Science.gov

Sample records for administration significantly attenuated

  1. Significant Attenuation of Lightly Damped Resonances Using Particle Dampers

    NASA Technical Reports Server (NTRS)

    Smith, Andrew; LaVerde, Bruce; Hunt, Ron; Knight, Joseph Brent

    2015-01-01

    When equipment designs must perform in a broad band vibration environment it can be difficult to avoid resonances that affect life and performance. This is especially true when an organization seeks to employ an asset from a heritage design in a new, more demanding vibration environment. Particle dampers may be used to provide significant attenuation of lightly damped resonances to assist with such a deployment of assets by including only a very minor set of modifications. This solution may be easier to implement than more traditional attenuation schemes. Furthermore, the cost in additional weight to the equipment can be very small. Complexity may also be kept to a minimum, because the particle dampers do not require tuning. Attenuating the vibratory response with particle dampers may therefore be simpler (in a set it and forget it kind of way) than tuned mass dampers. The paper will illustrate the use of an "equivalent resonance test jig" that can assist designers in verifying the potential resonance attenuation that may be available to them during the early trade stages of the design. An approach is suggested for transforming observed attenuation in the jig to estimated performance in the actual service design. KEY WORDS: Particle Damper, Performance in Vibration Environment, Damping, Resonance, Attenuation, Mitigation of Vibration Response, Response Estimate, Response Verification.

  2. Subchronic SSRI administration attenuates insula response during affective anticipation

    PubMed Central

    Simmons, Alan N.; Arce, Estibaliz; Lovero, Kathryn L.; Stein, Murray B.; Paulus, Martin P.

    2010-01-01

    Context The anterior cingulate cortex (ACC) and insula are important neural substrates for the integration of cognitive, emotional, and physiological information, as well as the coordination of responses to anticipated stimuli. Increased neural activation within these structures has been observed in individuals with anxiety and depressive disorders. Selective serotonin reuptake inhibitors (SSRIs) are among the most effective and frequently prescribed anxiolytic agents, yet it is not known whether ACC or insula underlie the effects of these drugs. We examined whether subchronic administration of an SSRI to healthy volunteers attenuate activation in ACC or insula during anticipation, an important emotional process underlying anxiety. Support for this hypothesis would help to understand where and by what process SSRIs may exert beneficial effects as anxiolytics and would provide further mechanistic evidence for functional magnetic resonance imaging (fMRI) as a biomarker for the development of anxiolytics. Participants and Design 15 volunteers participated in a double-blind, placebo-controlled, randomized cross-over study. Participants completed a pleasant and aversive picture cued anticipation task during fMRI after taking either escitalopram (10 mg) or placebo for 21 days. Main Outcome Measure Percent BOLD signal change during SSRI administration. Results Escitalopram significantly decreased activation in bilateral posterior and middle insula during the anticipation condition irrespective of stimulus valence and in medial prefrontal and ACC during anticipation of aversive versus pleasant images. Conclusion Reduced insular and ACC activation during anticipation may be integral to the therapeutic efficacy of SSRIs and provide a mechanistic approach for the use of pharmacofMRI in the identification of novel pharmacotherapeutic agents. PMID:19545475

  3. Nicotine Administration Attenuates Methamphetamine-Induced Novel Object Recognition Deficits

    PubMed Central

    Vieira-Brock, Paula L.; McFadden, Lisa M.; Nielsen, Shannon M.; Smith, Misty D.; Hanson, Glen R.

    2015-01-01

    Background: Previous studies have demonstrated that methamphetamine abuse leads to memory deficits and these are associated with relapse. Furthermore, extensive evidence indicates that nicotine prevents and/or improves memory deficits in different models of cognitive dysfunction and these nicotinic effects might be mediated by hippocampal or cortical nicotinic acetylcholine receptors. The present study investigated whether nicotine attenuates methamphetamine-induced novel object recognition deficits in rats and explored potential underlying mechanisms. Methods: Adolescent or adult male Sprague-Dawley rats received either nicotine water (10–75 μg/mL) or tap water for several weeks. Methamphetamine (4×7.5mg/kg/injection) or saline was administered either before or after chronic nicotine exposure. Novel object recognition was evaluated 6 days after methamphetamine or saline. Serotonin transporter function and density and α4β2 nicotinic acetylcholine receptor density were assessed on the following day. Results: Chronic nicotine intake via drinking water beginning during either adolescence or adulthood attenuated the novel object recognition deficits caused by a high-dose methamphetamine administration. Similarly, nicotine attenuated methamphetamine-induced deficits in novel object recognition when administered after methamphetamine treatment. However, nicotine did not attenuate the serotonergic deficits caused by methamphetamine in adults. Conversely, nicotine attenuated methamphetamine-induced deficits in α4β2 nicotinic acetylcholine receptor density in the hippocampal CA1 region. Furthermore, nicotine increased α4β2 nicotinic acetylcholine receptor density in the hippocampal CA3, dentate gyrus and perirhinal cortex in both saline- and methamphetamine-treated rats. Conclusions: Overall, these findings suggest that nicotine-induced increases in α4β2 nicotinic acetylcholine receptors in the hippocampus and perirhinal cortex might be one mechanism by which

  4. Cannabinoid administration attenuates the progression of simian immunodeficiency virus.

    PubMed

    Molina, Patricia E; Winsauer, Peter; Zhang, Ping; Walker, Edith; Birke, Leslie; Amedee, Angela; Stouwe, Curtis Vande; Troxclair, Dana; McGoey, Robin; Varner, Kurt; Byerley, Lauri; LaMotte, Lynn

    2011-06-01

    Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), the primary psychoactive component in marijuana, is FDA approved to ameliorate AIDS-associated wasting. Because cannabinoid receptors are expressed on cells of the immune system, chronic Δ(9)-THC use may impact HIV disease progression. We examined the impact of chronic Δ(9)-THC administration (0.32 mg/kg im, 2 × daily), starting 28 days prior to inoculation with simian immunodeficiency virus (SIV(mac251); 100 TCID(50)/ml, iv), on immune and metabolic indicators of disease during the initial 6 month asymptomatic phase of infection in rhesus macaques. SIV(mac251) inoculation resulted in measurable viral load, decreased lymphocyte CD4(+)/CD8(+) ratio, and increased CD8(+) proliferation. Δ(9)-THC treatment of SIV-infected animals produced minor to no effects in these parameters. However, chronic Δ(9)-THC administration decreased early mortality from SIV infection (p = 0.039), and this was associated with attenuation of plasma and CSF viral load and retention of body mass (p = NS). In vitro, Δ(9)-THC (10 μm) decreased SIV (10 TCID(50)) viral replication in MT4-R5 cells. These results indicate that chronic Δ(9)-THC does not increase viral load or aggravate morbidity and may actually ameliorate SIV disease progression. We speculate that reduced levels of SIV, retention of body mass, and attenuation of inflammation are likely mechanisms for Δ(9)-THC-mediated modulation of disease progression that warrant further study.

  5. Intrastriatal gene delivery of GDNF persistently attenuates methamphetamine self-administration and relapse in mice.

    PubMed

    Yan, Yijin; Miyamoto, Yoshiaki; Nitta, Atsumi; Muramatsu, Shin-Ichi; Ozawa, Keiya; Yamada, Kiyofumi; Nabeshima, Toshitaka

    2013-08-01

    Relapse of drug abuse after abstinence is a major challenge to the treatment of addicts. In our well-established mouse models of methamphetamine (Meth) self-administration and reinstatement, bilateral microinjection of adeno-associated virus vectors expressing GDNF (AAV-Gdnf) into the striatum significantly reduced Meth self-administration, without affecting locomotor activity. Moreover, the intrastriatal AAV-Gdnf attenuated cue-induced reinstatement of Meth-seeking behaviour in a sustainable manner. In addition, this manipulation showed that Meth-primed reinstatement of Meth-seeking behaviour was reduced. These findings suggest that the AAV vector-mediated Gdnf gene transfer into the striatum is an effective and sustainable approach to attenuate Meth self-administration and Meth-associated cue-induced relapsing behaviour and that the AAV-mediated Gdnf gene transfer in the brain may be a valuable gene therapy against drug dependence and protracted relapse in clinical settings.

  6. Adenosine 2A receptor agonism: A single intrathecal administration attenuates motor paralysis in experimental autoimmune encephalopathy in rats.

    PubMed

    Loram, Lisa C; Strand, Keith A; Taylor, Frederick R; Sloane, Evan; Van Dam, Anne-Marie; Rieger, Jayson; Maier, Steven F; Watkins, Linda R

    2015-05-01

    A single intrathecal dose of adenosine 2A receptor (A2AR) agonist was previously reported to produce a multi-week reversal of allodynia in two different models of neuropathic pain in addition to downregulating glial activation markers in the spinal cord. We aimed to determine whether a single intrathecal administration of an A2AR agonist was able to attenuate motor symptoms induced by experimental autoimmune encephalopathy. Two A2AR agonists (CGS21680 and ATL313) significantly attenuated progression of motor symptoms following a single intrathecal administration at the onset of motor symptoms. OX-42, a marker of microglial activation, was significantly attenuated in the lumbar spinal cord following A2AR administration compared to vehicle. Therefore, A2AR agonists attenuate motor symptoms of EAE by acting on A2AR in the spinal cord.

  7. Oxytocin administration attenuates stress reactivity in borderline personality disorder: a pilot study.

    PubMed

    Simeon, D; Bartz, J; Hamilton, H; Crystal, S; Braun, A; Ketay, S; Hollander, E

    2011-10-01

    Oxytocin has known stress-reducing and attachment-enhancing effects. We thus hypothesized that oxytocin would attenuate emotional and hormonal responses to stress in borderline personality disorder (BPD). Fourteen BPD and 13 healthy control (HC) adults received 40 IU intranasal oxytocin or placebo in double-blind randomized order followed by the Trier Social Stress Test. Subjective dysphoria (Profile of Mood Changes) and plasma cortisol levels were measured. Childhood trauma history, attachment style, and self-esteem were also rated. A significant "Group × Drug × Time" interaction effect for dysphoria (p=.04) reflected a proportionately greater attenuation of stress-induced dysphoria in the BPD group after oxytocin administration. Additionally, a marginally significant "Group × Drug" interaction effect for cortisol (p=.10) reflected a tendency toward greater attenuation of the stress-induced cortisol surge in the BPD group after oxytocin administration. In the combined sample, the oxytocin-placebo difference in the emotional stress reactivity was significantly predicted by childhood trauma alone (p=.037) and combined with self-esteem (p=.030), whereas the oxytocin-placebo difference in cortisol stress reactivity was predicted only by insecure attachment (p=.013). Results suggest that oxytocin may have a beneficial impact on emotional regulation in BPD, which merits further investigation and could have important treatment implications.

  8. Low dose naltrexone administration in morphine dependent rats attenuates withdrawal-induced norepinephrine efflux in forebrain.

    PubMed

    Van Bockstaele, Elisabeth J; Qian, Yaping; Sterling, Robert C; Page, Michelle E

    2008-05-15

    The administration of low dose opioid antagonists has been explored as a potential means of detoxification in opiate dependence. Previous results from our laboratory have shown that concurrent administration of low dose naltrexone in the drinking water of rats implanted with subcutaneous morphine pellets attenuates behavioral and biochemical signs of withdrawal in brainstem noradrenergic nuclei. Noradrenergic projections originating from the nucleus tractus solitarius (NTS) and the locus coeruleus (LC) have previously been shown to be important neural substrates involved in the somatic expression of opiate withdrawal. The hypothesis that low dose naltrexone treatment attenuates noradrenergic hyperactivity typically associated with opiate withdrawal was examined in the present study by assessing norepinephrine tissue content and norepinephrine efflux using in vivo microdialysis coupled to high performance liquid chromatography (HPLC) with electrochemical detection (ED). The frontal cortex (FC), amygdala, bed nucleus of the stria terminalis (BNST) and cerebellum were analyzed for tissue content of norepinephrine following withdrawal in morphine dependent rats. Naltrexone-precipitated withdrawal elicited a significant decrease in tissue content of norepinephrine in the BNST and amygdala. This decrease was significantly attenuated in the BNST of rats that received low dose naltrexone pre-treatment compared to controls. No significant difference was observed in the other brain regions examined. In a separate group of rats, norepinephrine efflux was assessed with in vivo microdialysis in the BNST or the FC of morphine dependent rats or placebo treated rats subjected to naltrexone-precipitated withdrawal that received either naltrexone in their drinking water (5 mg/L) or unadulterated water. Following baseline dialysate collection, withdrawal was precipitated by injection of naltrexone and sample collection continued for an additional 4 h. At the end of the experiment

  9. Exogenous NAD+ administration significantly protects against myocardial ischemia/reperfusion injury in rat model

    PubMed Central

    Zhang, Youjun; Wang, Ban; Fu, Xingli; Guan, Shaofeng; Han, Wenzheng; Zhang, Jie; Gan, Qian; Fang, Weiyi; Ying, Weihai; Qu, Xinkai

    2016-01-01

    Acute myocardial infarction is one of the leading causes for death around the world. Although essential for successful interventional therapy, it is inevitably complicated by reperfusion injury. Thus effective approaches to reduce ischemia/reperfusion (I/R) injury are still critically needed. To test our hypothesis that intravenous administration of NAD+ can attenuate I/R injury by reducing apoptotic damage and enhancing antioxidant capacity, we used a rat mode of myocardial I/R. Our study found that administration of 10-20 mg/kg NAD+ can dose dependently reduce myocardial infarct induced by I/R, with an approximately 85% reduction of the infarct at the dosage of 20 mg/kg NAD+. We further found that the injection of NAD+ can significantly decrease I/R-induced apoptotic damage in the heart: NAD+ administration can both decrease the TUNEL signals, Bax, cleaved caspase-3 levels and increase the Bcl-XL levels in the rats that are subjected to myocardial I/R injury. NAD+ administration can also significantly attenuate I/R-induced decreases in SOD activity and SOD-2 protein levels in the hearts. NAD+ can profoundly decrease myocardial I/R injury at least partially by attenuating apoptotic damage and enhancing the antioxidant capacity, thus suggesting that NAD+ may become a promising therapeutic agent for myocardial I/R injury. PMID:27648125

  10. The role of excessive versus acute administration of erythropoietin in attenuating hepatic ischemia-reperfusion injury.

