview of the molecular characterisation and regulation of the MPTP, the proposed mechanisms by which IP reduces pore opening are reviewed including the potential roles for reactive oxygen species (ROS), protein kinase cascades, and mitochondrial potassium channels. It is proposed that IP-mediated inhibition of MPTP opening at reperfusion does not involve direct phosphorylation of mitochondrial proteins, but rather reflects diminished oxidative stress during prolonged ischaemia and reperfusion. This causes less oxidation of critical thiol groups on the MPTP that are known to sensitise pore opening to calcium. The mechanisms by which ROS levels are decreased in the IP hearts during prolonged ischaemia and reperfusion are not known, but appear to require activation of protein kinase Cε, either by receptor-mediated events or through transient increases in ROS during the IP protocol. Other signalling pathways may show cross-talk with this primary mechanism, but we suggest that a role for mitochondrial potassium channels is unlikely. The evidence for their activity in isolated mitochondria and cardiac myocytes is reviewed and the lack of specificity of the pharmacological agents used to implicate them in IP is noted. Some K+ channel openers uncouple mitochondria and others inhibit respiratory chain complexes, and their ability to produce ROS and precondition hearts is mimicked by bona fide uncouplers and respiratory chain inhibitors. IP may also provide continuing

Photon attenuation properties of some thorium, uranium and plutonium compounds

Energy Technology Data Exchange (ETDEWEB)

Singh, V. P.; Badiger, N. M. [Karnatak University, Department of Physics, Dharwad-580003, Karnataka (India); Vega C, H. R., E-mail: kudphyvps@rediffmail.com [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas, Zac. (Mexico)

2015-10-15

Mass attenuation coefficients, effective atomic numbers, effective electron densities for nuclear materials; thorium, uranium and plutonium compounds have been studied. The photon attenuation properties for the compounds have been investigated for partial photon interaction processes by photoelectric effect, Compton scattering and pair production. The values of these parameters have been found to change with photon energy and interaction process. The variations of mass attenuation coefficients, effective atomic number and electron density with energy are shown graphically. Moreover, results have shown that these compounds are better shielding and suggesting smaller dimensions. The study would be useful for applications of these materials for gamma ray shielding requirement. (Author)

Fast neutron attenuation measurements for detection of illicit materials

International Nuclear Information System (INIS)

Lee, Hee Seock; Chung, Chin Wha; Guon, Ki Il; Lee, Bo Young; Ko, Seung Kook; Shin, Yong Mu

2002-01-01

Experiments were carried out to develop a novel method using neutron attenuation for the detection of illicit materials. By using pulsed fast neutrons generated from a Bi target bombarded with a 2 GeV electron beam, attenuation spectra of C, N, and O have been measured to study the feasibility of a practical application. The spectral dependence on the material thickness and the geometrical distribution as well as the ability to identify different elements in a layered environment have been studied. For the elements mentioned here, the total cross sections have been obtained from the measured attenuation spectra and compared with ENDF-VI, which showed good agreement. The study confirms that a conventional low energy electron linac can be put into a practical use, and some practical idea is presented

Multiple-energy tissue-cancellation applications of a digital beam attenuator to chest radiography

International Nuclear Information System (INIS)

Dobbins, J.T. III.

1985-01-01

The digitally-formed primary beam attenuator (DBA) spatially modulates the x-ray fluence incident upon the patient to selectively attenuate regions of interest. The DBA attenuating mask is constructed from CeO 2 powder by a modified printing technique and uses image information from an initial low-dose exposure. Two tissue-cancellation imaging techniques are investigated with the DBA: (1) energy-dependent information is used to form a beam attenuator that attenuates specific tissues in the primary x-ray beam for tissue-cancelled film radiography; (2) the beam attenuator is used to improve image signal-to-noise and scattered radiation properties in traditional energy-subtraction tissue-cancellation imaging with digital detectors. The tissue-cancellation techniques in the primary x-ray beam were capable of adequately removing either soft-tissue or bone from the final compensated film radiograph when using a phantom with well defined soft-tissue and bone sections. However, when tried on an anthropomorphic chest phantom the results were adequate for cancellation of large soft tissue structures, but unsatisfactory for cancellation of bony structures such as the ribs, because of the limited spatial frequency content of the attenuating mask. The second technique (with digital detectors) showed improved uniformity of image signal-to-noise and a two-fold increase in soft-tissue nodule contrast due to improved scattered radiation properties. The tissue-cancelled images contained residual image contributions from the presence of the attenuating mask, but this residual may be correctable by future algorithms

The Ultraviolet Attenuation Law in Backlit Spiral Galaxies

Science.gov (United States)

Keel, William C.; Manning, Anna M.; Holwerda, Benne W.; Lintott, Chris J.; Schawinski, Kevin

2014-02-01

The effective extinction law (attenuation behavior) in galaxies in the emitted ultraviolet (UV) regime is well known only for actively star-forming objects and combines effects of the grain properties, fine structure in the dust distribution, and relative distributions of stars and dust. We use Galaxy Evolution Explorer, XMM Optical Monitor, and Hubble Space Telescope (HST) data to explore the UV attenuation in the outer parts of spiral disks which are backlit by other UV-bright galaxies, starting with the candidate list of pairs provided by Galaxy Zoo participants. New optical images help to constrain the geometry and structure of the target galaxies. Our analysis incorporates galaxy symmetry, using non-overlapping regions of each galaxy to derive error estimates on the attenuation measurements. The entire sample has an attenuation law across the optical and UV that is close to the Calzetti et al. form; the UV slope for the overall sample is substantially shallower than found by Wild et al., which is a reasonable match to the more distant galaxies in our sample but not to the weighted combination including NGC 2207. The nearby, bright spiral NGC 2207 alone gives an accuracy almost equal to the rest of our sample, and its outer arms have a very low level of foreground starlight. Thus, this widespread, fairly "gray" law can be produced from the distribution of dust alone, without a necessary contribution from differential escape of stars from dense clouds. Our results indicate that the extrapolation needed to compare attenuation between backlit galaxies at moderate redshifts from HST data, and local systems from Sloan Digital Sky Survey and similar data, is mild enough to allow the use of galaxy overlaps to trace the cosmic history of dust in galaxies. For NGC 2207, HST data in the near-UV F336W band show that the covering factor of clouds with small optical attenuation becomes a dominant factor farther into the UV, which opens the possibility that widespread

analysis of rain rate and rain attenuation for earth-space

African Journals Online (AJOL)

Rain rate and rain attenuation predictions are vital when designing microwave satellite and terrestrial communication links, such as in the Ku and Ka bands. This paper presents the cumulative distribution functions (CDFs) of the predicted rain rate and rain attenuation for Uyo, Akwa Ibom State (AKS) (Latitude: 4.88°N, ...

Ketoconazole attenuates radiation-induction of tumor necrosis factor

Energy Technology Data Exchange (ETDEWEB)

Hallahan, D.E.; Virudachalam, S.; Kufe, D.W.; Weichselbaum, R.R. [Dana Farber Cancer Institute, Boston, MA (United States)

1994-07-01

Previous work has demonstrated that inhibitors of phospholipase A2 attenuate ionizing radiation-induced arachidonic acid production, protein kinase C activation, and prevent subsequent induction of the tumor necrosis factor gene. Because arachidonic acid contributes to radiation-induced tumor necrosis factor expression, the authors analyzed the effects of agents which alter arachidonate metabolism on the regulation of this gene. Phospholipase A2 inhibitors quinicrine, bromphenyl bromide, and pentoxyfylline or the inhibitor of lipoxygenase (ketoconazole) or the inhibitor of cycloxygenase (indomethacine) were added to cell culture 1 h prior to irradiation. Radiation-induced tumor necrosis factor gene expression was attenuated by each of the phospholipase A2 inhibitors (quinicrine, bromphenylbromide, and pentoxyfylline). Furthermore, ketoconazole attenuated X ray induced tumor necrosis factor gene expression. Conversely, indomethacin enhanced tumor necrosis factor expression following irradiation. The finding that radiation-induced tumor necrosis factor gene expression was attenuated by ketoconazole suggests that the lipoxygenase pathway participates in signal transduction preceding tumor necrosis factor induction. Enhancement of tumor necrosis factor expression by indomethacin following irradiation suggests that prostaglandins produced by cyclooxygenase act as negative regulators of tumor necrosis factor expression. Inhibitors of tumor necrosis factor induction ameliorate acute and subacute sequelae of radiotherapy. The authors propose therefore, that ketoconazole may reduce acute radiation sequelae such as mucositis and esophagitis through a reduction in tumor necrosis factor induction or inhibition of phospholipase A2 in addition to its antifungal activity. 25 refs., 2 figs.

Caffeine attenuates scopolamine-induced memory impairment in humans.

Science.gov (United States)

Riedel, W; Hogervorst, E; Leboux, R; Verhey, F; van Praag, H; Jolles, J

1995-11-01

Caffeine consumption can be beneficial for cognitive functioning. Although caffeine is widely recognized as a mild CNS stimulant drug, the most important consequence of its adenosine antagonism is cholinergic stimulation, which might lead to improvement of higher cognitive functions, particularly memory. In this study, the scopolamine model of amnesia was used to test the cholinergic effects of caffeine, administered as three cups of coffee. Subjects were 16 healthy volunteers who received 250 mg caffeine and 2 mg nicotine separately, in a placebo-controlled double-blind cross-over design. Compared to placebo, nicotine attenuated the scopolamine-induced impairment of storage in short-term memory and attenuated the scopolamine-induced slowing of speed of short-term memory scanning. Nicotine also attenuated the scopolamine-induced slowing of reaction time in a response competition task. Caffeine attenuated the scopolamine-induced impairment of free recall from short- and long-term memory, quality and speed of retrieval from long-term memory in a word learning task, and other cognitive and non-cognitive measures, such as perceptual sensitivity in visual search, reading speed, and rate of finger-tapping. On the basis of these results it was concluded that caffeine possesses cholinergic cognition enhancing properties. Caffeine could be used as a control drug in studies using the scopolamine paradigm and possibly also in other experimental studies of cognitive enhancers, as the effects of a newly developed cognition enhancing drug should at least be superior to the effects of three cups of coffee.

Evaluation of attenuating materials: model for the distribution of scattered radiation

International Nuclear Information System (INIS)

Costa, Paulo R.

1996-01-01

A mathematical model for the behaviour of the distribution of photon scattered by attenuating media is presented. Shielding barriers or attenuating materials used in tests of quality control in radiology are proposed. Comparative results for Lucite are reported

On the attenuation of x-rays and gamma-rays in dilute solutions

DEFF Research Database (Denmark)

Gerward, Leif

1996-01-01

The theory of X-ray and gamma-ray attenuation in solutions is developed. The rule of mixture for the calculation of mass and linear attenuation coefficients is elaborated in the general case as well as in the limit of extreme dilution. The validity of the latter approximation is illustrated...... by the attenuation of 17.443 keV X-rays in aqueous solutions of NaCl. Copyright (C) 1996 Elsevier Science Ltd...

MR-based attenuation correction for cardiac FDG PET on a hybrid PET/MRI scanner: comparison with standard CT attenuation correction

Energy Technology Data Exchange (ETDEWEB)

Vontobel, Jan; Liga, Riccardo; Possner, Mathias; Clerc, Olivier F.; Mikulicic, Fran; Veit-Haibach, Patrick; Voert, Edwin E.G.W. ter; Fuchs, Tobias A.; Stehli, Julia; Pazhenkottil, Aju P.; Benz, Dominik C.; Graeni, Christoph; Gaemperli, Oliver; Herzog, Bernhard; Buechel, Ronny R.; Kaufmann, Philipp A. [University Hospital Zurich, Department of Nuclear Medicine, Zurich (Switzerland)

2015-09-15

The aim of this study was to evaluate the feasibility of attenuation correction (AC) for cardiac {sup 18}F-labelled fluorodeoxyglucose (FDG) positron emission tomography (PET) using MR-based attenuation maps. We included 23 patients with no known cardiac history undergoing whole-body FDG PET/CT imaging for oncological indications on a PET/CT scanner using time-of-flight (TOF) and subsequent whole-body PET/MR imaging on an investigational hybrid PET/MRI scanner. Data sets from PET/MRI (with and without TOF) were reconstructed using MR AC and semi-quantitative segmental (20-segment model) myocardial tracer uptake (per cent of maximum) and compared to PET/CT which was reconstructed using CT AC and served as standard of reference. Excellent correlations were found for regional uptake values between PET/CT and PET/MRI with TOF (n = 460 segments in 23 patients; r = 0.913; p < 0.0001) with narrow Bland-Altman limits of agreement (-8.5 to +12.6 %). Correlation coefficients were slightly lower between PET/CT and PET/MRI without TOF (n = 460 segments in 23 patients; r = 0.851; p < 0.0001) with broader Bland-Altman limits of agreement (-12.5 to +15.0 %). PET/MRI with and without TOF showed minimal underestimation of tracer uptake (-2.08 and -1.29 %, respectively), compared to PET/CT. Relative myocardial FDG uptake obtained from MR-based attenuation corrected FDG PET is highly comparable to standard CT-based attenuation corrected FDG PET, suggesting interchangeability of both AC techniques. (orig.)