    PubMed

    Pappo, Orit; Ben-Ari, Ziv; Shevtsov, Evgeni; Avlas, Orna; Gassmann, Max; Ravid, Amiram; Cheporko, Yelena; Hochhauser, Edith

    2010-12-01

    Ischemia-reperfusion injury (I/R) is the main cause of primary graft nonfunction. Our aim was to evaluate the effect of excessive versus acute administration of erythropoietin (EPO) in attenuating the hepatic injury induced by I/R in mice. The effect of segmental (70%) hepatic ischemia was evaluated in a transgenic mouse line with constitutive overexpression of human EPO cDNA and in wild-type (WT) mice. Mice were randomly allocated to 5 main experimental groups: (i) WT-sham, (ii) WT ischemia, (iii) WT ischemia + recombinant human erythropoietin (rhEPO), (iv) transgenic-sham, and (v) transgenic ischemia. The EPO-pretreated mice showed a significant reduction in liver enzyme levels and intrahepatic caspase-3 activity and fewer apoptotic hepatocytes (p < 0.05 for all) compared with the WT untreated I/R group. EPO decreased c-Jun N-terminal kinase (JNK) phosphorylation and nuclear factor-κB (NF-κB) expression during I/R. In transgenic I/R livers, baseline histology showed diffused hepatic injury, and no significant beneficial effect was noted between the WT untreated and the transgenic I/R mice. In conclusion, acute pretreatment with EPO in WT mice attenuated in vivo I/R liver injury. However, in excessive EPO overexpression, the initial liver injury abolished the beneficial effect of EPO. These findings have important implications for the potential use of acute EPO in I/R injury during liver transplantation.

  11. A neurotensin analog, NT69L, attenuates intravenous nicotine self-administration in rats.

    PubMed

    Boules, Mona; Oliveros, Alfredo; Liang, Yanqi; Williams, Katrina; Shaw, Amanda; Robinson, Jessica; Fredrickson, Paul; Richelson, Elliott

    2011-02-01

    NT69L is a neurotensin analog that blocks nicotine-induced locomotor activity and has sustained efficacy in a rat model of nicotine-induced sensitization when administered peripherally. Additionally, NT69L attenuates food-reinforcement in rats. The present study tested the effect of acute administration of NT69L on nicotine self-infusion in Sprague-Dawley rats. Rats were trained to self-infuse nicotine intravenously (0.03mg/kg per infusion) following operant training. Once the rats acquired stable responding to nicotine self-infusion they were pretreated with NT69L (1mg/kg, i.p.) or saline 30min before being assessed for nicotine self-infusion. Pretreatment with NT69L significantly attenuated nicotine self-infusion under FR1 (fixed ratio of 1) and FR5 schedule of reinforcement as compared to saline pretreatment. Control rats that were response-independent "yoked" as well as rats that self-infused saline or NT69L showed minimal responses, indicating that nicotine served as a reinforcer. Additionally, NT69L modulated serum corticosterone; brain norepinephrine serotonin; and dopamine receptors mRNA levels altered in the nicotine self-infused rats after a 24h withdrawal period. Pretreatment with NT69L significantly decreased the nicotine-induced increase in serum corticosterone levels and striatal norepinephrine and increased the nicotine-induced reduction in serotonin in both the striatum and the prefrontal cortex (PFC). NT69L might modulate dopamine neurotransmission implicated in the reinforcing effects of nicotine by modulating tyrosine hydroxylase and dopamine receptor mRNA levels in the PFC and striatum. These data support further study of the effects of NT analogs on attenuating the reinforcing effects of psychostimulants.

  12. Sarin-induced brain damage in rats is attenuated by delayed administration of midazolam.

    PubMed

    Chapman, Shira; Yaakov, Guy; Egoz, Inbal; Rabinovitz, Ishai; Raveh, Lily; Kadar, Tamar; Gilat, Eran; Grauer, Ettie

    2015-07-01

    Sarin poisoned rats display a hyper-cholinergic activity including hypersalivation, tremors, seizures and death. Here we studied the time and dose effects of midazolam treatment following nerve agent exposure. Rats were exposed to sarin (1.2 LD50, 108 μg/kg, im), and treated 1 min later with TMB4 and atropine (TA 7.5 and 5 mg/kg, im, respectively). Midazolam was injected either at 1 min (1 mg/kg, im), or 1 h later (1 or 5 mg/kg i.m.). Cortical seizures were monitored by electrocorticogram (ECoG). At 5 weeks, rats were assessed in a water maze task, and then their brains were extracted for biochemical analysis and histological evaluation. Results revealed a time and dose dependent effects of midazolam treatment. Rats treated with TA only displayed acute signs of sarin intoxication, 29% died within 24h and the ECoG showed seizures for several hours. Animals that received midazolam within 1 min survived with only minor clinical signs but with no biochemical, behavioral, or histological sequel. Animals that lived to receive midazolam at 1h (87%) survived and the effects of the delayed administration were dose dependent. Midazolam 5 mg/kg significantly counteracted the acute signs of intoxication and the impaired behavioral performance, attenuated some of the inflammatory response with no effect on morphological damage. Midazolam 1mg/kg showed only a slight tendency to modulate the cognitive function. In addition, the delayed administration of both midazolam doses significantly attenuated ECoG compared to TA treatment only. These results suggest that following prolonged seizure, high dose midazolam is beneficial in counteracting adverse effects of sarin poisoning.

  13. Ibuprofen administration attenuates serum TNF-{alpha} levels, hepatic glutathione depletion, hepatic apoptosis and mouse mortality after Fas stimulation

    SciTech Connect

    Cazanave, Sophie; Vadrot, Nathalie; Tinel, Marina; Berson, Alain; Letteron, Philippe; Larosche, Isabelle; Descatoire, Veronique; Feldmann, Gerard; Robin, Marie-Anne |; Pessayre, Dominique |

    2008-09-15

    Fas stimulation recruits neutrophils and activates macrophages that secrete tumor necrosis factor-{alpha} (TNF-{alpha}), which aggravates Fas-mediated liver injury. To determine whether nonsteroidal anti-inflammatory drugs modify these processes, we challenged 24-hour-fasted mice with the agonistic Jo2 anti-Fas antibody (4 {mu}g/mouse), and treated the animals 1 h later with saline or ibuprofen (250 mg/kg), a dual cyclooxygenase (COX)-1 and COX-2 inhibitor. Ibuprofen attenuated the Jo2-mediated recruitment/activation of myeloperoxidase-secreting neutrophils/macrophages in the liver, and attenuated the surge in serum TNF-{alpha}. Ibuprofen also minimized hepatic glutathione depletion, Bid truncation, caspase activation, outer mitochondrial membrane rupture, hepatocyte apoptosis and the increase in serum alanine aminotransferase (ALT) activity 5 h after Jo2 administration, to finally decrease mouse mortality at later times. The concomitant administration of pentoxifylline (decreasing TNF-{alpha} secretion) and infliximab (trapping TNF-{alpha}) likewise attenuated the Jo2-mediated increase in TNF-{alpha}, the decrease in hepatic glutathione, and the increase in serum ALT activity 5 h after Jo2 administration. The concomitant administration of the COX-1 inhibitor, SC-560 (10 mg/kg) and the COX-2 inhibitor, celecoxib (40 mg/kg) 1 h after Jo2 administration, also decreased liver injury 5 h after Jo2 administration. In contrast, SC-560 (10 mg/kg) or celecoxib (40 or 160 mg/kg) given alone had no significant protective effects. In conclusion, secondary TNF-{alpha} secretion plays an important role in Jo2-mediated glutathione depletion and liver injury. The combined inhibition of COX-1 and COX-2 by ibuprofen attenuates TNF-{alpha} secretion, glutathione depletion, mitochondrial alterations, hepatic apoptosis and mortality in Jo2-treated fasted mice.

  14. Bupropion attenuates methamphetamine self-administration in adult male rats.

    PubMed

    Reichel, Carmela M; Murray, Jennifer E; Grant, Kathleen M; Bevins, Rick A

    2009-02-01

    Bupropion is a promising candidate medication for methamphetamine use disorder. As such, we used a preclinical model of drug-taking to determine the effects of bupropion on the reinforcing effects of methamphetamine (0.025, 0.05 or 0.1 mg/kg/infusion). Specificity was determined by investigating the effects of bupropion on responding maintained by sucrose. In the self-administration study, rats were surgically prepared with indwelling jugular catheters and trained to self-administer methamphetamine under an FR5 schedule. A separate group of rats was trained to press a lever for sucrose. Once responding stabilized, rats were pretreated with bupropion (0, 10, 30 and 60 mg/kg i.p.) 5 min before chamber placement in a unique testing order. Following acute testing, rats were then repeatedly pretreated with 30 and 60 mg/kg bupropion. Acute treatments of bupropion dose dependently reduced drug intake for 0.025-0.1 mg/kg methamphetamine; sucrose deliveries were only reduced with the high bupropion dose. Repeated exposure to 60 mg/kg bupropion before the session resulted in a consistent decrease in methamphetamine intake (0.05 and 0.1 mg/kg) and sucrose deliveries. Considered together, this pattern of findings demonstrates that bupropion decreases responding for methamphetamine, but the effects are only somewhat specific.

  15. Long-term administration of fluvoxamine attenuates neuropathic pain and involvement of spinal serotonin receptors in diabetic model rats.

    PubMed

    Kato, Takahiro; Kajiyama, Seiji; Hamada, Hiroshi; Kawamoto, Masashi

    2013-12-01

    Diabetic neuropathic pain management is difficult even with non-steroidal anti-inflammatory drugs and narcotic analgesics such as morphine. Fluvoxamine, a class of selective serotonin reuptake inhibitors (SSRIs), is widely used to treat depression. Its analgesic effects are also documented for diabetic neuropathic pain, but they are limited because it is administered as a single-dose. In this study, we examined the time course of the antiallodynic effect of fluvoxamine in a rat model of diabetic neuropathic pain, which was induced by a single intraperitoneal administration of streptozotocin (75 mg/kg). In addition, the involvement of spinal serotonin (5-HT) receptors in long-term fluvoxamine treatment was studied by intrathecal administration of 5-HT receptor antagonists. In this study the development of mechanical hyperalgesia was assessed by measuring the hind paw withdrawal threshold using von Frey filaments. The results demonstrated that daily oral administration of fluvoxamine (10, 30, and 100 mg/kg) to diabetic rats from 3 to 8 weeks after streptozotocin administration resulted in a dose-dependent antiallodynic effect. The antiallodynic effect was sustained from 2 to 5 weeks after fluvoxamine administration. The antiallodynic effect of fluvoxamine in the diabetic rats was attenuated by WAY-100635 (a 5-HT(1A) receptor antagonist) intrathecally administered 1 week after the onset of daily administration of fluvoxamine, whereas no significant attenuation was seen when the antagonist was administered 3 and 5 weeks after fluvoxamine administration. The antiallodynic effect of fluvoxamine was also attenuated by ketanserin (a 5-HT(2A/2C) receptor antagonist) and ondansetron (a 5-HT3 receptor antagonist) intrathecally administered 1 and 3 weeks after the onset of daily fluvoxamine administration. However, no significant attenuation was observed when the antagonist was administered 5 weeks after fluvoxamine administration. This study demonstrated that daily oral

  16. Single administration of vildagliptin attenuates postprandial hypertriglyceridemia and endothelial dysfunction in normoglycemic individuals.