Relationship between comfort and attenuation measurements for two types of earplugs

Directory of Open Access Journals (Sweden)

David C Byrne

2011-01-01

Full Text Available Noise-induced hearing loss is almost always preventable if properly fitted hearing protectors are worn to reduce exposure. Many individuals choose not to wear hearing protection because it may interfere with effective communication in the workplace or it may be uncomfortable. Hearing protector comfort has not received the same amount of attention as noise reduction capability. The present study was conducted to evaluate the comfort level of two different types of insert earplugs as well as the attenuation levels achieved by the earplugs. Attenuation levels were obtained with a commercially available earplug fit-test system, and the comfort ratings were obtained by questionnaire. The primary research objective was to determine whether hearing protector comfort was related to measured attenuation values. A linear mixed effects model provided evidence for an inverse relationship between comfort and attenuation.

Attenuation maps for SPECT determined using cone beam transmission computed tomography

International Nuclear Information System (INIS)

Manglos, S.H.; Bassano, D.A.; Duxbury, C.E.; Capone, R.B.

1990-01-01

This paper presents a new method for measuring non-uniform attenuation maps, using a cone beam geometry CT scan acquired on a standard rotating gamma camera normally used for SPECT imaging. The resulting map is intended for use in non-uniform attenuation compensation of SPECT images. The method was implemented using a light-weight point source holder attached to the camera. A cone beam collimator may be used on the gamma camera, but the cone beam CT scans may also be acquired without collimator. In either implementation, the advantages include very high efficiency and resolution limited not by the collimator but by the intrinsic camera resolution (about 4 mm). Several phantoms tested the spatial uniformity, noise, linearity as a function of attenuation coefficient, and spatial resolution. Good quality attenuation maps were obtained, at least for the central slices where no truncation was present

Design guidelines for flexural wave attenuation of slender beams with local resonators

International Nuclear Information System (INIS)

Liu, Yaozong; Yu, Dianlong; Li, Li; Zhao, Honggang; Wen, Jihong; Wen, Xisen

2007-01-01

The complex band structures and attenuation spectra of flexural waves in slender beams with periodically mounted local resonators are investigated with transfer matrix method. It is noteworthy that the frequency range and attenuation coefficient of the locally resonant gap become larger in complex band structures if larger resonators were used. But given the total add-on mass of resonators, the attenuation spectra of finite beams with large but few resonators do not demonstrate such phenomena because the attenuation needs several periods to establish. So with the view of application, a large number of small local resonators widely spread along the beam are preferred given the total add-on mass to the beam

A Generalized Correction for Attenuation.

Science.gov (United States)

Petersen, Anne C.; Bock, R. Darrell

Use of the usual bivariate correction for attenuation with more than two variables presents two statistical problems. This pairwise method may produce a covariance matrix which is not at least positive semi-definite, and the bivariate procedure does not consider the possible influences of correlated errors among the variables. The method described…

Measurement of linear attenuation coefficient of different materials

International Nuclear Information System (INIS)

Ali, M. M.

2013-07-01

In this research we study the linear attenuation coefficient from the materials concrete, brick, mixture concrete and iron. In the secondary standard dosimetry laboratory in Atomic Energy from different distance by use Cs-137 sours, chamber farmer 2675 A-600 cc-S/N 0511, and electrometer 2670 A-S/N 114. Found the value of linear attenuation coefficient of concert in the range 0.167 cm -1 , the brick in the range 0.063 -1 and mixture concrete and iron in the range 0.253cm -1 .(Author)

Development of a human live attenuated West Nile infectious DNA vaccine: Identification of a minimal mutation set conferring the attenuation level acceptable for a human vaccine

Energy Technology Data Exchange (ETDEWEB)

Yamshchikov, Vladimir, E-mail: yaximik@gmail.com; Manuvakhova, Marina; Rodriguez, Efrain; Hébert, Charles

2017-01-15

ABSTRACT: For the development of a human West Nile (WN) infectious DNA (iDNA) vaccine, we created highly attenuated chimeric virus W1806 with the serological identity of highly virulent WN-NY99. Earlier, we attempted to utilize mutations found in the E protein of the SA14-14-2 vaccine to bring safety of W1806 to the level acceptable for human use (). Here, we analyzed effects of the SA14-14-2 changes on growth properties and neurovirulence of W1806. A set including the E138K, K279M, K439R and G447D changes was identified as the perspective subset for satisfying the target safety profile without compromising immunogenicity of the vaccine candidate. The genetic stability of the attenuated phenotype was found to be unsatisfactory being dependent on a subset of attenuating changes incorporated in W1806. Elucidation of underlying mechanisms influencing selection of pathways for restoration of the envelope protein functionality will facilitate resolution of the emerged genetic stability issue. - Highlights: •Effect of mutations in E on properties of WN1806 is determined. •A subset of attenuating mutations suitable for a human vaccine is defined. •Mechanism of attenuation is proposed and illustrated. •Underlying mechanisms of neurovirulence reversion are suggested.

Subsurface Contaminant Focus Area: Monitored Natural Attenuation (MNA)--Programmatic, Technical, and Regulatory Issues

Energy Technology Data Exchange (ETDEWEB)

Krupka, Kenneth M.; Martin, Wayne J.

2001-07-23

Natural attenuation processes are commonly used for remediation of contaminated sites. A variety of natural processes occur without human intervention at all sites to varying rates and degrees of effectiveness to attenuate (decrease) the mass, toxicity, mobility, volume, or concentration of organic and inorganic contaminants in soil, groundwater, and surface water systems. The objective of this review is to identify potential technical investments to be incorporated in the Subsurface Contaminant Focus Area Strategic Plan for monitored natural attenuation. When implemented, the technical investments will help evaluate and implement monitored natural attenuation as a remediation option at DOE sites. The outcome of this review is a set of conclusions and general recommendations regarding research needs, programmatic guidance, and stakeholder issues pertaining to monitored natural attenuation for the DOE complex.

Ultrasonic attenuation in niobium II: measurements near Bsub(c2)

International Nuclear Information System (INIS)

Forgan, E.M.; Gough, C.E.

1978-01-01

The attenuation of 10 to 90 MHz longitudinal sound waves has been measured from 1.2 K upwards in the superconducting mixed state of niobium near Bsub(c2). The attenuation was determined as a function of the directly measured average induction, B, within single crystal specimens which had resistance ratios ranging from 83 to 3380. The specimens tended to the 'clean' limit (electron mean free path, 1 much greater than xi 0 , the superconducting coherence length) in which there is a strong purity dependence of the relative attenuation. For the purest crystals close to Bsub(C2), the results are in reasonable agreement with the purity and field dependence predicted by microscopic theories, and agree over a much wider field range with a phenomenological modification of these theories. Measurements of attenuation and other transport properties in clean type II superconductors by other authors are discussed and it is shown that many of the evident discrepancies can be attributed to neglect of the effects of magnetic irreversibility and crystalline anisotropy. (author)

The frequency attenuation effect in identity and associative priming.

Science.gov (United States)

Nievas, Francisco

2010-05-01

Three lexical decision experiments were carried out, where the masked priming paradigm is used to study the role of the frequency attenuation effect (more priming in low-frequency target words than in high-frequency target words) in repetition and associative priming, manipulating Prime Duration (PD) and Stimulus Onset Asynchrony (SOA). A new concept was introduced, Minimum Time Threshold (MTT), this is, the minimum time interval of exposure to the masked word in order to become aware of it. Results support the notion that MTT is a key to the appearance of the frequency attenuation effect when enough word processing time is allowed. Results do not support the unified explanation of masked priming and long-term priming as proposed by Bodner and Masson (2001). Moreover, information feedback from the semantic level was not the reason for the frequency attenuation effect in repetition priming.

Attenuation of gamma radiation in concrete shields

International Nuclear Information System (INIS)

Azevedo e Souza, A.C. de.

1978-12-01

The attenuation characteristics of γ radiation in concrete layers considering their mechanical resistence and densities were determined. A 137 Cs source was used in a 'good geometry' arrangement to eliminate the effects of the buildup factor. The ordinary and the heavy concrete were irradiated and for the latter it was used as additives iron ore and Fe 2 O 3 pellets in various grain sizes. The detection system consisted of a 2' x 2' NaI (Tl) crystal coupled to a photomultiplier tube and the associated electronic equipment. FORTRAN programs were used for determining the absorption coefficients and the attenuation factors. These programs calculate photopeak areas eliminating all contributions due to Compton effect and background. (Author) [pt

Indoor signal attenuation assessment via fuzzy logic

Directory of Open Access Journals (Sweden)

Alexandre de Assis Mota

2011-09-01

Full Text Available This work focuses on the analysis of signal´s attenuation in indoor environments using a fuzzy logic approach based on the Shadowing Signal Propagation Model (SSPM. The SSPM allows the characterization of the attenuation caused by the environment through the ? parameter present in this model. In addition to this, the Fuzzy Logic provides a form of approximate reasoning that allows the treatment of problems with incomplete, vague and imprecise information. Also, it offers a simple way to obtain a possible solution for a problem using the heuristic knowledge about a particular situation. The results show that the methodology produced satisfactory results, close to the ones yielded by experimental methods.

Properties of sound attenuation around a two-dimensional underwater vehicle with a large cavitation number

International Nuclear Information System (INIS)

Ye Peng-Cheng; Pan Guang

2015-01-01

Due to the high speed of underwater vehicles, cavitation is generated inevitably along with the sound attenuation when the sound signal traverses through the cavity region around the underwater vehicle. The linear wave propagation is studied to obtain the influence of bubbly liquid on the acoustic wave propagation in the cavity region. The sound attenuation coefficient and the sound speed formula of the bubbly liquid are presented. Based on the sound attenuation coefficients with various vapor volume fractions, the attenuation of sound intensity is calculated under large cavitation number conditions. The result shows that the sound intensity attenuation is fairly small in a certain condition. Consequently, the intensity attenuation can be neglected in engineering. (paper)

Detailed study of seismic wave attenuation from four oilfields in Abu Dhabi, United Arab Emirates

Science.gov (United States)

Bouchaala, F.; Ali, M. Y.; Matsushima, J.

2018-02-01

In the present study, we provide a detailed study of seismic wave attenuation obtained from four oilfields. The reservoir zones of these oilfields are complicated due to complex fracture networks, the presence of tar mat and high heterogeneity of carbonate rocks of which the subsurface of Abu Dhabi is mainly composed. These complexities decrease signal-to-noise ratio and make attenuation estimation difficult. We obtained high-resolution attenuation profiles from vertical seismic profiling (VSP) and sonic waveform data. The VSP data were recorded in all four oilfields and the sonic data were acquired in the reservoir zones of oilfields I and IV. We found that the VSP scattering attenuation ({Q}{{S}{{c}}{{a}}{{t}}}-1) varies from -0.080 to 0.180 over a depth range of 400-3500 m. We attributed this significant scattering to the high heterogeneity of carbonate rocks. The scattering profiles seem to be sensitive to fractures, lithology heterogeneity and tar mat, but their effect is superimposed. The VSP intrinsic attenuation varies from -0.15 to 0.246 with high variation within each formation. Since intrinsic attenuation is closely related to fluids, we assumed that this variation is due to the non-uniform distribution of fluids caused by the complex porosity network of the subsurface. The sonic monopole attenuation ({Q}{{M}{{f}}}-1) in the reservoir zones ranges between 0.033-0.094 and dipole inline attenuation ({Q}{{I}{{n}}{{l}}}-1) ranges from 0.040-0.138. The sonic attenuation appears to be sensitive to the presence of fluid and type of fractures, where it shows high attenuation for open fractures and low attenuation for resistive fractures. The zones with high clay content display high sonic intrinsic attenuation in the reservoir of oilfield II. We explain this by the frictional movement between the clay and carbonates due to the elasticity contrast of these two materials. Therefore, the solid grain friction may be the dominant attenuation mechanism in those zones.

Mid-European seismic attenuation anomaly

Czech Academy of Sciences Publication Activity Database

Málek, Jiří; Brokešová, J.; Vackář, Jiří

2017-01-01

Roč. 712, AUG 21 (2017), s. 557-577 ISSN 0040-1951 Grant - others:AV ČR(CZ) StrategieAV21/4 Program:StrategieAV Institutional support: RVO:67985891 Keywords : seismic wave attenuation * peak ground motion * H/V ratio Subject RIV: DC - Siesmology, Volcanology, Earth Structure OBOR OECD: Geology Impact factor: 2.693, year: 2016

Measuring soil sydric content by the attenuation of a microwave signal

International Nuclear Information System (INIS)

Orden, S.; Goldberg, M.; Landini, A.; Sainato, C.; Bottini, L.; Arrigo, N.