    PubMed

    Noguchi, Kaoru; Hirota, Minoru; Miyoshi, Toru; Tani, Yoshinori; Noda, Yoko; Ito, Hiroshi; Nanba, Seiji

    2015-01-01

    Postprandial hypertriglyceridemia impairs endothelial function and plays an important role in the development of atherosclerosis. The aim of the present study was to examine the postprandial effects of the dipeptidyl peptidase-4 inhibitor vildagliptin and the α-glucosidase inhibitor voglibose on endothelial dysfunction and lipid profiles following a single administration. A randomized cross-over trial using 11 normoglycemic individuals was performed. The postprandial effects of a single administration of vildagliptin (50 mg) or voglibose (0.3 mg) on endothelial function were analyzed using brachial artery flow-mediated dilation (FMD) and lipid profiles during fasting and 1.5 and 3 h after an oral cookie-loading test. Compared with voglibose, vildagliptin significantly suppressed postprandial endothelial dysfunction, (%FMD, -1.6±0.9 vildagliptin vs. -4.0±0.7 voglibose; P=0.01) and the postprandial incremental increase in the triglyceride level (28±18 vildagliptin vs. 51±26 mg/dl voglibose; P=0.01) 3 h after a cookie-loading test. In addition, vildagliptin significantly increased the levels of glucagon-like peptide-1 compared with voglibose 3 h after a loading cookie test (4.4±0.6 vs. 2.9±0.7 pmol/l, respectively; P=0.04). No significant differences in the levels of glucose, apolipoprotein B-48, glucagon or insulin were observed between vildagliptin and voglibose treatments. In conclusion, a single administration of vildagliptin attenuated postprandial endothelial dysfunction and postprandial hypertriglyceridemia, suggesting that vildagliptin may be a promising antiatherogenic agent.

  17. Oxytocin administration attenuates atherosclerosis and inflammation in Watanabe Heritable Hyperlipidemic rabbits.

    PubMed

    Szeto, Angela; Rossetti, Maria A; Mendez, Armando J; Noller, Crystal M; Herderick, Edward E; Gonzales, Julie A; Schneiderman, Neil; McCabe, Philip M

    2013-05-01

    Oxytocin (OT) is a neurohypophyseal peptide traditionally associated with female reproductive functioning, and more recently with prosocial behavior. OT and its receptor are also expressed in the heart and vascular tissue and play a role in cardiovascular homeostasis. In vitro, it has been demonstrated that OT decreases NADPH-dependent superoxide production and pro-inflammatory cytokine release from vascular endothelial cells and macrophages, suggesting that OT may attenuate pathophysiological processes involved with atherosclerotic lesion formation. The present study sought to determine the effect of chronic exogenous OT administration on inflammation and atherosclerosis in an animal model of dyslipidemia and atherosclerosis, the Watanabe Heritable Hyperlipidemic (WHHL) rabbit. Twenty-two, 3-month-old WHHLs were surgically implanted with osmotic mini-pumps containing OT (n=11) or vehicle (n=11), and then were individually housed for the entire study. Blood and 24-h urine samples were taken at baseline and after 8 (midpoint) and 16 (endpoint) weeks of treatment. At endpoint, the aortas and visceral fat samples were dissected and stored for analyses. There were no group differences in body weight, serum lipids, plasma/urinary measures of oxidative stress, plasma cortisol or urinary catecholamines over the 16-week treatment. OT-treated animals exhibited significantly lower plasma C-reactive protein levels at midpoint and endpoint and developed significantly less atherosclerosis in the thoracic aorta relative to vehicle control animals at endpoint (p<0.05). Cytokine gene expression from visceral adipose tissue samples suggested that there was a decrease in adipose tissue inflammation in the OT-treated group compared to the vehicle control group, however these differences were not statistically significant. These results suggest that chronic peripheral OT administration can inhibit inflammation and atherosclerotic lesion development.

  18. Repeated administration of an acetylcholinesterase inhibitor attenuates nicotine taking in rats and smoking behavior in human smokers.

    PubMed

    Ashare, R L; Kimmey, B A; Rupprecht, L E; Bowers, M E; Hayes, M R; Schmidt, H D

    2016-01-19

    Tobacco smoking remains the leading cause of preventable death worldwide and current smoking cessation medications have limited efficacy. Thus, there is a clear need for translational research focused on identifying novel pharmacotherapies for nicotine addiction. Our previous studies demonstrated that acute administration of an acetylcholinesterase inhibitor (AChEI) attenuates nicotine taking and seeking in rats and suggest that AChEIs could be repurposed for smoking cessation. Here, we expand upon these findings with experiments designed to determine the effects of repeated AChEI administration on voluntary nicotine taking in rats as well as smoking behavior in human smokers. Rats were trained to self-administer intravenous infusions of nicotine (0.03 mg kg(-1) per 0.59 ml) on a fixed-ratio-5 schedule of reinforcement. Once rats maintained stable nicotine taking, galantamine or donepezil was administered before 10 consecutive daily nicotine self-administration sessions. Repeated administration of 5.0 mg kg(-1) galantamine and 3.0 mg kg(-1) donepezil attenuated nicotine self-administration in rats. These effects were reinforcer-specific and not due to adverse malaise-like effects of drug treatment as repeated galantamine and donepezil administration had no effects on sucrose self-administration, ad libitum food intake and pica. The effects of repeated galantamine (versus placebo) on cigarette smoking were also tested in human treatment-seeking smokers. Two weeks of daily galantamine treatment (8.0 mg (week 1) and 16.0 mg (week 2)) significantly reduced smoking rate as well as smoking satisfaction and reward compared with placebo. This translational study indicates that repeated AChEI administration reduces nicotine reinforcement in rats and smoking behavior in humans at doses not associated with tolerance and/or adverse effects.

  19. Oral Administration of Gintonin Attenuates Cholinergic Impairments by Scopolamine, Amyloid-β Protein, and Mouse Model of Alzheimer's Disease.

    PubMed

    Kim, Hyeon-Joong; Shin, Eun-Joo; Lee, Byung-Hwan; Choi, Sun-Hye; Jung, Seok-Won; Cho, Ik-Hyun; Hwang, Sung-Hee; Kim, Joon Yong; Han, Jung-Soo; Chung, ChiHye; Jang, Choon-Gon; Rhim, Hyewon; Kim, Hyoung-Chun; Nah, Seung-Yeol

    2015-09-01

    Gintonin is a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand. Oral administration of gintonin ameliorates learning and memory dysfunctions in Alzheimer's disease (AD) animal models. The brain cholinergic system plays a key role in cognitive functions. The brains of AD patients show a reduction in acetylcholine concentration caused by cholinergic system impairments. However, little is known about the role of LPA in the cholinergic system. In this study, we used gintonin to investigate the effect of LPA receptor activation on the cholinergic system in vitro and in vivo using wild-type and AD animal models. Gintonin induced [Ca(2+)]i transient in cultured mouse hippocampal neural progenitor cells (NPCs). Gintonin-mediated [Ca(2+)]i transients were linked to stimulation of acetylcholine release through LPA receptor activation. Oral administration of gintonin-enriched fraction (25, 50, or 100 mg/kg, 3 weeks) significantly attenuated scopolamine-induced memory impairment. Oral administration of gintonin (25 or 50 mg/kg, 2 weeks) also significantly attenuated amyloid-β protein (Aβ)-induced cholinergic dysfunctions, such as decreased acetylcholine concentration, decreased choline acetyltransferase (ChAT) activity and immunoreactivity, and increased acetylcholine esterase (AChE) activity. In a transgenic AD mouse model, long-term oral administration of gintonin (25 or 50 mg/kg, 3 months) also attenuated AD-related cholinergic impairments. In this study, we showed that activation of G protein-coupled LPA receptors by gintonin is coupled to the regulation of cholinergic functions. Furthermore, this study showed that gintonin could be a novel agent for the restoration of cholinergic system damages due to Aβ and could be utilized for AD prevention or therapy.

  20. Nicotine administration in the wake-promoting basal forebrain attenuates sleep-promoting effects of alcohol.

    PubMed

    Sharma, Rishi; Lodhi, Shafi; Sahota, Pradeep; Thakkar, Mahesh M

    2015-10-01

    Nicotine and alcohol co-abuse is highly prevalent, although the underlying causes are unclear. It has been suggested that nicotine enhances pleasurable effects of alcohol while reducing aversive effects. Recently, we reported that nicotine acts via the basal forebrain (BF) to activate nucleus accumbens and increase alcohol consumption. Does nicotine suppress alcohol-induced aversive effects via the BF? We hypothesized that nicotine may act via the BF to suppress sleep-promoting effects of alcohol. To test this hypothesis, adult male Sprague-Dawley rats were implanted with sleep-recording electrodes and bilateral guides targeted toward the BF. Nicotine (75 pmol/500 nL/side) or artificial cerebrospinal fluid (ACSF; 500 nL/side) was microinjected into the BF followed by intragastric alcohol (ACSF + EtOH and NiC + EtOH groups; 3 g/kg) or water (NiC + W and ACSF + W groups; 10 mL/kg) administration. On completion, rats were killed and processed to localize injection sites in the BF. The statistical analysis revealed a significant effect of treatment on sleep-wakefulness. While rats exposed to alcohol (ACSF + EtOH) displayed strong sleep promotion, nicotine pre-treatment in the BF (NiC + EtOH) attenuated alcohol-induced sleep and normalized sleep-wakefulness. These results suggest that nicotine acts via the BF to suppress the aversive, sleep-promoting effects of alcohol, further supporting the role of BF in alcohol-nicotine co-use.

  1. Oral administration of Enterococcus faecalis FK-23 suppresses Th17 cell development and attenuates allergic airway responses in mice.

    PubMed

    Zhang, Bei; An, Jun; Shimada, Takashi; Liu, Shuang; Maeyama, Kazutaka

    2012-08-01

    Evidence is increasing that oral administration of probiotics can attenuate asthmatic responses both in murine models and clinical trials. T-helper 17 (Th17) cells, a subset of CD4+ T cells have been implicated as having an important role in the development of several allergic disorders, but the relationship between oral administration of probiotics and Th17 development has not been well studied. BALB/c mice were given lysed Enterococcus faecalis FK-23 (LFK) orally for 28 days. After sensitization by subcutaneous injection of ovalbumin (OVA) on Days 14 and 21 and 1% OVA inhalation on Days 25, 26 and 27, they were challenged with a 5% OVA aerosol on Day 28. Twenty-four hours later, airway resistance and accumulation of inflammatory cells in bronchoalveolar lavage fluid (BALF) and lung tissues were determined. Ιnterleukin (IL)-17-expressing CD4+ lymphocytes isolated from lung, spleen and lamina propria of the intestine were detected by flow cytometry. The expression of IL-6 and TGF-β mRNA was assessed by real-time PCR. Increases in airway hyperresponsiveness, and numbers of total leukocytes and mast cells in BALF induced by OVA challenge were significantly suppressed by oral administration of LFK. The increased percentage of IL-17-expressing CD4+ cells from lung, spleen and intestine in OVA-challenged mice was reduced following LFK treatment. We conclude that the oral administration of LFK suppresses the asthmatic response and that this is associated with attenuation of Th17 cell development.

  2. Prior methamphetamine self-administration attenuates the dopaminergic deficits caused by a subsequent methamphetamine exposure.

    PubMed

    McFadden, Lisa M; Vieira-Brock, Paula L; Hanson, Glen R; Fleckenstein, Annette E

    2015-06-01

    Others and we have reported that prior methamphetamine (METH) exposure attenuates the persistent striatal dopaminergic deficits caused by a subsequent high-dose "binge" METH exposure. The current study investigated intermediate neurochemical changes that may contribute to, or serve to predict, this resistance. Rats self-administered METH or saline for 7 d. On the following day (specifically, 16 h after the conclusion of the final METH self-administration session), rats received a binge exposure of METH or saline (so as to assess the impact of prior METH self-administration), or were sacrificed without a subsequent METH exposure (i.e., to assess the status of the rats at what would have been the initiation of the binge METH treatment). Results revealed that METH self-administration per se decreased striatal dopamine (DA) transporter (DAT) function and DA content, as assessed 16 h after the last self-administration session. Exposure to a binge METH treatment beginning at this 16-h time point decreased DAT function and DA content as assessed 1 h after the binge METH exposure: this effect on DA content (but not DAT function) was attenuated if rats previously self-administered METH. In contrast, 24 h after the binge METH treatment prior METH self-administration: 1) attenuated deficits in DA content, DAT function and vesicular monoamine transporter-2 function; and 2) prevented increases in glial fibrillary acidic protein and DAT complex immunoreactivity. These data suggest that changes 24 h, but not 1 h, after binge METH exposure are predictive of tolerance against the persistence of neurotoxic changes following binge METH exposures.

  3. Attenuation of methylphenidate-induced tolerance on cognition by buspirone co-administration.

    PubMed

    Alam, Nausheen; Najam, Rahila; Khan, Saira Saeed

    2015-09-01

    Methylphenidate as a psycho stimulant drug has been prescribed in neuropsychiatric disorders to increase cognition and attention therefore is a medication of choice for attention-deficit/hyperactivity disorder however long-term administration of central nervous system stimulant produces tolerance on cognitive behavior. Previously it has been shown that long-term psychostimulant administration increases somatodendritic 5HT-1A receptors effectiveness. Repeated buspirone administration attenuates 5-HT1A soma to dendritic receptors effectiveness. This study was designed to determine that buspirone co-administration may reduce methylphenidate-induced tolerance on cognitive behavior. Cognitive effects were compared by using water maze and passive avoidance test weekly after long-term administration of methylphenidate, buspirone and their co-administration. Methylphenidate at a dose of 2.0mg/kg/day in rats initially improve memory but after long-term treatment produce tolerance on cognitive behavior this effect is more pronounce in case of spatial working memory of water maze test than passive avoidance learning memory. However oral buspirone co-administration at a dose of 10mg/kg/day prevents methylphenidate-induce tolerance on cognition. It is suggested that buspirone may oppose methylphenidate-induced cognitive tolerance by reducing the sensitivity of 5-HT 1A soma to dendritic receptors. These findings may help to extend future therapeutics in ADHD.