1995-01-01

Measuring soil water content by means of microwave signal attenuation. The attenuation of microwave signal was used to measure the moisture of various soils. Samples of three soils with different textures and organic matter contents were used. The attenuation of the transmitted electromagnetic signal was measured for each sample with different values of soil moisture. Linear regression models were used to fit the experimental values obtained, and the 95% prediction interval was estimated for the attenuation. From the comparison between the moisture values obtained with this method and those of the gravimetric method, the advantages of the first one are seen, both in speed and in the possibility to estimate the in situ moisture, even if this method has a greater relative error. This method would be useful to operate an automatic control irrigation system, preventing hydric stress when the values of soil moisture reach near field capacity. (author) [es

Contaminant Attenuation and Transport Characterization of 200-UP-1 Operable Unit Sediment Samples

Energy Technology Data Exchange (ETDEWEB)

Lee, Brady D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Szecsody, James E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Qafoku, Nikolla [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); McElroy, Erin M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Baum, Steven R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Snyder, Michelle MV [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lawter, Amanda R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Resch, Charles T. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Gartman, Brandy N. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Zhong, Lirong [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Saunders, Danielle L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Williams, Benjamin D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Horner, Jacob A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Leavy, Ian I. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Christiansen, Beren B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Clayton, Ray E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Johnson, Kayla C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2017-09-27

Contaminants disposed of at the land surface migrate through the vadose zone, forming plumes in groundwater. Processes that occur in the groundwater can attenuate contaminant concentrations during transport through the aquifer. For this reason, quantifying contaminant attenuation and contaminant transport processes in the aquifer, in support of the conceptual site model (CSM) and fate and transport modeling, are important for assessing the need for, and type of, remediation in the groundwater, including monitored natural attenuation (MNA). The framework to characterize attenuation and transport processes provided in U.S. Environmental Protection Agency (EPA) guidance documents was used to guide the laboratory effort reported herein.

Intercomparison of medium-energy neutron attenuation in iron and concrete

International Nuclear Information System (INIS)

Hirayama, H.

1999-01-01

Neutron attenuation of medium energy below 1 GeV has not been well understood until now. It is desired to obtain common agreements concerning the behaviours of neutrons inside various materials. This is necessary in order to agree on definitions of the attenuation length, which is very important for shielding calculations involving high energy accelerators. As one attempt, it was proposed by Japanese attendants of SATIF-2 to compare the attenuation of medium-energy neutrons inside iron and concrete shields between various computer codes and data, and was cited as a suitable action for SATIF. The first results from three groups were presented at SATIF-3. It has become clear that neutrons above 20 MeV are important for understanding the attenuation inside materials and that the geometry, planar or spherical, does not affect the results very much. Considering the CPU times required for Monte Carlo calculations and this result, revised problems to be calculated were prepared by the Japanese Working Group and sent to the participants of this action. The geometry is only plane, and calculations are required only for neutrons above 20 MeV. The secondary neutrons from high energy protons, which were calculated by H. Nakashima, are also included in the problem. The results from four groups were sent to the organizer at the end of August. This paper presents a comparison between groups concerning the attenuation length together with the neutron spectrum and the future themes which come from this intercomparison. (author)

Attenuation and Velocity Structure in Spain and Morocco: Distinguishing Between Water, Temperature, and Partial Melt

Science.gov (United States)

Bezada, M. J.; Humphreys, E.

2014-12-01

Temperature, melt fraction, and water content affect seismic velocity and attenuation differently. Both are sensitive to temperature, but velocity is more sensitive to melt fraction and attenuation is thought to be more sensitive to water content. For these reasons, combining attenuation measurements with tomographic imaging of velocity structure can help untangle these fields and better resolve lithospheric structure and physical state. We map variations in attenuation beneath Spain and northern Morocco using teleseismic data generated by more than a dozen teleseismic deep-focus earthquakes recorded on a dense array of stations. For each event, we first estimate the source from the best quality recordings. We then apply an attenuation operator to the source estimate, using a range of t* values, to match the record at each station. We invert for a smooth map of t* from the ensemble of measurements. The spatial patterns in t* correlate very well with the tectonic domains in Spain and Morocco. In particular, areas in Spain that resisted deformation during the Variscan and Alpine orogenies produce very little attenuation. Comparing the attenuation map with seismic velocity structure we find that, in Morocco, some areas with strong low-velocity anomalies and recent volcanism do not cause high attenuation. These observations suggest that water content is a more likely cause for seismic attenuation in the study area than temperature, and that the non-attenuative low-velocity anomalies in Morocco are produced by partial mel.

Monitored Natural Attenuation of ino9rganic Contaminants Treatability Study Final Report

Energy Technology Data Exchange (ETDEWEB)

Crapse, K

2004-05-19

The identification and quantification of key natural attenuation processes for inorganic contaminants at D-Area is detailed herein. Two overarching goals of this evaluation of monitored natural attenuation (MNA) as a remediation strategy were (1) to better define the availability of inorganic contaminants as potential sources for transport to groundwater and uptake by environmental receptors and (2) to understand the site-specific mechanisms controlling attenuation of these inorganic contaminants through tandem geochemical and biological characterization. Data collected in this study provides input for more appropriate site groundwater transport models. Significant natural attenuation is occurring at D-Area as evidenced by relatively low aqueous concentrations of constituents of concern (COCs) (Be, Ni, U, and As) at all locations characterized and the decrease in groundwater concentrations with increasing distance from the source. The observed magnitude of decrease in groundwater concentrations of COCs with distance from the D-Area Coal Pile Runoff Basin (DCPRB) could not be accounted for by the modeled physical attenuation processes of dilution/dispersion. This additional attenuation, i.e., the observed difference between the groundwater concentrations of COCs and the modeled physical attenuation, is due to biogeochemical processes occurring at the D-Area. In tandem geochemical and microbiological characterization studies designed to evaluate the mechanisms contributing to natural attenuation, pH was the single parameter found to be most predictive of contaminant attenuation. The increasing pH with distance from the source is likely responsible for increased sorption of COCs to soil surfaces within the aquifer at D-Area. Importantly, because the sediments appear to have a high buffering capacity, the acid emanating from the DCPRB has been neutralized by the soil, and these conditions have led to large Kd values at the site. Two major types of soils are present at

Improvements to the Chebyshev expansion of attenuation correction factors for cylindrical samples

International Nuclear Information System (INIS)

Mildner, D.F.R.; Carpenter, J.M.

1990-01-01

The accuracy of the Chebyshev expansion coefficients used for the calculation of attenuation correction factors for cylinderical samples has been improved. An increased order of expansion allows the method to be useful over a greater range of attenuation. It is shown that many of these coefficients are exactly zero, others are rational numbers, and others are rational frations of π -1 . The assumptions of Sears in his asymptotic expression of the attenuation correction factor are also examined. (orig.)

Mapping of the mutations present in the genome of the Rift Valley fever virus attenuated MP12 strain and their putative role in attenuation.

Science.gov (United States)

Vialat, P; Muller, R; Vu, T H; Prehaud, C; Bouloy, M

1997-11-01

The MP12 attenuated strain of Rift Valley fever virus was obtained by 12 serial passages of a virulent isolate ZH548 in the presence of 5-fluorouracil (Caplen et al., 1985. Mutagen-directed attenuation of Rift Valley fever virus as a method for vaccine development. J. Gen. Virol., 66, 2271-2277). The comparison of the M segment of the two strains has already been reported by Takehara et al. (Takehara et al., 1989. Identification of mutations in the M RNA of a candidate vaccine strain of Rift Valley fever virus. Virology 169, 452-457). We have completed the comparison and found that altogether a total of nine, 12 and four nucleotides were changed in the L, M and S segments of the two strains, respectively. Three mutations induced amino acid changes in the L protein but none of them was located in the recognized motifs conserved among RNA dependent polymerases. In the S segment, a single change modified an amino acid in the NSs protein and in the M segment, seven of the mutations resulted in amino acid changes in each of the four encoded G1, G2, 14 kDa and 78 kDa proteins. Characterization of the MP12 virus indicated that determinants for attenuation were present in each segment and that they were introduced progressively during the 12 passages in the presence of the mutagen (Saluzzo and Smith, 1990. Use of reassortant viruses to map attenuating and temperature-sensitive mutations of the Rift Valley fever virus MP-12 vaccine. Vaccine 8, 369-375). Passages 4 and 7-9 were found to be essential for introduction of temperature-sensitive lesions and attenuation. In an attempt to correlate some of the mutations with the attenuated or temperature-sensitive phenotypes, we determined by sequencing the passage level at which the different mutations appeared. This work should help to address the question of the role of the viral gene products in Rift Valley fever pathogenesis.

Flexural wave attenuation in a sandwich beam with viscoelastic periodic cores

Science.gov (United States)

Guo, Zhiwei; Sheng, Meiping; Pan, Jie

2017-07-01

The flexural-wave attenuation performance of traditional constraint-layer damping in a sandwich beam is improved by using periodic constrained-layer damping (PCLD), where the monolithic viscoelastic core is replaced with two periodically alternating viscoelastic cores. Closed-form solutions of the wave propagation constants of the infinite periodic sandwich beam and the forced response of the corresponding finite sandwich structure are theoretically derived, providing computational support on the analysis of attenuation characteristics. In a sandwich beam with PCLD, the flexural waves can be attenuated by both Bragg scattering effect and damping effect, where the attenuation level is mainly dominated by Bragg scattering in the band-gaps and by damping in the pass-bands. Affected by these two effects, when the parameters of periodic cores are properly selected, a sandwich beam with PCLD can effectively reduce vibrations of much lower frequencies than that with traditional constrained-layer damping. The effects of the parameters of viscoelastic periodic cores on band-gap properties are also discussed, showing that the average attenuation in the desired frequency band can be maximized by tuning the length ratio and core thickness to proper values. The research in this paper could possibly provide useful information for the researches and engineers to design damping structures.

Evaluation of dose attenuation factor of armored car against radiation accidents

International Nuclear Information System (INIS)

Sato, Tatsuhiko; Fujii, Katsutoshi; Murayama, Takashi

2002-03-01

The Tokyo Fire Department developed an armored car against radiation accidents. The car is covered by lead shields for attenuating dose from gamma rays. Dose from neutrons also can be attenuated by pouring water into tanks attached to the surface of the car. However, dose attenuation factors of the radiation shields had been determined by an estimation of single-layer shield, and more precise evaluation of multi-layer shield was required. By request from the Tokyo Fire Department, a precise evaluation of the dose attenuation in multi-layer shield was carried out. The evaluation was made by a Monte Carlo radiation transport simulation code MCNP4B for the shields used in the front, side and back of the car. Three types of the radiation sources ( 252 Cf as a neutron source, 60 Co as a gamma ray source, and radiation source corresponding to the JCO criticality accident) were considered in the calculation. Benchmark experiments using neutron and gamma ray sources were also performed for ensuring the evaluation method. As a result, it was found out that doses of neutron and gamma ray were attenuated to approximately 10% and 25% by the thickest shield, respectively. These values were close to the ones which had already obtained by the estimation of single-layer shield. (author)

Prediction of Near-Field Wave Attenuation Due to a Spherical Blast Source

Science.gov (United States)

Ahn, Jae-Kwang; Park, Duhee

2017-11-01

Empirical and theoretical far-field attenuation relationships, which do not capture the near-field response, are most often used to predict the peak amplitude of blast wave. Jiang et al. (Vibration due to a buried explosive source. PhD Thesis, Curtin University, Western Australian School of Mines, 1993) present rigorous wave equations that simulates the near-field attenuation to a spherical blast source in damped and undamped media. However, the effect of loading frequency and velocity of the media have not yet been investigated. We perform a suite of axisymmetric, dynamic finite difference analyses to simulate the propagation of stress waves induced by spherical blast source and to quantify the near-field attenuation. A broad range of loading frequencies, wave velocities, and damping ratios are used in the simulations. The near-field effect is revealed to be proportional to the rise time of the impulse load and wave velocity. We propose an empirical additive function to the theoretical far-field attenuation curve to predict the near-field range and attenuation. The proposed curve is validated against measurements recorded in a test blast.

Inhomogeneity of neutron and gamma-ray attenuation in biological shields

Energy Technology Data Exchange (ETDEWEB)

El-bakkoush, F A; El-Ghobary, A M; Megahid, R M [Reactor and Neutron physics Department, Nuclear Research Center, A.E.A., Cairo (Egypt)

1997-12-31

Measurements have been carried-out to investigate the attenuation properties of some materials which are used as biological shields around nuclear radiation sources. Investigation was performed by measuring the transmitted fast neutron and gamma-spectra through cylindrical samples of magnetite- limonite, steel and cellulose shields. The neutron and gamma spectra were measured by a neutron-gamma spectrometer with stilbene scintillator. Discrimination between neutron and gamma pulses was achieved by a discrimination method. The obtained results are displayed in the form of neutron and gamma spectra and attenuation relations which are used to derive the total macroscopic cross-sections for neutrons and total linear attenuation coefficients for gamma-rays. The values of neutron and gamma relaxation lengths are also derived for the investigated materials. 10 figs., 1 tabs.

Determination of intrinsic attenuation in the oceanic lithosphere-asthenosphere system

Science.gov (United States)

Takeuchi, Nozomu; Kawakatsu, Hitoshi; Shiobara, Hajime; Isse, Takehi; Sugioka, Hiroko; Ito, Aki; Utada, Hisashi

2017-12-01

We recorded P and S waves traveling through the oceanic lithosphere-asthenosphere system (LAS) using broadband ocean-bottom seismometers in the northwest Pacific, and we quantitatively separated the intrinsic (anelastic) and extrinsic (scattering) attenuation effects on seismic wave propagation to directly infer the thermomechanical properties of the oceanic LAS. The strong intrinsic attenuation in the asthenosphere obtained at higher frequency (~3 hertz) is comparable to that constrained at lower frequency (~100 seconds) by surface waves and suggests frequency-independent anelasticity, whereas the intrinsic attenuation in the lithosphere is frequency dependent. This difference in frequency dependence indicates that the strong and broad peak dissipation recently observed in the laboratory exists only in the asthenosphere and provides new insight into what distinguishes the asthenosphere from the lithosphere.

Anomalous ultrasonic attenuation and velocity change in LaAl2

International Nuclear Information System (INIS)

Federle, G.; Dransfeld, K.; Boemmel, H.E.; Roedhammer, P.

1980-01-01

The attenuation and velocity of longitudinal waves has been measured in superconducting and normal LaAl 2 in the frequency range from 15 to 225 MHz. Both in the superconducting and in the normal state an unusually large damping has been found superimposed on the relatively small attenuation due to the well known electron-phonon interaction. On cooling into the superconducting state the attenuation starts to drop only at temperatures well below Tsub(c) and - as in insulating glasses - it rises again below 0.8K. It is suggested that this indicates that two-level systems similar to the ones found in amorphous superconductors may be present in the crystalline LaAl 2 sample and are responsible for the observed acoustic anomalies. (author)

Restorative effect of endurance exercise on behavioral deficits in the chronic mouse model of Parkinson's disease with severe neurodegeneration

Science.gov (United States)

Pothakos, Konstantinos; Kurz, Max J; Lau, Yuen-Sum

2009-01-01

Background Animal models of Parkinson's disease have been widely used for investigating the mechanisms of neurodegenerative process and for discovering alternative strategies for treating the disease. Following 10 injections with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 25 mg/kg) and probenecid (250 mg/kg) over 5 weeks in mice, we have established and characterized a chronic mouse model of Parkinson's disease (MPD), which displays severe long-term neurological and pathological defects resembling that of the human Parkinson's disease in the advanced stage. The behavioral manifestations in this chronic mouse model of Parkinson's syndrome remain uninvestigated. The health benefit of exercise in aging and in neurodegenerative disorders including the Parkinson's disease has been implicated; however, clinical and laboratory studies in this area are limited. In this research with the chronic MPD, we first conducted a series of behavioral tests and then investigated the impact of endurance exercise on the identified Parkinsonian behavioral deficits. Results We report here that the severe chronic MPD mice showed significant deficits in their gait pattern consistency and in learning the cued version of the Morris water maze. Their performances on the challenging beam and walking grid were considerably attenuated suggesting the lack of balance and motor coordination. Furthermore, their spontaneous and amphetamine-stimulated locomotor activities in the open field were significantly suppressed. The behavioral deficits in the chronic MPD lasted for at least 8 weeks after MPTP/probenecid treatment. When the chronic MPD mice were exercise-trained on a motorized treadmill 1 week before, 5 weeks during, and 8–12 weeks after MPTP/probenecid treatment, the behavioral deficits in gait pattern, spontaneous ambulatory movement, and balance performance were reversed; whereas neuronal loss and impairment in cognitive skill, motor coordination, and amphetamine

Restorative effect of endurance exercise on behavioral deficits in the chronic mouse model of Parkinson's disease with severe neurodegeneration

Directory of Open Access Journals (Sweden)

Lau Yuen-Sum

2009-01-01

Full Text Available Abstract Background Animal models of Parkinson's disease have been widely used for investigating the mechanisms of neurodegenerative process and for discovering alternative strategies for treating the disease. Following 10 injections with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 25 mg/kg and probenecid (250 mg/kg over 5 weeks in mice, we have established and characterized a chronic mouse model of Parkinson's disease (MPD, which displays severe long-term neurological and pathological defects resembling that of the human Parkinson's disease in the advanced stage. The behavioral manifestations in this chronic mouse model of Parkinson's syndrome remain uninvestigated. The health benefit of exercise in aging and in neurodegenerative disorders including the Parkinson's disease has been implicated; however, clinical and laboratory studies in this area are limited. In this research with the chronic MPD, we first conducted a series of behavioral tests and then investigated the impact of endurance exercise on the identified Parkinsonian behavioral deficits. Results We report here that the severe chronic MPD mice showed significant deficits in their gait pattern consistency and in learning the cued version of the Morris water maze. Their performances on the challenging beam and walking grid were considerably attenuated suggesting the lack of balance and motor coordination. Furthermore, their spontaneous and amphetamine-stimulated locomotor activities in the open field were significantly suppressed. The behavioral deficits in the chronic MPD lasted for at least 8 weeks after MPTP/probenecid treatment. When the chronic MPD mice were exercise-trained on a motorized treadmill 1 week before, 5 weeks during, and 8–12 weeks after MPTP/probenecid treatment, the behavioral deficits in gait pattern, spontaneous ambulatory movement, and balance performance were reversed; whereas neuronal loss and impairment in cognitive skill, motor coordination, and

Ultrasonic attenuation in rare-earth monoarsenides

Indian Academy of Sciences (India)

2015-11-27

Home; Journals; Pramana – Journal of Physics; Volume 86; Issue 6. Ultrasonic attenuation in rare-earth monoarsenides .... Proceedings of the International Workshop/Conference on Computational Condensed Matter Physics and Materials Science (IWCCMP-2015). Posted on November 27, 2015. Guest Editors: Anurag ...

Protective actions of the vesicular monoamine transporter 2 (VMAT2) in monoaminergic neurons.

Science.gov (United States)

Guillot, Thomas S; Miller, Gary W

2009-04-01

Vesicular monoamine transporters (VMATs) are responsible for the packaging of neurotransmitters such as dopamine, serotonin, norepinephrine, and epinephrine into synaptic vesicles. These proteins evolved from precursors in the major facilitator superfamily of transporters and are among the members of the toxin extruding antiporter family. While the primary function of VMATs is to sequester neurotransmitters within vesicles, they can also translocate toxicants away from cytosolic sites of action. In the case of dopamine, this dual role of VMAT2 is combined-dopamine is more readily oxidized in the cytosol where it can cause oxidative stress so packaging into vesicles serves two purposes: neurotransmission and neuroprotection. Furthermore, the deleterious effects of exogenous toxicants on dopamine neurons, such as MPTP, can be attenuated by VMAT2 activity. The active metabolite of MPTP can be kept within vesicles and prevented from disrupting mitochondrial function thereby sparing the dopamine neuron. The highly addictive drug methamphetamine is also neurotoxic to dopamine neurons by using dopamine itself to destroy the axon terminals. Methamphetamine interferes with vesicular sequestration and increases the production of dopamine, escalating the amount in the cytosol and leading to oxidative damage of terminal components. Vesicular transport seems to resist this process by sequestering much of the excess dopamine, which is illustrated by the enhanced methamphetamine neurotoxicity in VMAT2-deficient mice. It is increasingly evident that VMAT2 provides neuroprotection from both endogenous and exogenous toxicants and that while VMAT2 has been adapted by eukaryotes for synaptic transmission, it is derived from phylogenetically ancient proteins that originally evolved for the purpose of cellular protection.

Note: Attenuation motion of acoustically levitated spherical rotor

Science.gov (United States)

Lü, P.; Hong, Z. Y.; Yin, J. F.; Yan, N.; Zhai, W.; Wang, H. P.

2016-11-01

Here we observe the attenuation motion of spherical rotors levitated by near-field acoustic radiation force and analyze the factors that affect the duration time of free rotation. It is found that the rotating speed of freely rotating rotor decreases exponentially with respect to time. The time constant of exponential attenuation motion depends mainly on the levitation height, the mass of rotor, and the depth of concave ultrasound emitter. Large levitation height, large mass of rotor, and small depth of concave emitter are beneficial to increase the time constant and hence extend the duration time of free rotation.

Attenuation compensation for least-squares reverse time migration using the viscoacoustic-wave equation

KAUST Repository

Dutta, Gaurav

2014-10-01

Strong subsurface attenuation leads to distortion of amplitudes and phases of seismic waves propagating inside the earth. Conventional acoustic reverse time migration (RTM) and least-squares reverse time migration (LSRTM) do not account for this distortion, which can lead to defocusing of migration images in highly attenuative geologic environments. To correct for this distortion, we used a linearized inversion method, denoted as Qp-LSRTM. During the leastsquares iterations, we used a linearized viscoacoustic modeling operator for forward modeling. The adjoint equations were derived using the adjoint-state method for back propagating the residual wavefields. The merit of this approach compared with conventional RTM and LSRTM was that Qp-LSRTM compensated for the amplitude loss due to attenuation and could produce images with better balanced amplitudes and more resolution below highly attenuative layers. Numerical tests on synthetic and field data illustrated the advantages of Qp-LSRTM over RTM and LSRTM when the recorded data had strong attenuation effects. Similar to standard LSRTM, the sensitivity tests for background velocity and Qp errors revealed that the liability of this method is the requirement for smooth and accurate migration velocity and attenuation models.

Attenuation compensation for least-squares reverse time migration using the viscoacoustic-wave equation

KAUST Repository

Dutta, Gaurav; Schuster, Gerard T.

2014-01-01

Strong subsurface attenuation leads to distortion of amplitudes and phases of seismic waves propagating inside the earth. Conventional acoustic reverse time migration (RTM) and least-squares reverse time migration (LSRTM) do not account for this distortion, which can lead to defocusing of migration images in highly attenuative geologic environments. To correct for this distortion, we used a linearized inversion method, denoted as Qp-LSRTM. During the leastsquares iterations, we used a linearized viscoacoustic modeling operator for forward modeling. The adjoint equations were derived using the adjoint-state method for back propagating the residual wavefields. The merit of this approach compared with conventional RTM and LSRTM was that Qp-LSRTM compensated for the amplitude loss due to attenuation and could produce images with better balanced amplitudes and more resolution below highly attenuative layers. Numerical tests on synthetic and field data illustrated the advantages of Qp-LSRTM over RTM and LSRTM when the recorded data had strong attenuation effects. Similar to standard LSRTM, the sensitivity tests for background velocity and Qp errors revealed that the liability of this method is the requirement for smooth and accurate migration velocity and attenuation models.

Iterative reconstruction with attenuation compensation from cone-beam projections acquired via nonplanar orbits

International Nuclear Information System (INIS)

Zeng, G.L.; Weng, Y.; Gullberg, G.T.

1997-01-01

Single photon emission computed tomography (SPECT) imaging with cone-beam collimators provides improved sensitivity and spatial resolution for imaging small objects with large field-of-view detectors. It is known that Tuy's cone-beam data sufficiency condition must be met to obtain artifact-free reconstructions. Even though Tuy's condition was derived for an attenuation-free situation, the authors hypothesize that an artifact-free reconstruction can be obtained even if the cone-beam data are attenuated, provided the imaging orbit satisfies Tuy's condition and the exact attenuation map is known. In the authors' studies, emission data are acquired using nonplanar circle-and-line orbits to acquire cone-beam data for tomographic reconstructions. An extended iterative ML-EM (maximum likelihood-expectation maximization) reconstruction algorithm is derived and used to reconstruct projection data with either a pre-acquired or assumed attenuation map. Quantitative accuracy of the attenuation corrected emission reconstruction is significantly improved

Weighted backprojection implemented with a non-uniform attenuation map for improved SPECT quantitation

International Nuclear Information System (INIS)

Manglos, S.H.; Jaszczak, R.J.; Floyd, C.E.