  4. Inhibition of histone deacetylases facilitates extinction and attenuates reinstatement of nicotine self-administration in rats.

    PubMed

    Castino, Matthew R; Cornish, Jennifer L; Clemens, Kelly J

    2015-01-01

    Chromatin remodelling is integral to the formation of long-term memories. Recent evidence suggests that histone modification may play a role in the persistence of memories associated with drug use. The present series of experiments aimed to examine the effect of histone deacetylase (HDAC) inhibition on the extinction and reinstatement of nicotine self-administration. Rats were trained to intravenously self-administer nicotine for 12 days on a fixed-ratio 1 schedule. In Experiment 1, responding was then extinguished through removal of nicotine and response-contingent cues. After each extinction session, the HDAC inhibitor, sodium butyrate (NaB), was administered immediately, or six hours after each session. In Experiment 2, response-contingent cues remained available across extinction to increase rates of responding during this phase, and NaB was administered immediately after the session. Finally, in Experiment 3, the effect of NaB treatment on extinction of responding for sucrose pellets was assessed. Across all experiments reinstatement to the cue and/or the reward itself was then tested. In the first experiment, treatment with NaB significantly attenuated nicotine and nicotine + cue reinstatement when administered immediately, but not six hours after each extinction session. When administered after cue-extinction (Expt. 2), NaB treatment specifically facilitated the rate of extinction across sessions, indicating that HDAC inhibition enhanced consolidation of the extinction memory. In contrast, there was no effect of NaB on the extinction and reinstatement of sucrose-seeking (Expt. 3), indicating that the observed effects are specific to a drug context. These results provide the first demonstration that HDAC inhibition facilitates the extinction of responding for an intravenously self-administered drug of abuse and further highlight the potential of HDAC inhibitors in the treatment of drug addiction.

  5. Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice

    PubMed Central

    Kukar, Thomas; Prescott, Sonya; Eriksen, Jason L; Holloway, Vallie; Murphy, M Paul; Koo, Edward H; Golde, Todd E; Nicolle, Michelle M

    2007-01-01

    Background Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Aβ42 in cell culture and animal models, and that the effect of NSAIDs on Aβ42 is independent of the inhibition of cyclooxygenase by these compounds. Since Aβ42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Aβ42 selectively may be associated with their protective effect. We have previously identified R-flurbiprofen (tarenflurbil) as a selective Aβ42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic R-flurbiprofen treatment on cognition and Aβ loads in Tg2576 APP mice. Results A four-month preventative treatment regimen with R-flurbiprofen (10 mg/kg/day) was administered to young Tg2576 mice prior to robust plaque or Aβ pathology. This treatment regimen improved spatial learning as assessed by the Morris water maze, indicated by an increased spatial bias during the third probe trial and an increased utilization of a place strategy to solve the water maze. These results are consistent with an improvement in hippocampal- and medial temporal lobe-dependent memory function. A modest, though not statistically significant, reduction in formic acid-soluble levels of Aβ was also observed. To determine if R-flurbiprofen could reverse cognitive deficits in Tg2576 mice where plaque pathology was already robust, a two-week therapeutic treatment was given to older Tg2576 mice with the same dose of R-flurbiprofen. This approach resulted in a significant decrease in Aβ plaque burden but no significant improvement in spatial learning. Conclusion We have found that chronic administration of R-flurbiprofen is able to attenuate spatial learning deficits if given prior to plaque deposition in Tg2576 mice. Given its

  6. Parenteral administration of attenuated Salmonella Typhimurium ΔznuABC is protective against salmonellosis in piglets.

    PubMed

    Ruggeri, J; Pesciaroli, M; Gaetarelli, B; Scaglione, F E; Pregel, P; Ammendola, S; Battistoni, A; Bollo, E; Alborali, G L; Pasquali, P

    2014-07-07

    A major cause of salmonellosis in humans is the contamination of pork products. Infection in pigs can be controlled using bio-security programs, but they are not sufficient in countries where a high level of infection is recorded. In this context, the use of vaccines can represent a valid supplementary method of control. Recently, we have demonstrated that an attenuated strain of Salmonella enterica serovar Typhimurium (Salmonella Typhimurium ΔznuABC) is protective against systemic and enteric salmonellosis in mouse and pig infection models, candidating this strain as an oral attenuated vaccine. In this study, we compared the efficacy of this attenuated Salmonella Typhimurium strain when administered orally or parenterally. Furthermore, in order to reproduce a pseudo-natural infection model, vaccinated pigs were allocated in the same pen with animals shedding virulent Salmonella Typhimurium. Animals were monitored weekly after vaccination and contact with infected piglets. Diarrhea and ataxia were recorded and Salmonella shedding was tested individually through bacterial culture. After four weeks of cohousing, piglets were euthanized, after which lymph nodes reactivity and gross lesions of the gut sections were scored at necropsy. Organs were submitted to microbiological and histological analyses. The data reported herein show that parenterally vaccinated animals do not shed the attenuated strain, and at the same time the absence of symptoms and decrease in virulent strain shedding in feces from day 6 after challenge demonstrated protection against infection induced by virulent Salmonella Typhimurium. In conclusion, our findings suggest that this is an alternative route of Salmonella Typhimurium ΔznuABC administration, without ignoring the advantages associated with oral vaccination.

  7. Methamphetamine self-administration attenuates hippocampal serotonergic deficits: Role of brain derived neurotrophic factor

    PubMed Central

    McFadden, Lisa M.; Vieira-Brock, Paula L.; Hanson, Glen R.; Fleckenstein, Annette E.

    2014-01-01

    Preclinical studies suggest that prior treatment with escalating doses of methamphetamine (METH) attenuates the persistent deficits in hippocampal serotonin (5-hydroxytryptamine; 5HT) transporter (SERT) function resulting from a subsequent “binge” METH exposure. Previous work also demonstrates that brain derived neurotrophic factor (BDNF) exposure increases SERT function. The current study investigated changes in hippocampal BDNF protein and SERT function in rats exposed to saline or METH self-administration prior to a binge exposure to METH or saline. Results revealed that METH self-administration increased hippocampal mature BDNF (mBDNF) immunoreactivity compared to saline-treated rats as assessed 24 h after the start of the last session. Further, mBDNF immunoreactivity was increased and SERT function was not altered at this timepoint in rats that self-administered METH prior to the binge METH exposure. These results suggest that prior exposure to contingent METH increases hippocampal mBDNF, and this may contribute to attenuated deficits in SERT function. PMID:24650575

  8. Attenuation of methylphenidate-induced sensitization by co-administration of buspirone.

    PubMed

    Alam, Nausheen; Najam, Rahila; Naeem, Sadaf

    2016-03-01

    Methylphenidate, which inhibit dopamine transporter is effective in the treatment of ADHD (attention deficit hyperactivity disorder), but long term use of this drug is often associated with addiction and dependence. Locomotor sensitization development to psychostimulants like methylphenidate is an important contributor to drug abuse induced by psychostimulants. Different studies have shown that long term administration of drugs of abuse increases the effectiveness of 5-hydroxytryptamine (5-HT)-1A somatodendritic receptors. Repeated buspirone administration reduces the effectiveness of 5-HT1A somatodendritic receptors. This study was designed to determine that buspirone co-administration may reduce methylphenidate-induced sensitization. The motor activity was compared by using familiar and novel environments after long-term administration of methylphenidate, buspirone and their co-administration. Long term oral administration of methylphenidate at a dose of 2.0 mg/kg/day enhanced motor activity in home cage i.e. activity of familiar environment monitored at alternate day. Locomotor enhancing effects of methylphenidate were augmented on 13th day of drug administration suggesting sensitization induced by the drug. The sensitization effects were significant in home cage monitored on alternate day and also in an open field monitored weekly. Buspirone co-administration at a dose of 10 mg/kg/day prevented methylphenidate-induced sensitization. It is suggested that the sensitization development to methylphenidate may oppose by buspirone co-administration due to the reduction in the sensitivity of 5-HT1A somatodendritic receptors. These findings may help extend future therapeutics in ADHD.

  9. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L.; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

    2015-12-01

    Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies.

  10. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation.

    PubMed

    Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

    2015-12-01

    Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies.

  11. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

    PubMed Central

    Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L.; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

    2016-01-01

    Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies. PMID:26587712

  12. Immunomodulaton and attenuation of lethal influenza A virus infection by oral administration with KIOM-C.

    PubMed

    Kim, Eun-Ha; Pascua, Philippe Noriel Q; Song, Min-Suk; Baek, Yun Hee; Kwon, Hyeok-Il; Park, Su-Jin; Lim, Gyo-Jin; Kim, Se Mi; Decano, Arun; Lee, Kwang Jin; Cho, Won-Kyung; Ma, Jin Yeul; Choi, Young Ki

    2013-06-01

    Herbal medicine is used to treat many conditions such as asthma, eczema, premenstrual syndrome, rheumatoid arthritis, migraine, headaches, menopausal symptoms, chronic fatigue, irritable bowel syndrome, cancer, and viral infections such as influenza. In this study, we investigated the antiviral effect of KIOM-C for the treatment of influenza A virus infection. Our results show that oral administration of KIOM-C conferred a survival benefit to mice infected with the 2009 pandemic H1N1 [A(H1N1)pdm09] virus, and resulted in a 10- to 100-fold attenuation of viral replication in ferrets in a dose-dependent manner. Additionally, oral administration of KIOM-C increased the production of antiviral cytokines, including IFN-γ and TNF-α, and decreased levels of pro-inflammatory cytokines (IL-6) and chemokines (KC, MCP-1) in the Bronchoalveolar lavage fluid (BALF) of A(H1N1)pdm-infected mice. These results indicate that KIOM-C can promote clearance of influenza virus in the respiratory tracts of mice and ferrets by modulating cytokine production in hosts. Taken together, our results suggest that KIOM-C is a potential therapeutic compound mixture for the treatment of influenza virus infection in humans.

  13. Oral administration of Lactobacillus plantarum lysates attenuates the development of atopic dermatitis lesions in mouse models.

    PubMed

    Kim, Hangeun; Kim, Hye Rim; Kim, Na-Ra; Jeong, Bong Jun; Lee, Jong Suk; Jang, Soojin; Chung, Dae Kyun

    2015-01-01

    Lactobacillus plantarum is a well-documented probiotic that has been used in clinical trials for the regulation of the immune system and treatment of gastrointestinal diseases. In this study, we evaluated the effects of L. plantarum cell lysates on the immune regulation through the in vitro and in vivo studies. L. plantarum lysates were prepared by sonication method, and we observed that the repetition of disruption step increased indicator components within the bacterial lysates. Indicator components might affect TNF-α production. L. plantarum lysates did not induce TNF-α production, while LPS-induced TNF-α production was dramatically inhibited in a sonication-dependent manner in THP-1 cells. Oral administration of L. plantarum lysates effectively attenuated the horny layer formation and decreased epidermal thickening in NC/Nga mice skin. The damage to barrier function after the 8 weeks oral administration was reduced by L. plantarum lysates as compared to that in the atopic dermatitis (AD) mice. Further study revealed that L. plantarum lysates polarized Th1 response via induction of IL-12 and IFN-γ production and inhibition of IL-4 and IgE production in NC/Nga mice. Together, our results suggest that L. plantarum lysates are remarkable material for host homeostasis and it could be used for the treatment of inflammatory diseases.

  14. Systemic administration of vitamins C and E attenuates nociception induced by chronic constriction injury of the sciatic nerve in rats.

    PubMed

    Riffel, Ana Paula K; de Souza, Jéssica A; Santos, Maria do Carmo Q; Horst, Andréa; Scheid, Taína; Kolberg, Carolina; Belló-Klein, Adriane; Partata, Wania A

    2016-03-01

    Antioxidants have been tested to treat neuropathic pain, and α-Tocopherol (vitamin E--vit. E) and ascorbic acid (vitamin C--vit. C) are potent antioxidants. We assessed the effect of intraperitoneal administration of vit. C (30 mg/kg/day) and vit. E (15 mg/kg/day), given alone or in combination, on the mechanical and thermal thresholds and the sciatic functional index (SFI) in rats with chronic constriction injury (CCI) of the sciatic nerve. We also determined the lipid hydroperoxides and total antioxidant capacity (TAC) in the injured sciatic nerve. Further, we assessed the effects of oral administration of vit. C+vit. E (vit. C+E) and of a combination of vit. C+E and gabapentin (100mg/kg/day, i.p.) on the mechanical and thermal thresholds of CCI rats. The vitamins, whether administered orally or i.p., attenuated the reductions in the mechanical and thermal thresholds induced by CCI. The antinociceptive effect was greater with a combination of vit. C+E than with each vitamin given alone. The SFI was also improved in vitamin-treated CCI rats. Co-administration of vit. C+E and gabapentin induced a greater antinociceptive effect than gabapentin alone. No significant change occurred in TAC and lipid hydroperoxide levels, but TAC increased (45%) while lipid hydroperoxides decreased (38%) in the sciatic nerve from vit. C+E-treated CCI rats. Thus, treatment with a combination of vit. C+E was more effective to treat CCI-induced neuropathic pain than vitamins alone, and the antinociceptive effect was greater with co-administration of vit. C+E and gabapentin than with gabapentin alone.

  15. Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration.

    PubMed

    McFadden, Lisa M; Hoonakker, Amanda J; Vieira-Brock, Paula L; Stout, Kristen A; Sawada, Nicole M; Ellis, Jonathan D; Allen, Scott C; Walters, Elliot T; Nielsen, Shannon M; Gibb, James W; Alburges, Mario E; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2011-08-01

    Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent [i.e., postnatal day (PND) 40] rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a "challenge" high-dose METH regimen when administered at PND90. Mechanisms underlying this "resistance" were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH during development. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity.

  16. Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration

    PubMed Central

    McFadden, Lisa M; Hoonakker, Amanda J; Vieira-Brock, Paula L; Stout, Kristen A; Sawada, Nicole M; Ellis, Jonathan D; Allen, Scott C; Walters, Elliot T; Nielsen, Shannon M; Gibb, James W; Alburges, Mario E; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2013-01-01

    Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent (i.e., postnatal day (PND) 40) rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a “challenge” high-dose METH regimen when administered at PND90. Mechanisms underlying this “resistance” were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH during development. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity. PMID:21190217

  17. Co-administration of attenuated Mycoplasma hyopneumoniae 168 strain with bacterial DNA enhances the local and systemic immune response after intranasal vaccination in pigs.

    PubMed

    Li, Yunfeng; Li, Pengcheng; Wang, Xueping; Yu, Qinghua; Yang, Qian

    2012-03-09

    Mycoplasma hyopneumoniae, the primary pathogen of enzootic pneumonia, occurs worldwide and causes major economic losses to the pig industry. M. hyopneumoniae infects pigs at mucosal surfaces of respiratory tract. The aim of the present study was to investigate if the protection rate against M. hyopneumoniae infection following intranasal immunization with attenuated M. hyopneumoniae 168 strain is improved by administration of bacterial DNA containing CpG motifs. Thirty pigs were immunized intranasally or intramuscularly and the levels of local respiratory tract and systemic immune responses were detected. The results showed that the number of intraepithelial lymphocytes in the tracheal fork, the levels of cytokine IL-6, and M. hyopneumoniae specific SIgA in local nasal cavity increased respectively after intranasal vaccination with the attenuated M. hyopneumoniae 168 strain alone. However, the levels of IL-10 and IFN-γ in local nasal cavity, the number of intraepithelial lymphocytes in trachea, CD4(+) and CD8(+) T lymphocytes in the lung and hilar lymph nodes, the specific IgG antibody level in serum on 35 day post immunization were all increased significantly after intranasal vaccination of the attenuated M. hyopneumoniae 168 strain adjuvanted with bacterial DNA. We concluded that intranasal administration of attenuated M. hyopneumoniae 168 strain adjuvanted with bacterial DNA may be effective in evoking the local cellular and humoral immune response in the respiratory tract and the systemic immune response. Intranasal vaccination will be effective in prevention of the transmission and prevalence of MPS.

  18. The administration of Fructus Schisandrae attenuates dexamethasone-induced muscle atrophy in mice

    PubMed Central

    KIM, JOO WAN; KU, SAE-KWANG; HAN, MIN HO; KIM, KI YOUNG; KIM, SUNG GOO; KIM, GI-YOUNG; HWANG, HYE JIN; KIM, BYUNG WOO; KIM, CHEOL MIN; CHOI, YUNG HYUN

    2015-01-01

    In the present study, we aimed to determine whether ethanol extracts of Fructus Schisandrae (FS), the dried fruit of Schizandra chinensis Baillon, mitigates the development of dexamethasone-induced muscle atrophy. Adult SPF/VAT outbred CrljOri:CD1 (ICR) mice were either treated with dexamethasone to induce muscle atrophy. Some mice were treated with various concentrations of FS or oxymetholone, a 17α-alkylated anabolic-androgenic steroid. Muscle thickness and weight, calf muscle strength, and serum creatine and creatine kinase (CK) levels were then measured. The administration of FS attenuated the decrease in calf thickness, gastrocnemius muscle thickness, muscle strength and weight, fiber diameter and serum lactate dehydrogenase levels in the gastrocnemius muscle bundles which was induced by dexamethasone in a dose-dependent manner. Treatment with FS also prevented the dexamethasone-induced increase in serum creatine and creatine kinase levels, histopathological muscle fiber microvacuolation and fibrosis, and the immunoreactivity of muscle fibers for nitrotyrosine, 4-hydroxynonenal, inducible nitric oxide synthase and myostatin. In addition, the destruction of the gastrocnemius antioxidant defense system was also inhibited by the administration of FS in a dose-dependent manner. FS downregulated the mRNA expression of atrogin-1 and muscle RING-finger protein-1 (involved in muscle protein degradation), myostatin (a potent negative regulator of muscle growth) and sirtuin 1 (a representative inhibitor of muscle regeneration), but upregulated the mRNA expression of phosphatidylinositol 3-kinase, Akt1, adenosine A1 receptor and transient receptor potential cation channel subfamily V member 4, involved in muscle growth and the activation of protein synthesis. The overall effects of treatment with 500 mg/kg FS were comparable to those observed following treatment with 50 mg/kg oxymetholone. The results from the present study support the hypothesis that FS has a favorable

  19. Live attenuated Salmonella displaying HIV-1 10E8 epitope on fimbriae: systemic and mucosal immune responses in BALB/c mice by mucosal administration

    PubMed Central

    Li, Qing-Hai; Jin, Gang; Wang, Jia-Ye; Li, Hai-Ning; Liu, Huidi; Chang, Xiao-Yun; Wang, Fu-Xiang; Liu, Shu-Lin

    2016-01-01

    The HIV-1 membrane proximal external region (MPER) that is targeted by several broadly neutralizing antibodies (BNAbs) has been considered a potential immunogen for vaccine development. However, to date the immunogenicity of these BNAb epitopes has not been made sufficiently adequate. In the present work, we used live attenuated Salmonella as a platform to present the HIV-1 MPER 10E8 epitope in the fimbriae. The insertion of the 10E8 epitope into the fimbriae had no significant influence on the expression and the absorption capacity of bacterial fimbriae, nor on the virulence and invasiveness of the attenuated Salmonella. After oral administration of the vaccine construct to mice followed by 10E8 epitope peptide boost, specific antibody responses in serum and mucosa as well as memory lymphocytes in spleen and plasma cells in bone marrow were induced. We also found that the live attenuated Salmonella vector directed the immunity toward Th1 bias, induced Th1 and Th2 cytokine responses and stimulated significant B cell differentiation into GC B, memory B and plasma cells. Therefore, we propose that the live attenuated Salmonella constitutively expressing HIV-1 BNAb epitopes on the fimbriae will be an effective approach to improving immune microenvironment and enhancing the immunogenicity of HIV-1 epitope vaccines. PMID:27411313

  20. Oral L-glutamine administration attenuated cutaneous wound healing in Wistar rats.

    PubMed

    Goswami, Saurabh; Kandhare, Amit; Zanwar, Anand A; Hegde, Mahabaleshwar V; Bodhankar, Subhash L; Shinde, Sudhir; Deshmukh, Shahaji; Kharat, Ravindran

    2016-02-01

    The objective of this study was to evaluate the wound healing potential of L-glutamine in laboratory rats using excision and incision wound models. Excision wounds of size 500 mm(2) and depth 2 mm were made on the dorsal portion of male Wistar rats (230-250 g) and were used for the study of oral L-glutamine (1 g/kg) treatment on the rate of contraction of wound and epithelisation. Histological evaluation of wound tissue was also performed. Six-centimetre-long two linear-paravertebral incisions in male Wistar rats (230-250 g) were used to study the effect of L-glutamine (1 g/kg, p.o.) treatment on tensile strength, total protein and hydroxyproline content in the incision model. Oral administration of L-glutamine (1 g/kg) significantly decreased wound area, epithelisation period and wound index, whereas the rate of wound contraction significantly increased (P < 0·001) when compared with vehicle control rats in the excision wound model. Tensile strength, hydroxyproline content and protein level were significantly increased (P < 0·001) in L-glutamine (1 g/kg, p.o.)-treated rats when compared with vehicle control rats in the incision wound model. Histological evaluation of wound tissue from L-glutamine (1 g/kg, p.o.)-treated rats showed complete epithelialisation with new blood vessel formation and high fibrous tissues in the excision wound model. In conclusion, oral administration of l-glutamine (1 g/kg) promotes wound healing by acting on various stages of wound healing such as collagen synthesis, wound contraction and epithelialisation.

  1. Annual committee reports on significant legislative, judicial, and administrative developments in 1981: Environmental-Quality Committee

    SciTech Connect

    Not Available

    1982-01-01

    The committee found significant developments under the National Environmental Policy Act (NEPA). There were no amendments to NEPA, but there were new rules affecting DOE defense-related nuclear facilities. Judicial developments continued a deference to agency discretion in environmental impact statement issues and conflicts with other laws. The administration's budget cuts effectively disabled the Council on Environmental Quality (CEQ). The report also outlines significant legislative, judicial, and administrative developments for the Federal Insecticide, Fungicide, and Rodenticide Act, the Endangered Species Act, and the Toxic Substances Act. 188 references. (DCK)

  2. Critical timing, location and duration of glucocorticoid administration rescue mice from superantigen-induced shock and attenuate lung injury.

    PubMed

    Krakauer, Teresa; Buckley, Marilyn J; Huzella, Louis M; Alves, Derron A

    2009-09-01

    Bacterial superantigens, such as staphylococcal enterotoxin B (SEB), are major virulence factors implicated in the pathogenesis of toxic shock. In this study we investigated the efficacy of glucocorticoid therapy in preventing SEB-induced lethal shock initiated through the respiratory route in mice. Dexamethasone, a potent anti-inflammatory steroid, administrated intranasally on the first day, followed by intraperitoneal doses on the subsequent 4 days, was effective in attenuating SEB-induced hypothermia, and reduction in systemic and pulmonary proinflammatory mediator release. This optimal dosing and schedule of glucocorticoid treatment mitigated lung inflammation and resulted in 100% survival in this intranasal mouse model of SEB-mediated shock.

  3. Absence of an Immune Response after Oral Administration of Attenuated Feline Panleukopenia Virus

    PubMed Central

    Schultz, Ronald D.; Scott, Fredric W.

    1973-01-01

    Cats were orally vaccinated with attenuated feline panleukopenia virus to compare this route with parenteral immunization. Cats receiving vaccine virus by mouth did not produce a systemic or local antibody response to the virus. Intranasal and subcutaneous vaccination produced high levels of neutralizing antibodies and provided protection from challenge with virulent virus. The results suggest that virus does not initially infect the tissue of the oral pharynx or gastrointestinal tract as previously suspected. PMID:4762109

  4. Attenuation of cocaine self-administration by chronic oral phendimetrazine in rhesus monkeys.

    PubMed

    Czoty, P W; Blough, B E; Fennell, T R; Snyder, R W; Nader, M A

    2016-06-02

    Chronic treatment with the monoamine releaser d-amphetamine has been consistently shown to decrease cocaine self-administration in laboratory studies and clinical trials. However, the abuse potential of d-amphetamine is an obstacle to widespread clinical use. Approaches are needed that exploit the efficacy of the agonist approach but avoid the abuse potential associated with dopamine releasers. The present study assessed the effectiveness of chronic oral administration of phendimetrazine (PDM), a pro-drug for the monoamine releaser phenmetrazine (PM), to decrease cocaine self-administration in four rhesus monkeys. Each day, monkeys pressed a lever to receive food pellets under a 50-response fixed-ratio (FR) schedule of reinforcement and self-administered cocaine (0.003-0.56 mg/kg per injection, i.v.) under a progressive-ratio (PR) schedule in the evening. After completing a cocaine self-administration dose-response curve, sessions were suspended and PDM was administered (1.0-9.0 mg/kg, p.o., b.i.d.). Cocaine self-administration was assessed using the PR schedule once every 7 days while food-maintained responding was studied daily. When a persistent decrease in self-administration was observed, the cocaine dose-effect curve was re-determined. Daily PDM treatment decreased cocaine self-administration by 30-90% across monkeys for at least 4 weeks. In two monkeys, effects were completely selective for cocaine. Tolerance developed to initial decreases in food-maintained responding in the third monkey and in the fourth subject, fluctuations were observed that were lower in magnitude than effects on cocaine self-administration. Cocaine dose-effect curves were shifted down and/or rightward in three monkeys. These data provide further support for the use of agonist medications for cocaine abuse, and indicate that the promising effects of d-amphetamine extend to a more clinically viable pharmacotherapy.

  5. Short-term pyrrolidine dithiocarbamate administration attenuates cachexia-induced alterations to muscle and liver in ApcMin/+ mice

    PubMed Central

    VanderVeen, Brandon N.; Enos, Reilly T.; Murphy, E. Angela; Carson, James A.