1988-01-01

A method is developed to improve quantitation in SPECT imaging by using an attenuation compensation method which includes the correct non-uniform attenuation spatial distribution (''map''). The method is based on the technique of weighted back projection, previously developed for uniform attenuation. The method is tested by imaging a non-uniform phantom, reconstructing with the known attenuation map, and quantitatively comparing the resultant image with the known activity distribution. Reconstructed image profiles are dramatically improved in comparison to reconstructions without compensation or with an assumed uniform attenuation map. Contrast measurements further quantify the improvement. Line spread function distortions seen previously in non-uniform geometries are essentially eliminated by the method. Therefore, the method appears to be appropriate for these geometries, if the non-uniform map can be determined. Some additional image distortions introduced by the compensation method are noted and will require further study

Active acoustic leak detection for LMFBR steam generator. Sound attenuation due to bubbles

International Nuclear Information System (INIS)

Kumagai, Hiromichi; Sakuma, Toshio

1995-01-01

In the steam generators (SG) of LMFBR, it is necessary to detect the leakage of water from tubes of heat exchangers as soon as it occurs. The active acoustic detection method has drawn general interest owing to its short response time and reduction of the influence of background noise. In this paper, the application of the active acoustic detection method for SG is proposed, and sound attenuation by bubbles is investigated experimentally. Furthermore, using the SG sector model, sound field characteristics and sound attenuation characteristics due to injection of bubbles are studied. It is clarified that the sound attenuation depends upon bubble size as well as void fraction, that the distance attenuation of sound in the SG model containing heat transfer tubes is 6dB for each two-fold increase of distance, and that emitted sound attenuates immediately upon injection of bubbles. (author)

Millimetre wave attenuation of prototype diagnostic components for the ITER bolometers

Energy Technology Data Exchange (ETDEWEB)

Meister, H., E-mail: meister@ipp.mpg.de [Max-Planck-Institut für Plasmaphysik, Garching (Germany); Kasparek, W. [Universität Stuttgart, Institut für Grenzflächenverfahrenstechnik & Plasmatechnologie, Stuttgart (Germany); Zhang, D.; Hirsch, M. [Max-Planck-Institut für Plasmaphysik, Teilinstitut Greifswald, Greifswald (Germany); Koll, J. [Max-Planck-Institut für Plasmaphysik, Garching (Germany); Zeitler, A. [Universität Stuttgart, Institut für Grenzflächenverfahrenstechnik & Plasmatechnologie, Stuttgart (Germany)

2015-10-15

Highlights: • Attenuation of ECRH stray radiation in ITER demonstrated for bolometer prototypes. • Collimator with microwave reflecting grid achieves >70 dB at 170 GHz (ITER frequency). • For frequencies >250 GHz (ECE radiation) ceramic coating showed 40 dB attenuation. • Good shielding at joints of components is prerequisite to prevent microwave leakage. • These methods prevent the impact of ECRH stray radiation on bolometer measurements. - Abstract: Bolometers in current and future fusion devices, in particular those in ITER, are vulnerable to stray radiation from electron cyclotron resonance heating (ECRH) which results in measurement errors for plasma radiation detection. To protect the detectors from this stray radiation in the millimetre wavelength range, dedicated diagnostic components have been designed and tested. One option is to place a top plate which contains a microwave-reflecting grid onto the collimators. Another option investigated is the coating of the collimator channels using a microwave absorbing ceramic. Measurements of the mm-wave attenuation of the collimator in front of the bolometer detectors with and without top plate or coated collimator channels have been performed in the frequency range of 125–420 GHz. The attenuation factor of the collimator channels at 170 GHz (the ECRH frequency for ITER) with neither microwave grid nor coating is typically 10 dB. The coating enhances this to 40 dB and including the microwave grid yields at least an attenuation factor of 70 dB, which is sufficient to reduce the residual ECRH induced signal significantly below the one due to plasma radiation. Placing a bolometer camera (collimator connected to detector housing) inside the isotropic microwave field of the test facility MISTRAL, the attenuation factor of the full diagnostic set-up using a top plate was determined to be in the order of 45 dB. This degraded attenuation implies that particular attention has to be paid to design and quality

Interpersonal sensitivity and persistent attenuated psychotic symptoms in adolescence.

Science.gov (United States)

Masillo, Alice; Brandizzi, M; Valmaggia, L R; Saba, R; Lo Cascio, N; Lindau, J F; Telesforo, L; Venturini, P; Montanaro, D; Di Pietro, D; D'Alema, M; Girardi, P; Fiori Nastro, P

2018-03-01

Interpersonal sensitivity defines feelings of inner-fragility in the presence of others due to the expectation of criticism or rejection. Interpersonal sensitivity was found to be related to attenuated positive psychotic symptom during the prodromal phase of psychosis. The aims of this study were to examine if high level of interpersonal sensitivity at baseline are associated with the persistence of attenuated positive psychotic symptoms and general psychopathology at 18-month follow-up. A sample of 85 help-seeking individuals (mean age = 16.6, SD = 5.05) referred an Italian early detection project, completed the interpersonal sensitivity measure and the structured interview for prodromal symptoms (SIPS) at baseline and were assessed at 18-month follow-up using the SIPS. Results showed that individuals with high level of interpersonal sensitivity at baseline reported high level of attenuated positive psychotic symptoms (i.e., unusual thought content) and general symptoms (i.e., depression, irritability and low tolerance to daily stress) at follow-up. This study suggests that being "hypersensitive" to interpersonal interactions is a psychological feature associated with attenuated positive psychotic symptoms and general symptoms, such as depression and irritability, at 18-month follow-up. Assessing and treating inner-self fragilities may be an important step of early detection program to avoid the persistence of subtle but very distressing long-terms symptoms.

MR constrained simultaneous reconstruction of activity and attenuation maps in brain TOF-PET/MR imaging

Energy Technology Data Exchange (ETDEWEB)

Mehranian, Abolfazl; Zaidi, Habib [Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1211 Geneva (Switzerland)

2014-07-29

The maximum likelihood estimation of attenuation and activity (MLAA) algorithm has been proposed to jointly estimate activity and attenuation from emission data only. Salomon et al employed the MLAA to estimate activity and attenuation from time-of-flight PET data with spatial MR prior information on attenuation. Recently, we proposed a novel algorithm to impose both spatial and statistical constraints on attenuation estimation within the MLAA algorithm using Dixon MR images and a constrained Gaussian mixture model (GMM). In this study, we compare the proposed algorithm with MLAA and MLAA-Salomon in brain TOF-PET/MR imaging.

MR constrained simultaneous reconstruction of activity and attenuation maps in brain TOF-PET/MR imaging

International Nuclear Information System (INIS)

Mehranian, Abolfazl; Zaidi, Habib

2014-01-01

The maximum likelihood estimation of attenuation and activity (MLAA) algorithm has been proposed to jointly estimate activity and attenuation from emission data only. Salomon et al employed the MLAA to estimate activity and attenuation from time-of-flight PET data with spatial MR prior information on attenuation. Recently, we proposed a novel algorithm to impose both spatial and statistical constraints on attenuation estimation within the MLAA algorithm using Dixon MR images and a constrained Gaussian mixture model (GMM). In this study, we compare the proposed algorithm with MLAA and MLAA_Salomon in brain TOF-PET/MR imaging.

Inferring global upper-mantle shear attenuation structure by waveform tomography using the spectral element method

Science.gov (United States)

Karaoǧlu, Haydar; Romanowicz, Barbara

2018-06-01

We present a global upper-mantle shear wave attenuation model that is built through a hybrid full-waveform inversion algorithm applied to long-period waveforms, using the spectral element method for wavefield computations. Our inversion strategy is based on an iterative approach that involves the inversion for successive updates in the attenuation parameter (δ Q^{-1}_μ) and elastic parameters (isotropic velocity VS, and radial anisotropy parameter ξ) through a Gauss-Newton-type optimization scheme that employs envelope- and waveform-type misfit functionals for the two steps, respectively. We also include source and receiver terms in the inversion steps for attenuation structure. We conducted a total of eight iterations (six for attenuation and two for elastic structure), and one inversion for updates to source parameters. The starting model included the elastic part of the relatively high-resolution 3-D whole mantle seismic velocity model, SEMUCB-WM1, which served to account for elastic focusing effects. The data set is a subset of the three-component surface waveform data set, filtered between 400 and 60 s, that contributed to the construction of the whole-mantle tomographic model SEMUCB-WM1. We applied strict selection criteria to this data set for the attenuation iteration steps, and investigated the effect of attenuation crustal structure on the retrieved mantle attenuation structure. While a constant 1-D Qμ model with a constant value of 165 throughout the upper mantle was used as starting model for attenuation inversion, we were able to recover, in depth extent and strength, the high-attenuation zone present in the depth range 80-200 km. The final 3-D model, SEMUCB-UMQ, shows strong correlation with tectonic features down to 200-250 km depth, with low attenuation beneath the cratons, stable parts of continents and regions of old oceanic crust, and high attenuation along mid-ocean ridges and backarcs. Below 250 km, we observe strong attenuation in the

Physical and biogeochemical controls on light attenuation in a eutrophic, back-barrier estuary

Science.gov (United States)

Ganju, Neil K.; Miselis, Jennifer L.; Aretxabaleta, Alfredo L.

2014-01-01

Light attenuation is a critical parameter governing the ecological function of shallow estuaries. In these systems primary production is often dominated by benthic macroalgae and seagrass; thus light penetration to the bed is of primary importance. We quantified light attenuation in three seagrass meadows in Barnegat Bay, New Jersey, a shallow eutrophic back-barrier estuary; two of the sites were located within designated Ecologically Sensitive Areas (ESAs). We sequentially deployed instrumentation measuring photosynthetically active radiation, chlorophyll-a (chl-a) fluorescence, dissolved organic matter fluorescence (fDOM; a proxy for colored DOM absorbance), turbidity, pressure, and water velocity at 10 min intervals over three week periods at each site. At the southernmost site, where sediment availability was highest, light attenuation was highest and dominated by turbidity and to a lesser extent chl-a and CDOM. At the central site, chl-a dominated followed by turbidity and CDOM, and at the northernmost site turbidity and CDOM contributed equally to light attenuation. At a given site, the temporal variability of light attenuation exceeded the difference in median light attenuation at the three sites, indicating the need for continuous high-temporal resolution measurements. Vessel wakes, anecdotally implicated in increasing sediment resuspension, did not contribute to local resuspension within the seagrass beds, though frequent vessel wakes were observed in the channels. With regards to light attenuation and water clarity, physical and biogeochemical variables appear to outweigh any regulation of boat traffic within the ESAs.

An ice-sheet-wide framework for englacial attenuation from ice-penetrating radar data

Science.gov (United States)

Jordan, T. M.; Bamber, J. L.; Williams, C. N.; Paden, J. D.; Siegert, M. J.; Huybrechts, P.; Gagliardini, O.; Gillet-Chaulet, F.

2016-07-01

Radar inference of the bulk properties of glacier beds, most notably identifying basal melting, is, in general, derived from the basal reflection coefficient. On the scale of an ice sheet, unambiguous determination of basal reflection is primarily limited by uncertainty in the englacial attenuation of the radio wave, which is an Arrhenius function of temperature. Existing bed-returned power algorithms for deriving attenuation assume that the attenuation rate is regionally constant, which is not feasible at an ice-sheet-wide scale. Here we introduce a new semi-empirical framework for deriving englacial attenuation, and, to demonstrate its efficacy, we apply it to the Greenland Ice Sheet. A central feature is the use of a prior Arrhenius temperature model to estimate the spatial variation in englacial attenuation as a first guess input for the radar algorithm. We demonstrate regions of solution convergence for two input temperature fields and for independently analysed field campaigns. The coverage achieved is a trade-off with uncertainty and we propose that the algorithm can be "tuned" for discrimination of basal melt (attenuation loss uncertainty ˜ 5 dB). This is supported by our physically realistic ( ˜ 20 dB) range for the basal reflection coefficient. Finally, we show that the attenuation solution can be used to predict the temperature bias of thermomechanical ice sheet models and is in agreement with known model temperature biases at the Dye 3 ice core.

Envelope exchange for the generation of live-attenuated arenavirus vaccines.

Directory of Open Access Journals (Sweden)

Andreas Bergthaler

2006-06-01

Full Text Available Arenaviruses such as Lassa fever virus cause significant mortality in endemic areas and represent potential bioterrorist weapons. The occurrence of arenaviral hemorrhagic fevers is largely confined to Third World countries with a limited medical infrastructure, and therefore live-attenuated vaccines have long been sought as a method of choice for prevention. Yet their rational design and engineering have been thwarted by technical limitations. In addition, viral genes had not been identified that are needed to cause disease but can be deleted or substituted to generate live-attenuated vaccine strains. Lymphocytic choriomeningitis virus, the prototype arenavirus, induces cell-mediated immunity against Lassa fever virus, but its safety for humans is unclear and untested. Using this virus model, we have developed the necessary methodology to efficiently modify arenavirus genomes and have exploited these techniques to identify an arenaviral Achilles' heel suitable for targeting in vaccine design. Reverse genetic exchange of the viral glycoprotein for foreign glycoproteins created attenuated vaccine strains that remained viable although unable to cause disease in infected mice. This phenotype remained stable even after extensive propagation in immunodeficient hosts. Nevertheless, the engineered viruses induced T cell-mediated immunity protecting against overwhelming systemic infection and severe liver disease upon wild-type virus challenge. Protection was established within 3 to 7 d after immunization and lasted for approximately 300 d. The identification of an arenaviral Achilles' heel demonstrates that the reverse genetic engineering of live-attenuated arenavirus vaccines is feasible. Moreover, our findings offer lymphocytic choriomeningitis virus or other arenaviruses expressing foreign glycoproteins as promising live-attenuated arenavirus vaccine candidates.

Envelope Exchange for the Generation of Live-Attenuated Arenavirus Vaccines.