    2016-01-01

    Cancer cachexia is a complex wasting condition characterized by chronic inflammation, disrupted energy metabolism, and severe muscle wasting. While evidence in pre-clinical cancer cachexia models have determined that different systemic inflammatory inhibitors can attenuate several characteristics of cachexia, there is a limited understanding of their effects after cachexia has developed, and whether short-term administration is sufficient to reverse cachexia-induced signaling in distinctive target tissues. Pyrrolidine dithiocarbamate (PDTC) is a thiol compound having anti-inflammatory and antioxidant properties which can inhibit STAT3 and nuclear factor κB (NF-κB) signaling in mice. This study examined the effect of short-term PDTC administration to ApcMin/+ mice on cachexia-induced disruption of skeletal muscle protein turnover and liver metabolic function. At 16 weeks of age ApcMin/+ mice initiating cachexia (7% BW loss) were administered PDTC (10mg/kg bw/d) for 2 weeks. Control ApcMin/+ mice continued to lose body weight during the treatment period, while mice receiving PDTC had no further body weight decrease. PDTC had no effect on either intestinal tumor burden or circulating IL-6. In muscle, PDTC rescued signaling disrupting protein turnover regulation. PDTC suppressed the cachexia induction of STAT3, increased mTORC1 signaling and protein synthesis, and suppressed the induction of Atrogin-1 protein expression. Related to cachectic liver metabolic function, PDTC treatment attenuated glycogen and lipid content depletion independent to the activation of STAT3 and mTORC1 signaling. Overall, these results demonstrate short-term PDTC treatment to cachectic mice attenuated cancer-induced disruptions to muscle and liver signaling, and these changes were independent to altered tumor burden and circulating IL-6. PMID:27449092

  6. The X-ray attenuation characteristics and density of human calcaneal marrow do not change significantly during adulthood

    NASA Technical Reports Server (NTRS)

    Les, C. M.; Whalen, R. T.; Beaupre, G. S.; Yan, C. H.; Cleek, T. M.; Wills, J. S.

    2002-01-01

    Changes in the material characteristics of bone marrow with aging can be a significant source of error in measurements of bone density when using X-ray and ultrasound imaging modalities. In the context of computed tomography, dual-energy computed techniques have been used to correct for changes in marrow composition. However, dual-energy quantitative computed tomography (DE-QCT) protocols, while increasing the accuracy of the measurement, reduce the precision and increase the radiation dose to the patient in comparison to single-energy quantitative computed tomography (SE-QCT) protocols. If the attenuation properties of the marrow for a particular bone can be shown to be relatively constant with age, it should be possible to use single-energy techniques without experiencing errors caused by unknown marrow composition. Marrow was extracted by centrifugation from 10 mm thick frontal sections of 34 adult cadaver calcanei (28 males, 6 females, ages 17-65 years). The density and energy-dependent linear X-ray attenuation coefficient of each marrow sample were determined. For purposes of comparing our results, we then computed an effective CT number at two GE CT/i scan voltages (80 and 120 kVp) for each specimen. The coefficients of variation for the density, CT number at 80 kVp and CT number at 120 kVp were each less than 1%, and the parameters did not change significantly with age (p > 0.2, r2 < 0.02, power > 0.8 where the minimum acceptable r2 = 0.216). We could demonstrate no significant gender-associated differences in these relationships. These data suggest that calcaneal bone marrow X-ray attenuation properties and marrow density are essentially constant from the third through sixth decades of life.

  7. Peripheral administration of fetuin-A attenuates early cerebral ischemic injury in rats

    PubMed Central

    Wang, Haichao; Li, Wei; Zhu, Shu; Li, Jianhua; D'Amore, Jason; Ward, Mary F; Yang, Huan; Wu, Rongqian; Jahnen-Dechent, Willi; Tracey, Kevin J; Wang, Ping; Sama, Andrew E

    2010-01-01

    Cerebral ischemia-elicited inflammatory responses are driven by inflammatory mediators produced both by central (e.g., neurons and microglia) and infiltrating peripheral immune cells (e.g., macrophage/monocyte), and contribute to the evolution of tissue injury. A ubiquitous molecule, spermine, is released from injured cells, and counter-regulates release of various proinflammatory cytokines. However, the spermine-mediated anti-inflammatory activities are dependent on the availability of fetuin-A, a liver-derived negative acute-phase protein. Using an animal model of focal cerebral ischemia (i.e., permanent middle cerebral artery occlusion, MCAo), we found that levels of fetuin-A in the ischemic brain tissue were elevated in a time-dependent manner, starting between 2 and 6 h, peaking around 24 to 48 h, and returning to baseline 72 h after MCAo. When administered peripherally, exogenous fetuin-A gained entry across the BBB into the ischemic brain tissue, and dose dependently reduced brain infarct volume at 24 h after MCAo. Meanwhile, fetuin-A effectively attenuated (i) ischemia-induced HMGB1 depletion from the ischemic core; (ii) activation of centrally (e.g., microglia) and peripherally derived immune cells (e.g., macrophage/monocytes); and (iii) TNF production in ischemic brain tissue. Taken together, these experimental data suggest that fetuin-A protects against early cerebral ischemic injury partly by attenuating the brain inflammatory response. PMID:19953099

  8. Local pretreatment with the cannabinoid CB1 receptor antagonist AM251 attenuates methamphetamine intra-accumbens self-administration.

    PubMed

    Rodriguez, Jesse S; Boctor, Sherin Y; Flores, Luke C; Phelix, Clyde F; Martinez, Joe L

    2011-02-11

    The endocannabinoid system is a potential target for therapeutic intervention of substance abuse. Cannabinoid CB1 receptor antagonist decreases intravenous methamphetamine self-administration in animal models. This study examined whether the nucleus accumbens (NAcc) is a site of interaction between methamphetamine and the CB1 receptor antagonist AM251. Male Sprague-Dawley rats were trained to lever press and then were surgically implanted with a guide cannula into the right NAcc. Rats were allowed one week to recover and then AM251 (0.1 or 1.0 μg/μL) was reverse dialyzed directly into the NAcc prior to methamphetamine (10 μg/μL) intra-accumbens self-administration. AM251 (1.0 μg/μL) reduced methamphetamine self-administration while AM251 (0.1 μg/μL) had an intermediary effect. The mechanism of self-administration attenuation is not known but could be mediated by AM251 affecting the negative feedback from the NAcc to the ventral tegmental area (VTA). This study provides evidence that the endocannabinoid system is involved with rewarding effects of methamphetamine and suggests a possible therapeutic intervention for methamphetamine abuse.

  9. Oral erdosteine administration attenuates cisplatin-induced renal tubular damage in rats.

    PubMed

    Yildirim, Zeki; Sogut, Sadik; Odaci, Ersan; Iraz, Mustafa; Ozyurt, Huseyin; Kotuk, Mahir; Akyol, Omer

    2003-02-01

    The effect of oral erdosteine on tissue malondialdehyde (MDA) and nitric oxide (NO) levels, and catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities are investigated in the cisplatin model of acute renal failure in rats. A single dose of cisplatin caused kidney damage manifested by kidney histology as well as increases in plasma creatinine and blood urea nitrogen (BUN) levels. Treatment with free radical scavenger erdosteine attenuated increases in plasma creatinine and BUN, and tissue MDA and NO levels, and provided a histologically-proven protection against cisplatin-induced acute renal failure. Erdosteine also reduced depletion in the tissue CAT, GSH-Px, and SOD activities. These results show that erdosteine may be a promising drug for protection against cisplatin-induced nephrotoxicity. However, further studies with different doses of erdosteine are warranted for clarifying the issue.

  10. Hepatic arterial administration of sorafenib and iodized oil effectively attenuates tumor growth and intrahepatic metastasis in rabbit VX2 hepatocellular carcinoma model

    PubMed Central

    Zhang, Lin; Liu, Feng-Yong; Fu, Jin-Xin; Duan, Feng; Fan, Qing-Sheng; Wang, Mao-Qiang

    2014-01-01

    Aim: To investigate the therapeutic effect of the hepatic arterial administration of sorafenib in rabbit VX-2 hepatocellular carcinoma (HCC) model. Methods: Rabbit VX-2 HCC models were established via implanting VX-2 tumors into the livers, and randomly divided into four groups, respectively treated with (1) The hepatic arterial administration of iodized oil alone (TACE-i), (2) The hepatic arterial administration of iodized oil and pharmorubicin (TACE-ip), (3) The hepatic arterial administration of iodized and cis-DDP (TACE-ic), (4) The hepatic arterial administration of iodized and sorafenib (TACE-is). The growth rate and intrahepatic metastasis of implanted VX-2 tumor in each rabbit were measured. Microvessel density (MVD) in the adjacent tissues of implanted VX-2 tumor were estimated by detecting the expression of CD34 and VEGF level in tumor adjacent tissues were also examined by Immunohistochemistry. Results: Compared with other groups, TACE-is treatment group presented a better effect on inhibiting tumor growth rate and intrahepatic metastasis in rabbit VX-2 HCC model. The angiogenesis (assessed by MVD) in the adjacent tissues were suppressed more dramatically in TACE-is treated group. Moreover, TACE-is treatment did not significantly increase the levels of alanine transaminase and creatinine compared to the group with TACE-i treatment. Conclusion: The hepatic arterial administration of sorafenib and iodized oil (TACE-is) effectively attenuates tumor growth and intrahepatic metastasis in rabbit VX-2 HCC model without obvious hepatic and renal toxicity. One of the related mechanisms may be due to the inhibition of angiogenesis in the adjacent tissues. Our data indicated that TACE-is may be a secure and effective treatment for HCC. PMID:25550815

  11. A calcium-insensitive attenuated nitrosative stress response contributes significantly in the radioresistance of Sf9 insect cells.

    PubMed

    Suman, Shubhankar; Seth, Rakesh Kumar; Chandna, Sudhir

    2011-09-01

    Lepidopteran insects/insect cells display 50-100 times higher radioresistance than humans, and are evolutionarily closest to mammals amongst all radioresistant organisms known. Compared to mammalian cells, Lepidopteran cells (TN-368, Sf9) display more efficient antioxidant system and DNA repair and suffer considerably less radiation-induced DNA/cytogenetic damage and apoptosis. Recent studies indicate that a considerably lower radiation-induced oxidative stress may significantly reduce macromolecular damage in Lepidopteran cells. Since nitrosative stress contributes in radiation-induced cellular damage, we investigated its nature in the γ-irradiated Sf9 cells (derived from Spodoptera frugiperda; order Lepidoptera; family Noctuidae) and compared with BMG-1 human cell line having significant NOS expression. Radiation induced considerably less ROS/RNS in Sf9 cells, which remained unchanged on treatment with NOS inhibitor l-NMMA. Surprisingly, growth of Sf9 cultures or irradiation could not induce NO or its metabolites, indicating negligible basal/radiation-induced NOS activity that remained unchanged even after supplementation with arginine. Cytosolic calcium release following high-dose (1000-2000Gy at 61.1cGys(-1)) γ-irradiation or H(2)O(2) (250μM) treatment also failed to generate NO in Sf9 cells having high constitutive levels of calmodulin, whereas BMG-1 cells displayed considerable calcium-dependent NO generation even following 10Gy dose. These results strongly imply the lack of calcium-mediated NOS activity in Sf9 cells. Addition of exogenous NO from GSH-NO caused considerable increase in radiation-induced apoptosis, indicating significant contribution of constitutively attenuated nitrosative stress response into the radioresistance of Lepidopteran cells. Our study demonstrates for the first time that a calcium-insensitive, attenuated nitrosative stress response may contribute significantly in the unusual radioresistance displayed by Lepidopteran insect cells.

  12. Antibiotic administration routes significantly influence the levels of antibiotic resistance in gut microbiota.

    PubMed

    Zhang, Lu; Huang, Ying; Zhou, Yang; Buckley, Timothy; Wang, Hua H

    2013-08-01

    This study examined the impact of oral exposure to antibiotic-resistant bacteria and antibiotic administration methods on antibiotic resistance (AR) gene pools and the profile of resistant bacteria in host gastrointestinal (GI) tracts using C57BL/6J mice with natural gut microbiota. Mice inoculated with a mixture of tet(M)-carrying Enterococcus spp. or blaCMY-2-carrying Escherichia coli were treated with different doses of tetracycline hydrochloride (Tet) or ampicillin sodium (Amp) and delivered via either feed or intravenous (i.v.) injection. Quantitative PCR assessment of mouse fecal samples revealed that (i) AR gene pools were below the detection limit in mice without prior inoculation of AR gene carriers regardless of subsequent exposure to corresponding antibiotics; (ii) oral exposure to high doses of Tet and Amp in mice inoculated with AR gene carriers led to rapid enrichment of corresponding AR gene pools in feces; (iii) significantly less or delayed development of AR in the GI tract of the AR carrier-inoculated mice was observed when the same doses of antibiotics were administered via i.v. injection rather than oral administration; and (iv) antibiotic dosage, and maybe the excretion route, affected AR in the GI tract. The shift of dominant AR bacterial populations in the gut microbiota was consistent with the dynamics of AR gene pools. The emergence of endogenous resistant bacteria in the gut microbiota corresponding to drug exposure was also observed. Together, these data suggest that oral administration of antibiotics has a prominent effect on AR amplification and development in gut microbiota, which may be minimized by alternative drug administration approaches, as illustrated by i.v. injection in this study and proper drug selection.