Directory of Open Access Journals (Sweden)

2006-06-01

Full Text Available Arenaviruses such as Lassa fever virus cause significant mortality in endemic areas and represent potential bioterrorist weapons. The occurrence of arenaviral hemorrhagic fevers is largely confined to Third World countries with a limited medical infrastructure, and therefore live-attenuated vaccines have long been sought as a method of choice for prevention. Yet their rational design and engineering have been thwarted by technical limitations. In addition, viral genes had not been identified that are needed to cause disease but can be deleted or substituted to generate live-attenuated vaccine strains. Lymphocytic choriomeningitis virus, the prototype arenavirus, induces cell-mediated immunity against Lassa fever virus, but its safety for humans is unclear and untested. Using this virus model, we have developed the necessary methodology to efficiently modify arenavirus genomes and have exploited these techniques to identify an arenaviral Achilles' heel suitable for targeting in vaccine design. Reverse genetic exchange of the viral glycoprotein for foreign glycoproteins created attenuated vaccine strains that remained viable although unable to cause disease in infected mice. This phenotype remained stable even after extensive propagation in immunodeficient hosts. Nevertheless, the engineered viruses induced T cell-mediated immunity protecting against overwhelming systemic infection and severe liver disease upon wild-type virus challenge. Protection was established within 3 to 7 d after immunization and lasted for approximately 300 d. The identification of an arenaviral Achilles' heel demonstrates that the reverse genetic engineering of live-attenuated arenavirus vaccines is feasible. Moreover, our findings offer lymphocytic choriomeningitis virus or other arenaviruses expressing foreign glycoproteins as promising live-attenuated arenavirus vaccine candidates.

Neurochemical and toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylpyridine to rat serotonin neurons in dissociated cell cultures

International Nuclear Information System (INIS)

Friedman, L.K.; Mytilineou, C.

1990-01-01

Dissociated cell cultures from the pontine area of embryonic rat brain were used to study the sensitivity of serotonin (5-hydroxy-tryptamine (5-HT)) neurons to the neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridine (MPP+). Treatment with MPTP (up to 100 microM) for 7 days did not cause degeneration of 5-HT neurons. A 50% inhibition of [3H]5-HT uptake caused by 100 microM MPTP was a direct effect on the 5-HT uptake carrier, reversed by washing for 7 days. Incubation of cultures with MPTP increased the intraneuronal levels of 5-HT and reduced the levels of 5-hydroxyindoleacetic acid, suggesting a reduction in 5-HT metabolism. MPTP reduced monoamine oxidase activity in the cultures, which probably led to the reduction in 5-HT metabolism. Exposure to MPP+ (0.5-10 microM) for 4 to 7 days decreased [3H]5-HT uptake and induced loss of neurons stained with antibodies against 5-HT. Comparison between 5-HT and dopamine (DA) neurons indicated a differential sensitivity to MPP+ toxicity with DA neurons being more susceptible. Analysis of the competition of MPP+ with the natural substrates for uptake sites of 5-HT and DA neurons demonstrated higher affinity of MPP+ for DA compared to 5-HT neurons. The lower affinity of MPP+ for 5-HT neurons could be responsible for the accumulation of lower MPP+ levels observed in pontine cultures and explain the resistance of 5-HT neurons to this toxin

Nuclear equipment to determine soil and water mass attenuation coefficients

International Nuclear Information System (INIS)

Zucchi, O.L.A.D.; Nascimento Filho, V.F. do

1984-01-01

The feasibility of substituting the monochannel gamma spectrometer, traditionally used in the gamma ray attenuation technique, for a less sophisticated and less expensive system of integral counting is studied. The proposed system can be operated by a non-specialized person. Three detection systems were used in the determination of the mass attenuation coefficients for different types of soil and for water. (M.A.C.) [pt

Qualitative evaluation of Chang method of attenuation correction on heart SPECT by using custom made heart phantom

International Nuclear Information System (INIS)

Takavar, A.; Eftekhari, M.; Beiki, D.; Saghari, M.; Mostaghim, N.; Sohrabi, M.

2003-01-01

SPECT detects γ- rays from administrated radiopharmaceutical within the patient body. γ-rays pass through different tissues before reaching detectors and are attenuated. Attenuation can cause artifacts; therefore different and used to minimize attenuation effects. In our study efficacy of Chang method was evaluated for attenuation purpose, using a custom made heart phantom. Due to different tissues surrounding heart, evaluation is not uniform more over activity distribution around heart is also non- uniform. In Chang method distribution of radioactivity and attenuation due to the surrounding tissue is considered uniform. Our phantom is a piece of plastic producing similar SPECT image as left ventricle. A dual head, ADAC system was used in our study. Images were taken by 180 d ig C (limited angle) and 360 d ig C (total rotation). Images are compared with and without attenuation correction. Our results indicate that Chang attenuation correction method is not capable of eliminating attenuation artifact completely in particular attenuation effects caused by breast

Transient attenuation in optical fibers

International Nuclear Information System (INIS)

Hopkins, A.A.; Kelly, R.E.; Looney, L.D.; Lyons, P.B.

1984-01-01

Low and high energy pulsed electron beams were used to generate radiation-induced transient attenuation in high-OH, Suprasil core, PCS fibers, demonstrating the energy dependence of the radiation damage and recovery mechanisms. A radiation resistant low-OH fiber was studied and its performance contrasted to that of high-OH materials. Several fibers with differing core compositions were also studied

Mass attenuation coefficient of chromium and manganese compounds around absorption edge.

Science.gov (United States)

Sharanabasappa; Kaginelli, S B; Kerur, B R; Anilkumar, S; Hanumaiah, B

2009-01-01

The total mass attenuation coefficient for Potassium dichromate, Potassium chromate and Manganese acetate compounds are measured at different photon energies 5.895, 6.404, 6.490, 7.058, 8.041 and 14.390 keV using Fe-55, Co-57 and 241Am source with Copper target, radioactive sources. The photon intensity is analyzed using a high resolution HPGe detector system coupled to MCA under good geometrical arrangement. The obtained values of mass attenuation coefficient values are compared with theoretical values. This study suggests that measured mass attenuation coefficient values at and near absorption edges differ from the theoretical value by about 5-28%.

Iterative methods for photoacoustic tomography in attenuating acoustic media

Science.gov (United States)

Haltmeier, Markus; Kowar, Richard; Nguyen, Linh V.

2017-11-01

The development of efficient and accurate reconstruction methods is an important aspect of tomographic imaging. In this article, we address this issue for photoacoustic tomography. To this aim, we use models for acoustic wave propagation accounting for frequency dependent attenuation according to a wide class of attenuation laws that may include memory. We formulate the inverse problem of photoacoustic tomography in attenuating medium as an ill-posed operator equation in a Hilbert space framework that is tackled by iterative regularization methods. Our approach comes with a clear convergence analysis. For that purpose we derive explicit expressions for the adjoint problem that can efficiently be implemented. In contrast to time reversal, the employed adjoint wave equation is again damping and, thus has a stable solution. This stability property can be clearly seen in our numerical results. Moreover, the presented numerical results clearly demonstrate the efficiency and accuracy of the derived iterative reconstruction algorithms in various situations including the limited view case.

Development of electrothermal actuation based planar variable optical attenuators (VOAs)

International Nuclear Information System (INIS)

Lee, Chengkuo; Yeh, J Andrew

2006-01-01

Several sorts of MEMS (Microelectromechanical Systems) based have been demonstrated by using electrostatic actuation scheme up to date. The comb drive and parallel plate are the two most common electrostatic actuators that have been well studied in variable optical attenuator (VOA) applications. In addition to the known retro-reflection type of optical attenuation being realized by our new devices driven by electrothermal actuators in present study, a novel planar tilted mirror with rotational and translation moving capability is proposed by using electrothermal actuators as well. Using electrothermal actuators to provide said planar tilted mirror with rotational and translational displacement has granted us a more efficient way to perform the light attenuation for in-plane structure. The static and transient characteristics of devices operated at ambient room temperature environment show good repeatability and stability

Effect of melatonin on methamphetamine- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity and methamphetamine-induced behavioral sensitization.

Science.gov (United States)

Itzhak, Y; Martin, J L; Black, M D; Ali, S F

1998-06-01

Methamphetamine (METH)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity is thought to be associated with the formation of free radicals. Since evidence suggests that melatonin may act as a free radical scavenger and antioxidant, the present study was undertaken to investigate the effect of melatonin on METH- and MPTP-induced neurotoxicity. In addition, the effect of melatonin on METH-induced locomotor sensitization was investigated. The administration of METH (5 mg kg(-1) x 3) or MPTP (20 mg kg(-1) x 3) to Swiss Webster mice resulted in 45-57% depletion in the content of striatal dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 57-59% depletion in dopamine transporter binding sites. The administration of melatonin (10 mg kg(-1)) before each of the three injections of the neurotoxic agents (on day 1), and thereafter for two additional days, afforded a full protection against METH-induced depletion of dopamine and its metabolites and dopamine transporter binding sites. In addition, melatonin significantly diminished METH-induced hyperthermia. However, the treatment with melatonin had no significant effect on MPTP-induced depletion of the dopaminergic markers tested. In the set of behavioral experiments, we found that the administration of 1 mg kg(-1) METH to Swiss Webster mice for 5 days resulted in marked locomotor sensitization to a subsequent challenge injection of METH, as well as context-dependent sensitization (conditioning). The pretreatment with melatonin (10 mg kg(-1)) prevented neither the sensitized response to METH nor the development of conditioned locomotion. Results of the present study indicate that melatonin has a differential effect on the dopaminergic neurotoxicity produced by METH and MPTP. Since it is postulated that METH-induced hyperthermia is related to its neurotoxic effect, while regulation of body temperature is unrelated to MPTP-induced neurotoxicity or METH

Multi-rate Poisson tree processes for single-locus species delimitation under maximum likelihood and Markov chain Monte Carlo.

Science.gov (United States)

Kapli, P; Lutteropp, S; Zhang, J; Kobert, K; Pavlidis, P; Stamatakis, A; Flouri, T

2017-06-01

In recent years, molecular species delimitation has become a routine approach for quantifying and classifying biodiversity. Barcoding methods are of particular importance in large-scale surveys as they promote fast species discovery and biodiversity estimates. Among those, distance-based methods are the most common choice as they scale well with large datasets; however, they are sensitive to similarity threshold parameters and they ignore evolutionary relationships. The recently introduced "Poisson Tree Processes" (PTP) method is a phylogeny-aware approach that does not rely on such thresholds. Yet, two weaknesses of PTP impact its accuracy and practicality when applied to large datasets; it does not account for divergent intraspecific variation and is slow for a large number of sequences. We introduce the multi-rate PTP (mPTP), an improved method that alleviates the theoretical and technical shortcomings of PTP. It incorporates different levels of intraspecific genetic diversity deriving from differences in either the evolutionary history or sampling of each species. Results on empirical data suggest that mPTP is superior to PTP and popular distance-based methods as it, consistently yields more accurate delimitations with respect to the taxonomy (i.e., identifies more taxonomic species, infers species numbers closer to the taxonomy). Moreover, mPTP does not require any similarity threshold as input. The novel dynamic programming algorithm attains a speedup of at least five orders of magnitude compared to PTP, allowing it to delimit species in large (meta-) barcoding data. In addition, Markov Chain Monte Carlo sampling provides a comprehensive evaluation of the inferred delimitation in just a few seconds for millions of steps, independently of tree size. mPTP is implemented in C and is available for download at http://github.com/Pas-Kapli/mptp under the GNU Affero 3 license. A web-service is available at http://mptp.h-its.org . : paschalia.kapli@h-its.org or

Broadband Vibration Attenuation Using Hybrid Periodic Rods

Directory of Open Access Journals (Sweden)

S. Asiri

2008-12-01

Full Text Available This paper presents both theoretically and experimentally a new kind of a broadband vibration isolator. It is a table-like system formed by four parallel hybrid periodic rods connected between two plates. The rods consist of an assembly of periodic cells, each cell being composed of a short rod and piezoelectric inserts. By actively controlling the piezoelectric elements, it is shown that the periodic rods can efficiently attenuate the propagation of vibration from the upper plate to the lower one within critical frequency bands and consequently minimize the effects of transmission of undesirable vibration and sound radiation. In such a system, longitudinal waves can propagate from the vibration source in the upper plate to the lower one along the rods only within specific frequency bands called the "Pass Bands" and wave propagation is efficiently attenuated within other frequency bands called the "Stop Bands". The spectral width of these bands can be tuned according to the nature of the external excitation. The theory governing the operation of this class of vibration isolator is presented and their tunable filtering characteristics are demonstrated experimentally as functions of their design parameters. This concept can be employed in many applications to control the wave propagation and the force transmission of longitudinal vibrations both in the spectral and spatial domains in an attempt to stop/attenuate the propagation of undesirable disturbances.

Clinical presentation of Attenuated Psychosis Syndrome in children and adolescents: Is there an age effect?

Science.gov (United States)

Ribolsi, Michele; Lin, Ashleigh; Wardenaar, Klaas J; Pontillo, Maria; Mazzone, Luigi; Vicari, Stefano; Armando, Marco

2017-06-01

There is limited research on clinical features related to age of presentation of the Attenuated Psychosis Syndrome in children and adolescents (CAD). Based on findings in CAD with psychosis, we hypothesized that an older age at presentation of Attenuated Psychosis Syndrome would be associated with less severe symptoms and better psychosocial functioning than presentation in childhood or younger adolescence. Ninety-four CAD (age 9-18) meeting Attenuated Psychosis Syndrome criteria participated in the study. The sample was divided and compared according to the age of presentation of Attenuated Psychosis Syndrome (9-14 vs 15-18 years). The predictive value of age of Attenuated Psychosis Syndrome presentation was investigated using receiver operating characteristic (ROC)-curve calculations. The two Attenuated Psychosis Syndrome groups were homogeneous in terms of gender distribution, IQ scores and comorbid diagnoses. Older Attenuated Psychosis Syndrome patients showed better functioning and lower depressive scores. ROC curves revealed that severity of functional impairment was best predicted using an age of presentation cut-off of 14.9 years for social functioning and 15.9 years for role functioning. This study partially confirmed our hypothesis; older age at presentation of Attenuated Psychosis Syndrome was associated with less functional impairment, but age was not associated with psychotic symptoms. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Attenuation correction for the collimated gamma ray assay of cylindrical samples

International Nuclear Information System (INIS)

Patra, Sabyasachi; Agarwal, Chhavi; Goswami, A.; Gathibandhe, M.

2015-01-01

The Hybrid Monte Carlo (HMC) method developed earlier for attenuation correction of non-collimated samples [Agarwal et al., 2008, Nucl. Instrum. Methods A 597, 198], has been extended to the segmented gamma ray assay of cylindrical samples. The method has been validated both experimentally and theoretically. For experimental validation, the results of HMC calculation have been compared with the experimentally obtained attenuation correction factors. The HMC attenuation correction factors have also been compared with the results obtained from literature available near-field and far-field formulae at two sample-to-detector distances (10.3 cm and 20.4 cm). The method has been found to be valid at all sample-to-detector distances over a wide range of transmittance. On the other hand, the literature available near-field and far-field formulae have been found to work over a limited range of sample-to detector distances and transmittances. The HMC method has been further extended to circular collimated geometries where analytical formula for attenuation correction does not exist. - Highlights: • Hybrid Monte Carlo method for attenuation correction developed for SGA system. • Method found to work for all sample-detector geometries for all transmittances. • The near-field formula applicable only after certain sample-detector distance. • The far-field formula applicable only for higher transmittances (>18%). • Hybrid Monte Carlo method further extended to circular collimated geometry

X-ray-based attenuation correction for positron emission tomography/computed tomography scanners.

Science.gov (United States)

Kinahan, Paul E; Hasegawa, Bruce H; Beyer, Thomas

2003-07-01

A synergy of positron emission tomography (PET)/computed tomography (CT) scanners is the use of the CT data for x-ray-based attenuation correction of the PET emission data. Current methods of measuring transmission use positron sources, gamma-ray sources, or x-ray sources. Each of the types of transmission scans involves different trade-offs of noise versus bias, with positron transmission scans having the highest noise but lowest bias, whereas x-ray scans have negligible noise but the potential for increased quantitative errors. The use of x-ray-based attenuation correction, however, has other advantages, including a lack of bias introduced from post-injection transmission scanning, which is an important practical consideration for clinical scanners, as well as reduced scan times. The sensitivity of x-ray-based attenuation correction to artifacts and quantitative errors depends on the method of translating the CT image from the effective x-ray energy of approximately 70 keV to attenuation coefficients at the PET energy of 511 keV. These translation methods are usually based on segmentation and/or scaling techniques. Errors in the PET emission image arise from positional mismatches caused by patient motion or respiration differences between the PET and CT scans; incorrect calculation of attenuation coefficients for CT contrast agents or metallic implants; or keeping the patient's arms in the field of view, which leads to truncation and/or beam-hardening (or x-ray scatter) artifacts. Proper interpretation of PET emission images corrected for attenuation by using the CT image relies on an understanding of the potential artifacts. In cases where an artifact or bias is suspected, careful inspection of all three available images (CT and PET emission with and without attenuation correction) is recommended. Copyright 2003 Elsevier Inc. All rights reserved.

Adrenal adenomas: relationship between histologic lipid-rich cells and CT attenuation number

International Nuclear Information System (INIS)

Yamada, Takayuki; Ishibashi, Tadashi; Saito, Haruo; Matsuhashi, Toshio; Majima, Kazuhiro; Tsuda, Masashi; Takahashi, Shoki; Moriya, Takuya

2003-01-01

Objective: To evaluate the relationship between lipid-rich cells of the adrenal adenoma and precontrast computed tomographic (CT) attenuation numbers in three clinical groups. Materials and Methods: Thirty-five surgically resected adrenal adenomas were used. The clinical diagnoses of the patients included 13 cases of primary aldosteronism, 15 cases of Cushing's syndrome, and 7 non-functioning tumors. The number of lipid-rich clear cells was counted using a microscopic eyepiece grid that contained 100 squares. The results were expressed as the percentages of lipid-rich areas. Results: There was a strong inverse linear relationship between the percentage of lipid-rich cells and the precontrast CT attenuation number (R 2 =0.724, P<0.0001). There were significantly more lipid-rich cells in the primary aldosteronism and non-functioning tumor cases compared to cases of Cushing's syndrome (P=0.007 and 0.015, respectively). The CT attenuation numbers of the primary aldosteronism cases were significantly lower than those of Cushing's syndrome (P=0.0052). Furthermore, the CT attenuation numbers of the non-functioning tumor cases were lower than those of Cushing's syndrome cases. Conclusion: We showed that adrenal adenomas in primary aldosteronism and non-functioning tumors contain significantly more lipid-rich cells than those in Cushing's syndrome. They also showed significantly lower attenuation than that in Cushing's syndrome on CT scans. Our results suggest that precontrast CT attenuation numbers may be helpful in the differentiation of adenomas from non-adenomatous lesions, which include malignancies

The development of an experimental set-up for the measurement of acoustic attenuation in sea-water and studies of the usefulness of acoustic attenuation as a parameter in oceanographic research

International Nuclear Information System (INIS)

Barkmann, R.

1982-01-01

A senson element is described for the measurement of ultrasound wave attenuation in water. This device has been developed for in-situ measurements of the additional attenuation caused by particles or air bubbles. Results are presented for the attenuation variations induced by ions and solid-state particles. The method is based on the emission of a 80 μs acoustic sine wave burst at about 10 MHz in a water container of 10 cm length. Then the amplitudes of the decaying echos are registrated, which are caused by reflections at the transducer and the reflector. The sound attenuation coefficient is obtained from the amplitude ratio of the first two echos, taking into account corrections caused by diffraction and reflection effects. (orig./RW) [de

Electron attenuation characteristics of LiF

Energy Technology Data Exchange (ETDEWEB)

Paliwal, B R [Wisconsin Univ., Madison (USA). Div. of Clinical Oncology; Almond, P R

1976-08-01

The results of a study, indicating the exponential nature of the attenuation of electrons in LiF, are reported. This conclusion holds good not only for the monoenergetic electrons obtained from several pure ..beta.. emitters but also for the high energy electron beams delivered by radiotherapy facilities.

Attenuation Model Using the Large-N Array from the Source Physics Experiment

Science.gov (United States)

Atterholt, J.; Chen, T.; Snelson, C. M.; Mellors, R. J.

2017-12-01

The Source Physics Experiment (SPE) consists of a series of chemical explosions at the Nevada National Security Site. SPE seeks to better characterize the influence of subsurface heterogeneities on seismic wave propagation and energy dissipation from explosions. As a part of this experiment, SPE-5, a 5000 kg TNT equivalent chemical explosion, was detonated in 2016. During the SPE-5 experiment, a Large-N array of 996 geophones (half 3-component and half z-component) was deployed. This array covered an area that includes loosely consolidated alluvium (weak rock) and weathered granite (hard rock), and recorded the SPE-5 explosion as well as 53 weight drops. We use these Large-N recordings to develop an attenuation model of the area to better characterize how geologic structures influence source energy partitioning. We found a clear variation in seismic attenuation for different rock types: high attenuation (low Q) for alluvium and low attenuation (high Q) for granite. The attenuation structure correlates well with local geology, and will be incorporated into the large simulation effort of the SPE program to validate predictive models. (LA-UR-17-26382)

Chlorine isotope investigation of natural attenuation of trichloroethene in an aerobic aquifer

International Nuclear Information System (INIS)

Sturchio, N.C.; Heraty, L.J.; Huang, L.; Holt, B.D.; Abrajano, T.A. Jr.; Clausen, J.L.

1998-01-01

Natural attenuation of chlorinated aliphatic hydrocarbons (CAHs) can be an important mechanism for groundwater remediation. It is difficult to determine the effectiveness of natural CAH attenuation from chemical analyses of groundwater samples because mixing, dispersion, and secondary reactions can mask the chemical evidence of attenuation. In this paper, the authors explore the application of stable chlorine isotope ratio measurements as a new tool for evaluating natural attenuation of CAHs. They report stable isotope ratios of chlorine in both trichloroethene (TCE) and inorganic chloride in groundwater from an aerobic aquifer beneath an extensively contaminated industrial site, the Paducah Gaseous Diffusion Plant in western Kentucky. Variations in the concentrations and chlorine isotope ratios of TCE and chloride in the groundwater are consistent with those expected from natural attenuation. These data support a model in which partial TCE degradation occurred in relatively impermeable, clay-rich sediments above the aquifer, and little or no further degradation of TCE occurred within the aquifer. A record of changing conditions within the TCE source area can be inferred from the spatial variation of chlorine isotope ratios for TCE and chloride within the plume

Influence of the electromagnetic parameters on the surface wave attenuation in thin absorbing layers

Science.gov (United States)

Li, Yinrui; Li, Dongmeng; Wang, Xian; Nie, Yan; Gong, Rongzhou

2018-05-01

This paper describes the relationships between the surface wave attenuation properties and the electromagnetic parameters of radar absorbing materials (RAMs). In order to conveniently obtain the attenuation constant of TM surface waves over a wide frequency range, the simplified dispersion equations in thin absorbing materials were firstly deduced. The validity of the proposed method was proved by comparing with the classical dispersion equations. Subsequently, the attenuation constants were calculated separately for the absorbing layers with hypothetical relative permittivity and permeability. It is found that the surface wave attenuation properties can be strongly tuned by the permeability of RAM. Meanwhile, the permittivity should be appropriate so as to maintain high cutoff frequency. The present work provides specific methods and designs to improve the attenuation performances of radar absorbing materials.

Combining nitric oxide release with anti-inflammatory activity preserves nigrostriatal dopaminergic innervation and prevents motor impairment in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease

Directory of Open Access Journals (Sweden)

Impagnatiello Francesco

2010-11-01

Full Text Available Abstract Background Current evidence suggests a role of neuroinflammation in the pathogenesis of Parkinson's disease (PD and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP model of basal ganglia injury. Reportedly, nonsteroidal anti-inflammatory drugs (NSAIDs mitigate DAergic neurotoxicity in rodent models of PD. Consistent with these findings, epidemiological analysis indicated that certain NSAIDs may prevent or delay the progression of PD. However, a serious impediment of chronic NSAID therapy, particularly in the elderly, is gastric, renal and cardiac toxicity. Nitric oxide (NO-donating NSAIDs, have a safer profile while maintaining anti-inflammatory activity of parent compounds. We have investigated the oral activity of the NO-donating derivative of flurbiprofen, [2-fluoro-α-methyl (1,1'-biphenyl-4-acetic-4-(nitrooxybutyl ester], HCT1026 (30 mg kg-1 daily in rodent chow in mice exposed to the parkinsonian neurotoxin MPTP. Methods Ageing mice were fed with a control, flurbiprofen, or HCT1026 diet starting ten days before MPTP administration and continuing for all the experimental period. Striatal high affinity synaptosomial dopamine up-take, motor coordination assessed with the rotarod, tyrosine hydroxylase (TH- and dopamine transporter (DAT fiber staining, stereological cell counts, immunoblotting and gene expression analyses were used to assess MPTP-induced nigrostriatal DAergic toxicity and glial activation 1-40 days post-MPTP. Results HCT1026 was well tolerated and did not cause any measurable toxic effect, whereas flurbiprofen fed mice showed severe gastrointestinal side-effects. HCT1026 efficiently counteracted motor impairment and reversed MPTP-induced decreased synaptosomal [3H]dopamine uptake, TH- and DAT-stained fibers in striatum and TH+ neuron loss in subtantia nigra pars compacta (SNpc, as opposed to age-matched mice fed with a control diet. These effects were associated to a significant decrease in reactive

Direct Reconstruction of CT-based Attenuation Correction Images for PET with Cluster-Based Penalties

Science.gov (United States)

Kim, Soo Mee; Alessio, Adam M.; De Man, Bruno; Asma, Evren; Kinahan, Paul E.