  13. Iptakalim attenuates self-administration and acquired goal-tracking behavior controlled by nicotine.

    PubMed

    Charntikov, S; Swalve, N; Pittenger, S; Fink, K; Schepers, S; Hadlock, G C; Fleckenstein, A E; Hu, G; Li, M; Bevins, R A

    2013-12-01

    Iptakalim is an ATP-sensitive potassium channel opener, as well as an α4β2-containing nicotinic acetylcholine receptor (nAChR) antagonist. Pretreatment with iptakalim diminishes nicotine-induced dopamine (DA) and glutamate release in the nucleus accumbens. This neuropharmacological profile suggests that iptakalim may be useful for treatment of nicotine dependence. Thus, we examined the effects of iptakalim in two preclinical models. First, the impact of iptakalim on the interoceptive stimulus effect of nicotine was evaluated by training rats in a discriminated goal-tracking task that included intermixed nicotine (0.4 mg/kg, SC) and saline sessions. Sucrose was intermittently presented in a response-independent manner only on nicotine sessions. On intervening test days, rats were pretreated with iptakalim (10, 30, 60 mg/kg, IP). Results revealed that iptakalim attenuated nicotine-evoked responding controlled by the nicotine stimulus in a dose-dependent manner. In a separate study, the impact of iptakalim on the reinforcing effects of nicotine was investigated by training rats to lever-press to self-administer nicotine (0.01 mg/kg/infusion) [Dosage error corrected]. Results revealed that pretreatment with iptakalim (1, 3, 6 mg/kg, IV) decreased nicotine intake (i.e., less active lever responding). Neither behavioral effect was due to a non-specific motor effect of iptakalim, nor to an ability of iptakalim to inhibit DA transporter (DAT) or serotonin transporter (SERT) function. Together, these finding support the notion that iptakalim may be an effective pharmacotherapy for increasing smoking cessation and a better understanding of its action could contribute to medication development.

  14. Attenuation of post-infarction remodeling in rats by sustained myocardial growth hormone administration.

    PubMed

    Daskalopoulos, Evangelos P; Vilaeti, Agapi D; Barka, Eleonora; Mantzouratou, Polixeni; Kouroupis, Dimitrios; Kontonika, Marianthi; Tourmousoglou, Christos; Papalois, Apostolos; Pantos, Constantinos; Blankesteijn, W Matthijs; Agathopoulos, Simeon; Kolettis, Theofilos M

    2015-01-01

    Prevention of left ventricular remodeling is an important therapeutic target post-myocardial infarction. Experimentally, treatment with growth hormone (GH) is beneficial, but sustained local administration has not been thoroughly investigated. We studied 58 rats (322 ± 4 g). GH was administered via a biomaterial-scaffold, following in vitro and in vivo evaluation of degradation and drug-release curves. Treatment consisted of intra-myocardial injection of saline or alginate-hydrogel, with or without GH, 10 min after permanent coronary artery ligation. Echocardiographic and histologic remodeling-indices were examined 3 weeks post-ligation, followed by immunohistochemical evaluation of angiogenesis, collagen, macrophages and myofibroblasts. GH-release completed at 3 days and alginate-degradation at ∼7 days. Alginate + GH consistently improved left ventricular end-diastolic and end-systolic diameters, ventricular sphericity, wall tension index and infarct-thickness. Microvascular-density and myofibroblast-count in the infarct and peri-infarct areas were higher after alginate + GH. Macrophage-count and collagen-content did not differ between groups. Early, sustained GH-administration enhances angiogenesis and myofibroblast-activation and ameliorates post-infarction remodeling.

  15. Intranigral administration of substance P receptor antagonist attenuated levodopa-induced dyskinesia in a rat model of Parkinson's disease.

    PubMed

    Yang, Xinxin; Zhao, Hui; Shi, Hongjuan; Wang, Xiaoying; Zhang, Shenyang; Zhang, Zunsheng; Zu, Jie; Zhang, Wei; Shen, Xia; Cui, Guiyun; Hua, Fang

    2015-09-01

    Levodopa (L-dopa) remains the most effective drug in the treatment of Parkinson's disease (PD). However, L-dopa-induced dyskinesia (LID) has hindered its use for PD patients. The mechanisms of LID are not fully understood. Substance P (SP) receptor antagonist has been shown to reduce parkinsonism in animal models of PD, and ameliorate LID in PD rats. But the concrete mechanism is not fully understood. To address this issue, we produced a rat model of PD using 6-hydroxydompamine (6-OHDA) injections, and valid PD rats were intranigrally administrated with different doses of SP receptor antagonist LY303870 (5 nmol/day, 10 nmol/day and 20 nmol/day) following L-dopa (6 mg/kg/day, i.p.) plus benserazide (12 mg/kg/day, i.p.) for 23 days. We found that nigral SP levels were increased on days 3, 7 and 14 and decreased on day 21 after 6-hydroxydompamine lesions. But nigral SP levels kept increasing after repeated L-dopa administration in PD rats. Intranigral administration of low and moderate LY303870 reduced abnormal involuntary movements (AIMs) while improving motor deficits in PD rats treated with L-dopa plus benserazide. Microdialysis revealed that LY303870 (10 nmol/day) treatment attenuated the increase of striatal dopamine and the reduction of γ-aminobutyric acid in ventromedial thalamus of PD rats primed with L-dopa. Additionally, LY303870 (10 nmol/day) treatment prior to L-dopa administration reduced the phosphorylated levels of dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein of 32 kDa at Thr 34 and extracellular signal-regulated kinases 1/2 as well as the levels of activity-regulated cytoskeleton-associated protein and Penk in L-dopa-primed PD rats. Taken together, these data showed that low and moderate SP receptor antagonists LY303870 could ameliorate LID via neurokinin 1 receptor without affecting therapeutic effect of L-dopa.

  16. Time-dependent changes in nicotine behavioral responsivity during early withdrawal from chronic cocaine administration and attenuation of cocaine sensitization by mecamylamine.

    PubMed

    Szabo, Steven T; Fowler, J C; Froeliger, Brett; Lee, Tong H

    2014-04-01

    Cocaine abuse is associated with a high prevalence of nicotine dependence. In animals, nicotinic antagonists have been reported to block the development of cocaine behavioral sensitization and to attenuate cocaine place preference or self-administration. In the present study, we have determined: (1) changes in the locomotor responses to nicotine challenge during the first week of withdrawal from daily cocaine pretreatment; and (2) effects of the non-selective nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine given during the first 5 days of cocaine withdrawal on the maintenance of cocaine behavioral sensitization. Male Sprague-Dawley rats were pretreated with daily saline (SI) or cocaine (CI) injections for 14 days. In Experiment 1, separate animals in the SI and CI groups received a single nicotine challenge on day 1, 3, or 7 of withdrawal from their respective pretreatments. The CI group displayed enhanced locomotor responses to nicotine as compared to SI controls on days 3 and 7 of withdrawal, but not day 1. In Experiment 2, SI and CI animals were treated once a day with either saline or mecamylamine during the first 5 days of withdrawal, and were subsequently challenged with single cocaine injections on both withdrawal days 7 and 14. Mecamylamine treatment significantly attenuated expression of cocaine behavioral sensitization on both withdrawal days 7 and 14. Time-dependent changes in nicotinic responses occur during the first week of cocaine withdrawal, and intact nAChR neurotransmission during this period may be necessary for maintenance of cocaine behavioral sensitization.

  17. Weekly administration of paclitaxel attenuated rectal stenosis caused by multiple peritoneal recurrence 8 years after the resection of gastric carcinoma.

    PubMed

    Sakurai, Yoichi; Yoshida, Ikuo; Tonomura, Shuhei; Sakai, Wakana; Nakamura, Yasuko; Imazu, Hiroki; Matsubara, Toshiki; Ochiai, Masahiro

    2003-01-01

    We report a patient with rectal stenosis caused by peritoneal recurrence 8 years after a curative resection of advanced stage gastric carcinoma; the recurrence was effectively treated with the weekly administration of paclitaxel. The patient was a 66-year-old Japanese woman who was admitted to our hospital complaining of abdominal pain and frequent bowel movements. She had undergone total gastrectomy, due to advanced-stage gastric carcinoma with extensive lymph node metastasis, 8 years before, and had taken an oral anticancer agent, fluoropyrimidine, for 4 years after the operation. Colonofiberscopy performed on admission revealed circumferential rectal stenosis located 10 cm from the anal verge. Barium enema study demonstrated extensive poor expansion of the upper and lower rectum and irregularity of the descending colon. Abdominal computed tomography (CT) scanning revealed wall thickening in the rectum and descending colon. These findings were compatible with rectal stenosis caused by the peritoneal recurrence of gastric carcinoma. Weekly administration of paclitaxel was started. The abdominal symptoms soon disappeared when the second cycle of paclitaxel was completed, and they have not appeared since then. The rectal stenosis was attenuated, as confirmed by imaging analyses. Weekly paclitaxel has been effective for more than 13 months, suggesting that the patient is in a state of tumor dormancy of recurrent gastric carcinoma.

  18. Delayed administration of the nucleic acid analog 2Cl-C.OXT-A attenuates brain damage and enhances functional recovery after ischemic stroke.

    PubMed

    Okabe, Naohiko; Nakamura, Emi; Himi, Naoyuki; Narita, Kazuhiko; Tsukamoto, Ikuko; Maruyama, Tokumi; Sakakibara, Norikazu; Nakamura, Takehiro; Itano, Toshifumi; Miyamoto, Osamu

    2013-04-19

    2Cl-C.OXT-A (COA-Cl) is a novel nucleic acid analog that enhances angiogenesis through extracellular signal-regulated kinase 1 or 2 (ERK1/2) activation. ERK1/2 is a well-known kinase that regulates cell survival, proliferation and differentiation in the central nervous system. We performed in vitro and in vivo experiments to investigate whether COA-Cl can attenuate neuronal damage and enhance recovery after brain ischemia. In primary cortical neuron cultures, COA-Cl prevented neuronal injury after 2h of oxygen-glucose deprivation. COA-Cl increased phospho-ERK levels in a dose-dependent manner and COA-Cl-induced neuroprotection and ERK1/2 activation was inhibited by suramin or PD98059. The effect of COA-Cl was evaluated in vivo with 60min of middle cerebral artery occlusion combined with bilateral common carotid artery occlusion. COA-Cl or saline was injected intracerebroventricularly 5min after reperfusion. COA-Cl significantly reduced infarct volume and improved neurological deficits upon injection of 15 or 30μg/kg COA-Cl. Moreover, COA-Cl reduced the number of TUNEL positive cells in ischemic boundary, while rCBF was not significantly changed by COA-Cl administration. We also evaluated the effect of delayed COA-Cl administration on recovery from brain ischemia by continuous administration of COA-Cl from 1 to 8 days after reperfusion. Delayed continuous COA-Cl administration also reduced infarct volume. Furthermore, COA-Cl enhanced peri-infarct angiogenesis and synaptogenesis, resulting in improved motor function recovery. Our findings demonstrate that COA-Cl exerts both neuroprotective and neurorestorative effects over a broad therapeutic time window, suggesting COA-Cl might be a novel and potent therapeutic agent for ischemic stroke.

  19. Annual committee reports on significant legislative, judicial and administrative developments in 1983: Air-Quality Committee

    SciTech Connect

    Not Available

    1984-01-01

    Congress passed no significant amendments to the Clean Air Act (CAA) in 1983. Under judicial developments, the committee describes seven categories of cases concerning: nonattainment areas under CAA section 107, the adequacy and appropriateness of state implementation plans and regulation of interstate air pollution, new source-permitting cases, regulation of hazardous air pollutants, enforcement and attorneys fees and the scope of section 304 and 307 of the CAA, sections 120 and 123 of the CAA, and 1983 Title II cases. Administration developments included new steps under Titles I and II of the CAA taken by the Environmental Protection Agency to promulgate final regulation on nonattainment sanctions and new source standards and to revise hydrocarbon and carbon monoxide standards for heavy-duty engines and for vehicles at high altitudes. 264 references.

  20. The dopamine receptor antagonist levo-tetrahydropalmatine attenuates heroin self-administration and heroin-induced reinstatement in rats.

    PubMed

    Yue, Kai; Ma, Baomiao; Ru, Qin; Chen, Lin; Gan, Yongping; Wang, Daisong; Jin, Guozhang; Li, Chaoying

    2012-07-01

    Opiate addiction is a chronic recrudescent disorder characterized by a high rate of relapse. Levo-tetrahydropalmatine (l-THP) is an alkaloid substance extracted from Corydalis and Stephania and is contained in a number of traditional Chinese herbal preparations. Compared to other dopamine receptor antagonists, l-THP has lower affinity for D2 receptors than for D1 receptors, and a recent study showed that l-THP also binds to D3 receptors, possibly functioning as an antagonist. The unique pharmacological profile of l-THP suggests that l-THP may be effective for the treatment of opiate addiction. In this study, we investigated the effects of l-THP on heroin self-administration and reinstatement triggered by a priming injection of heroin in abstinent rats trained to stably self-administer heroin under an extinction/reinstatement protocol, and found that l-THP (2.5 and 5 mg/kg, i.p.) decreased heroin self-administration on the fixed-ratio 1 schedule and dose-dependently (1.25, 2.5 and 5 mg/kg, i.p.) inhibited heroin-induced reinstatement of heroin-seeking behavior. Importantly, l-THP (1.25 and 2.5 mg/kg, i.p.) did not affect locomotion, indicating that the observed effects of l-THP on reinstatement do not appear to be due to motor impairments. The present results demonstrated that dopamine receptor antagonist l-THP attenuates heroin self-administration and heroin-induced reinstatement.