2015-01-01

Extremely low-dose CT acquisitions for the purpose of PET attenuation correction will have a high level of noise and biasing artifacts due to factors such as photon starvation. This work explores a priori knowledge appropriate for CT iterative image reconstruction for PET attenuation correction. We investigate the maximum a posteriori (MAP) framework with cluster-based, multinomial priors for the direct reconstruction of the PET attenuation map. The objective function for direct iterative attenuation map reconstruction was modeled as a Poisson log-likelihood with prior terms consisting of quadratic (Q) and mixture (M) distributions. The attenuation map is assumed to have values in 4 clusters: air+background, lung, soft tissue, and bone. Under this assumption, the MP was a mixture probability density function consisting of one exponential and three Gaussian distributions. The relative proportion of each cluster was jointly estimated during each voxel update of direct iterative coordinate decent (dICD) method. Noise-free data were generated from NCAT phantom and Poisson noise was added. Reconstruction with FBP (ramp filter) was performed on the noise-free (ground truth) and noisy data. For the noisy data, dICD reconstruction was performed with the combination of different prior strength parameters (β and γ) of Q- and M-penalties. The combined quadratic and mixture penalties reduces the RMSE by 18.7% compared to post-smoothed iterative reconstruction and only 0.7% compared to quadratic alone. For direct PET attenuation map reconstruction from ultra-low dose CT acquisitions, the combination of quadratic and mixture priors offers regularization of both variance and bias and is a potential method to derive attenuation maps with negligible patient dose. However, the small improvement in quantitative accuracy relative to the substantial increase in algorithm complexity does not currently justify the use of mixture-based PET attenuation priors for reconstruction of CT

Attenuated Vector Tomography -- An Approach to Image Flow Vector Fields with Doppler Ultrasonic Imaging

International Nuclear Information System (INIS)

Huang, Qiu; Peng, Qiyu; Huang, Bin; Cheryauka, Arvi; Gullberg, Grant T.

2008-01-01

The measurement of flow obtained using continuous wave Doppler ultrasound is formulated as a directional projection of a flow vector field. When a continuous ultrasound wave bounces against a flowing particle, a signal is backscattered. This signal obtains a Doppler frequency shift proportional to the speed of the particle along the ultrasound beam. This occurs for each particle along the beam, giving rise to a Doppler velocity spectrum. The first moment of the spectrum provides the directional projection of the flow along the ultrasound beam. Signals reflected from points further away from the detector will have lower amplitude than signals reflected from points closer to the detector. The effect is very much akin to that modeled by the attenuated Radon transform in emission computed tomography.A least-squares method was adopted to reconstruct a 2D vector field from directional projection measurements. Attenuated projections of only the longitudinal projections of the vector field were simulated. The components of the vector field were reconstructed using the gradient algorithm to minimize a least-squares criterion. This result was compared with the reconstruction of longitudinal projections of the vector field without attenuation. If attenuation is known, the algorithm was able to accurately reconstruct both components of the full vector field from only one set of directional projection measurements. A better reconstruction was obtained with attenuation than without attenuation implying that attenuation provides important information for the reconstruction of flow vector fields.This confirms previous work where we showed that knowledge of the attenuation distribution helps in the reconstruction of MRI diffusion tensor fields from fewer than the required measurements. In the application of ultrasound the attenuation distribution is obtained with pulse wave transmission computed tomography and flow information is obtained with continuous wave Doppler

[Comparison of chemical quality characteristics between radial striations and non-radial striations in tuberous root of Rehmannia glutinosa].

Science.gov (United States)

Xie, Cai-Xia; Zhang, Miao; Li, Ya-Jing; Geng, Xiao-Tong; Wang, Feng-Qing; Zhang, Zhong-Yi

2017-11-01

An HPLC method was established to determine the contents of catalpol, acteoside, rehmaionoside A, rehmaionoside D, leonuride in three part of Rehmanni glutinosa in Beijing No.1 variety R. glutinosa during the growth period, This method, in combination with its HPLC fingerprint was used to evaluate its overall quality characteristics.The results showed that：① the content of main components of R. glutinosa varied in different growth stages ;② there was a great difference of the content of main components between theradial striations and the non-radial striations; ③ the two sections almost have the same content distribution of catalpol, acteoside and rehmaionoside D; ④the content of rehmaionoside A in non-radial striations was higher than that in radial striations,while the content of leonuride in radial striations was higher than that in non-radial striations.; ⑤the HPLC fingerprint of radial striations, non-radial striations and whole root tuber were basically identical, except for the big difference in the content of chemical components. The result of clustering displayed that the radial striations, non-radial striations, and whole root were divided into two groups. In conclusion, there was a significant difference in the quality characteristics of radial striations and non-radial striations of R. glutinosa. This research provides a reference for quality evaluation and geoherbalism of R. glutinosa. Copyright© by the Chinese Pharmaceutical Association.

Nectar microbes can reduce secondary metabolites in nectar and alter effects on nectar consumption by pollinators.

Science.gov (United States)

Vannette, Rachel L; Fukami, Tadashi

2016-06-01

Secondary metabolites that are present in floral nectar have been hypothesized to enhance specificity in plant-pollinator mutualism by reducing larceny by non-pollinators, including microorganisms that colonize nectar. However, few studies have tested this hypothesis. Using synthetic nectar, we conducted laboratory and field experiments to examine the effects of five chemical compounds found in nectar on the growth and metabolism of nectar-colonizing yeasts and bacteria, and the interactive effects of these compounds and nectar microbes on the consumption of nectar by pollinators. In most cases, focal compounds inhibited microbial growth, but the extent of these effects depended on compound identity, concentration, and microbial species. Moreover, most compounds did not substantially decrease sugar metabolism by microbes, and microbes reduced the concentration of some compounds in nectar. Using artificial flowers in the field, we also found that the common nectar yeast Metschnikowia reukaufii altered nectar consumption by small floral visitors, but only in nectar containing catalpol. This effect was likely mediated by a mechanism independent of catalpol metabolism. Despite strong compound-specific effects on microbial growth, our results suggest that the secondary metabolites tested here are unlikely to be an effective general defense mechanism for preserving nectar sugars for pollinators. Instead, our results indicate that microbial colonization of nectar could reduce the concentration of secondary compounds in nectar and, in some cases, reduce deterrence to pollinators.

Dexmedetomidine in premedication to attenuate the acute ...

African Journals Online (AJOL)

Background: The choice of anaesthetic agent for electroconvulsive therapy (ECT) depends on seizure duration, haemodynamic ... and infarction. To attenuate this acute ... scheduled for ECT, physical status ASA I and II, age between 18 and.

Calculation of noise attenuation coefficient for leaks in the system sodium-water

International Nuclear Information System (INIS)

Yugaj, V.S.; Kozlov, F.A.; Sorokina, T.G.

1986-01-01

In this report the authors present the calculation results for sound attenuation coefficient on hydrogen bubbles in sodium and show a calculation method of attenuation coefficient for different temperatures of sodium in the 1-200 kHz range frequencies [fr

Polymer composites with carbon nanotube for application of radiation attenuator in medical procedures

Energy Technology Data Exchange (ETDEWEB)

Fontainha, C.C.P.; Nunes, M.; Rosas, V.A., E-mail: crissia@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Anatomia e Imagem; Furtado, C.A.; Faria, L.O. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

2017-07-01

Medical radiology offers great benefit to patients, however, the radiation contributes for the workers and individuals exposure, significantly increasing dose to population. New attenuators materials have been widely investigated for radiation shielding to apply in medical procedures. Polymeric composites filled with attenuating metals and functionalized with carbon nanotubes (NTC) are being largely developed. In this work, composites were produced for radiation attenuation in radiodiagnostic imaging procedures. Two types of polymer matrices, polyvinylidene fluoride, PVDF, and its copolymer, poly(vinylidene-trifluorylene fluoride), P(VDF-TrFE), were filled bismuth oxide nanoparticles. Carbon nanotubes were added with different concentrations at the solution of attenuator metal under controlled magnetic stirring. The composites were characterized by differential heat flow scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and dispersive energy X-ray spectrometry (EDS) for thermal analysis. In this setup, one reference measure is directly exposed to the x-rays being diffracted by single crystal of Si (111). Another measure the attenuated beam is performed with the composite sample under detector. The samples present a good dispersion of the attenuator metal and the nanotube carbon. On the other hand, composites with PVDF matrix lost their plasticity, stiffening their structure, becoming brittle, even using the same methodology of synthesis. The P(VDF-Trfe) matrix showed better maleability than PVDF matrix. The cheaptube dispersion in the P(VDF-Trfe) matrix presented better than the 3100 carbon nanotubes. The attenuation for 8.047 keV monoenergetic photons was about 90% to 100 μm thickness for all composites. (author)

Polymer composites with carbon nanotube for application of radiation attenuator in medical procedures

International Nuclear Information System (INIS)

Fontainha, C.C.P.; Nunes, M.; Rosas, V.A.

2017-01-01

Medical radiology offers great benefit to patients, however, the radiation contributes for the workers and individuals exposure, significantly increasing dose to population. New attenuators materials have been widely investigated for radiation shielding to apply in medical procedures. Polymeric composites filled with attenuating metals and functionalized with carbon nanotubes (NTC) are being largely developed. In this work, composites were produced for radiation attenuation in radiodiagnostic imaging procedures. Two types of polymer matrices, polyvinylidene fluoride, PVDF, and its copolymer, poly(vinylidene-trifluorylene fluoride), P(VDF-TrFE), were filled bismuth oxide nanoparticles. Carbon nanotubes were added with different concentrations at the solution of attenuator metal under controlled magnetic stirring. The composites were characterized by differential heat flow scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and dispersive energy X-ray spectrometry (EDS) for thermal analysis. In this setup, one reference measure is directly exposed to the x-rays being diffracted by single crystal of Si (111). Another measure the attenuated beam is performed with the composite sample under detector. The samples present a good dispersion of the attenuator metal and the nanotube carbon. On the other hand, composites with PVDF matrix lost their plasticity, stiffening their structure, becoming brittle, even using the same methodology of synthesis. The P(VDF-Trfe) matrix showed better maleability than PVDF matrix. The cheaptube dispersion in the P(VDF-Trfe) matrix presented better than the 3100 carbon nanotubes. The attenuation for 8.047 keV monoenergetic photons was about 90% to 100 μm thickness for all composites. (author)

Measurement of attenuation cross-sections of some fatty acids in the ...

Indian Academy of Sciences (India)

These quantities were obtained by utilizing experimentally measured values of mass attenuation coefficients ( μ m ) . A NaI(Tl) scintillation detector with 8.2% (at 662 keV) resolution was used for detecting of attenuated γ -photons. The variation in Zeff and Neff of fatty acids with energy is discussed. The experimental and ...

Dehydroepiandrosterone Attenuates Cocaine-Seeking Behaviour Independently of Corticosterone Fluctuations.

Science.gov (United States)

Maayan, R; Hirsh, L; Yadid, G; Weizman, A

2015-11-01

The neurosteroid dehydroepiandrosterone (DHEA) is involved in the pathophysiology of several psychiatric disorders, including cocaine addiction. We have previously shown that DHEA attenuates cocaine-seeking behaviour, and also that DHEA decreases corticosterone (CORT) levels in plasma and the prefrontal cortex. Previous studies have found that rats demonstrate cocaine-seeking behaviour only when the level of CORT reaches a minimum threshold. In the present study, we investigated whether the attenuating effect of DHEA on cocaine seeking is a result of it reducing CORT levels rather than a result of any unique neurosteroid properties. Rats received either daily DHEA injections (2 mg/kg, i.p.) alone, daily DHEA (2 mg/kg, i.p.) with CORT infusion (to maintain stable basal levels of CORT; 15 mg/kg, s.c.) or vehicle (i.p.) as control, throughout self-administration training and extinction sessions. We found that both DHEA-treated and DHEA + CORT-treated groups showed a significantly lower number of active lever presses compared to controls throughout training and extinction sessions, as well as at cocaine-primed reinstatement. DHEA-treated rats showed lower CORT levels throughout the experimental phases compared to DHEA + CORT-treated and control rats. Additionally, we show that DHEA administered to cocaine-trained rats throughout extinction sessions, or immediately before reinstatement, attenuated cocaine seeking. These findings indicate that DHEA attenuates cocaine-seeking behaviour independently of fluctuations in CORT levels. © 2015 British Society for Neuroendocrinology.

Antisporozoite antibodies in mice immunized with irradiation-attenuated Plasmodium berghei sporozoites

International Nuclear Information System (INIS)

Hansen, R.; Silva, S.de; Strickland, G.T.

1979-01-01

Sera from NMRI/NIH mice were tested for the presence of IgM and IgG anti-sporozoite antibodies using the indirect fluorescent antibody test (IFAT). Both IgM and IgG antibody titres were related to the number of immunizations with irradiation-attenuated Plasmodium berghei sporozoites, and protection from challenge with subsequent non-attenuated sporozoites correlated with the pre-challenge antibody titre. Sera taken five days following challenge showed marked reductions in antibody titres, except for the group receiving the maximum (four) immunizations. Groups immunized with frozen sporozoites or mosquito tissue antigen developed neither antibodies to sporozoites nor protective immunity; nor did animals infected with parasitized blood. However, sera from mice immunized four times with attenuated sporozoites demonstrated IFA titres to blood-stage antigens. The results showed that both IgM and IgG anti-sporozoite antibodies could be detected in mice immunized with attenuated-sporozoites by IFAT, and that the antibody titres correlated with protective immunity. Cross reaction with blood-stage antigens occurred, but the test should still prove useful. (author)

On the Attenuation of Neutrons and Photons in a Duct Filled with a Helical Plug

Energy Technology Data Exchange (ETDEWEB)