  1. Repeated intravenous administrations of teneurin-C terminal associated peptide (TCAP)-1 attenuates reinstatement of cocaine seeking by corticotropin-releasing factor (CRF) in rats.

    PubMed

    Erb, Suzanne; McPhee, Matthew; Brown, Zenya J; Kupferschmidt, David A; Song, Lifang; Lovejoy, David A

    2014-08-01

    The teneurin c-terminal associated peptides (TCAP) have been implicated in the regulation of the stress response, possibly via a corticotropin-releasing factor (CRF)-related mechanism. We have previously shown that repeated intracerebroventricular (ICV) injections of TCAP-1 attenuate the reinstatement of cocaine seeking by CRF in rats. Here, we determined whether intravenous (IV) administrations of TCAP-1 would likewise attenuate CRF-induced reinstatement, and whether this effect would vary depending on the rat's history of cocaine self administration. Rats were trained to self-administer cocaine for 10 days, during once daily sessions that were either 3h ("short access"; ShA) or 6h ("long access"; LgA). Rats were then given five daily injections of TCAP-1 (0, 300, or 3,000 pmol, IV) in their home cage. Subsequently, they were returned to the self-administration chambers where extinction of cocaine seeking and testing for CRF-induced reinstatement of cocaine seeking was carried out. Repeated IV administrations of TCAP-1 were efficacious in attenuating CRF-induced reinstatement of cocaine seeking, but at different doses in ShA and LgA rats. Taken together, the findings extend previous work showing a consistent effect of repeated ICV TCAP-1 on CRF-induced reinstatement of cocaine seeking, and point to a potential therapeutic benefit of TCAP-1 in attenuating cocaine seeking behaviors.

  2. Systemic administration of attenuated Salmonella choleraesuis carrying thrombospondin-1 gene leads to tumor-specific transgene expression, delayed tumor growth and prolonged survival in the murine melanoma model.

    PubMed

    Lee, Che-Hsin; Wu, Chao-Liang; Shiau, Ai-Li

    2005-02-01

    Some anaerobic and facultative anaerobic bacteria have been used experimentally as anticancer agents because of their selective growth in the hypoxia regions of solid tumors after systemic administration. We have previously shown the feasibility of using attenuated Salmonella choleraesuis as a gene delivery vector. In this study, we exploited S. choleraesuis carrying thrombospondin-1 (TSP-1) gene for treating primary melanoma and experimental pulmonary metastasis in the syngeneic murine B16F10 melanoma model. Systemic administration of S. choleraesuis allowed targeted gene delivery to tumors. The bacteria accumulated preferentially in tumors over livers and spleens at ratios ranging from 1000:1 to 10,000:1. The level of transgene expression via S. choleraesuis-mediated gene transfer in tumors could reach more than 1800-fold higher than in livers and spleens. Notably, bacterial accumulation was also observed in the lungs with metastatic nodules, but not in healthy lungs. When administered into mice bearing subcutaneous or pulmonary metastatic melanomas, S. choleraesuis carrying TSP-1 gene significantly inhibited tumor growth and enhanced survival of the mice. Immunohistochemical studies in the tumors from these mice displayed decreased intratumoral microvessel density. Taken together, these findings suggest that TSP-1 gene therapy delivered by S. choleraesuis may be effective for the treatment of primary as well as metastatic melanomas.

  3. Chronic L-DOPA treatment attenuates behavioral and biochemical deficits induced by unilateral lactacystin administration into the rat substantia nigra.

    PubMed

    Konieczny, Jolanta; Czarnecka, Anna; Lenda, Tomasz; Kamińska, Kinga; Lorenc-Koci, Elżbieta

    2014-03-15

    The aim of the study was to determine whether the dopamine (DA) precursor l-DOPA attenuates parkinsonian-like symptoms produced by the ubiquitin-proteasome system inhibitor lactacystin. Wistar rats were injected unilaterally with lactacystin (2.5 μg/2 μl) or 6-OHDA (8 μg/2 μl) into the substantia nigra (SN) pars compacta. Four weeks after the lesion, the animals were treated chronically with l-DOPA (25 or 50 mg/kg) for two weeks. During l-DOPA treatment, the lactacystin-treated rats were tested for catalepsy and forelimb asymmetry. Rotational behavior was evaluated after apomorphine (0.25 mg/kg) and l-DOPA in both PD models. After completion of experiments, the animals were killed and the levels of DA and its metabolites in the striatum and SN were assayed. We found that acute l-DOPA administration effectively decreased catalepsy and increased the use of the compromised forelimb in the cylinder test. However, the lactacystin group did not respond to apomorphine or acute l-DOPA administration in the rotational test. Repeated l-DOPA treatment produced contralateral rotations in both PD models, but the number of rotations was much greater in the 6-OHDA-lesioned rats. Both toxins markedly (>90%) reduced the levels of DA and its metabolites in the striatum and SN, while l-DOPA diminished these decreases, especially in the SN. By demonstrating the efficacy of l-DOPA in several behavioral tests, our study confirms the usefulness of the lactacystin lesion as a model of PD. However, marked differences in the rotational response to apomorphine and l-DOPA suggest different mechanisms of neurodegeneration evoked by lactacystin and 6-OHDA.

  4. Spinal administration of a delta opioid receptor agonist attenuates hyperalgesia and allodynia in a rat model of neuropathic pain.

    PubMed

    Holdridge, Sarah V; Cahill, Catherine M

    2007-08-01

    Neuropathic (NP) pain is a debilitating chronic pain disorder considered by some to be inherently resistant to therapy with traditional analgesics. Indeed, micro opioid receptor (OR) agonists show reduced therapeutic benefit and their long term use is hindered by the high incidence of adverse effects. However, pharmacological and physiological evidence increasingly suggests a role for deltaOR agonists in modulating NP pain symptoms. In this study, we examined the antihyperalgesic and antiallodynic effects of the spinally administered deltaOR agonist, d-[Ala(2), Glu(4)]deltorphin II (deltorphin II), as well as the changes in deltaOR expression, in rats following chronic constriction injury (CCI) of the sciatic nerve. Rats with CCI exhibited cold hyperalgesia and mechanical allodynia over a 14-day testing period. Intrathecal administration of deltorphin II reversed cold hyperalgesia on day 14 and dose-dependently attenuated mechanical allodynia. The effects of deltorphin II were mediated via activation of the deltaOR as the effect was antagonized by co-treatment with the delta-selective antagonist, naltrindole. Western blotting experiments revealed no changes in deltaOR protein in the dorsal spinal cord following CCI. Taken together, these data demonstrate the antihyperalgesic and antiallodynic effectiveness of a spinally administered deltaOR agonist following peripheral nerve injury and support further investigation of deltaORs as potential therapeutic targets in the treatment of NP pain.

  5. Long-term administration of pyridostigmine attenuates pressure overload-induced cardiac hypertrophy by inhibiting calcineurin signalling.

    PubMed

    Lu, Yi; Zhao, Ming; Liu, Jin-Jun; He, Xi; Yu, Xiao-Jiang; Liu, Long-Zhu; Sun, Lei; Chen, Li-Na; Zang, Wei-Jin

    2017-03-10

    Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload-induced cardiac hypertrophy and identify the underlying mechanisms. Rats were subjected to either sham or constriction of abdominal aorta surgery and treated with or without pyridostigmine for 8 weeks. Vagal activity and cardiac function were determined using PowerLab. Cardiac hypertrophy was evaluated using various histological stains. Protein markers for cardiac hypertrophy were quantitated by Western blot and immunoprecipitation. Pressure overload resulted in a marked reduction in vagal discharge and a profound increase in cardiac hypertrophy index and cardiac dysfunction. Pyridostigmine increased the acetylcholine levels by inhibiting acetylcholinesterase in rats with pressure overload. Pyridostigmine significantly attenuated cardiac hypertrophy based on reduction in left ventricular weight/body weight, suppression of the levels of atrial natriuretic peptide, brain natriuretic peptide and β-myosin heavy chain, and a reduction in cardiac fibrosis. These effects were accompanied by marked improvement of cardiac function. Additionally, pyridostigmine inhibited the CaN/NFAT3/GATA4 pathway and suppressed Orai1/STIM1 complex formation. In conclusion, pressure overload resulted in cardiac hypertrophy, cardiac dysfunction and a significant reduction in vagal discharge. Pyridostigmine attenuated cardiac hypertrophy and improved cardiac function, which was related to improved cholinergic transmission efficiency (decreased acetylcholinesterase and increased acetylcholine), inhibition of the CaN/NFAT3/GATA4

  6. Developmental lead exposure attenuates methamphetamine dose-effect self-administration performance and progressive ratio responding in the male rat.

    PubMed

    Rocha, Angelica; Valles, Rodrigo; Hart, Nigel; Bratton, Gerald R; Nation, Jack R

    2008-06-01

    Perinatal (gestation/lactation) lead exposure modifies the reinforcement efficacy of various psychoactive drugs (e.g., cocaine, opiates) across the phases of initial selection, use, and abuse [Nation J.R., Cardon A.L., Heard H.M., Valles R., Bratton G.R. Perinatal lead exposure and relapse to drug-seeking behavior in the rat: a cocaine reinstatement study. Psychopharmacol 2003;168: 236-243.; Nation J.R., Smith K.R., Bratton G.R. Early developmental lead exposure increases sensitivity to cocaine in a self-administration paradigm. Pharmacol Biochem Behave 2004; 77: 127-13; Rocha A., Valles R., Cardon A.L., Bratton G.R., Nation J.R. Enhanced acquisition of cocaine self-administration in rats developmentally exposed to lead. Neuropsychopharmacol 2005; 30: 2058-2064.]. However, changes in sensitivity to methamphetamine across the phases of drug abuse have not been examined in animals perinatally exposed to lead. Because the mainstream popularity of methamphetamine in the United States is increasing and lead exposure continues to be widespread, an examination of this drug and how it may be modified by perinatal exposure to lead is warranted. The studies reported here examined the effects of perinatal lead exposure on adult self-administration of intravenous (i.v.) methamphetamine across the maintenance phase of drug addiction. Experiment 1 examined dose-effect patterns in control and lead-exposed animals. Experiment 2 evaluated control and lead-exposed animals in a progressive ratio task. Female rats were administered a 16-mg lead or a control solution for 30 days prior to breeding with non-exposed males. Exposure continued through pregnancy and lactation and was discontinued at weaning (postnatal day [PND] 21). Animals born to control or lead-exposed dams received indwelling jugular catheters as adults (PND 70) and subsequently were randomly assigned to one of the two studies, using only one male rat per litter for each study. The data showed a general attenuation of

  7. Alcohol administration attenuates hypothalamic-pituitary-adrenal (HPA) activity in healthy men at low genetic risk for alcoholism, but not in high-risk subjects.

    PubMed

    Mick, Inge; Spring, Konstanze; Uhr, Manfred; Zimmermann, Ulrich S

    2013-09-01

    Acute alcohol challenge studies in rodents and naturalistic observations in drinking alcoholics suggest that alcohol stimulates the hypothalamic-pituitary-adrenal (HPA) system. The literature on respective studies in healthy volunteers is more inconsistent, suggesting differential alcohol effects depending on dosage, recent drinking history, family history of alcoholism and alcohol-induced side effects. These papers and the putative pharmacologic mechanisms underlying alcohol effects on the HPA system are reviewed here and compared with a new study, in which we investigated how secretion of adrenocorticotrophin (ACTH) and cortisol is affected by ingestion of 0.6 g/kg ethanol in 33 young healthy socially drinking males with a paternal history of alcoholism (PHP) versus 30 family history negative (FHN) males. Alcohol and placebo were administered in a 2-day, double-blind, placebo controlled crossover design with randomized administration sequence. After administration of placebo, ACTH and cortisol decreased steadily over 130 minutes. In FHN subjects, secretion of both hormones was even more attenuated after alcohol, resulting in significantly lower levels compared with placebo. In PHP subjects, no alcohol effect on hormone secretion could be detected. The ratio of cortisol to ACTH secretion, each expressed as area under the secretion curve, was significantly increased by alcohol in FHN and PHP participants. These results argue against HPA stimulation being a mechanism that promotes the transition from moderate to dependent drinking. The fact that alcohol-induced HPA suppression was not detected in PHP males is consistent with the general concept that subjects at high risk for alcoholism exhibit less-pronounced alcohol effects.

  8. 21 CFR 10.70 - Documentation of significant decisions in administrative file.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... decision on any matter under the laws administered by the Commissioner, whether it is raised formally, for... handling a matter are responsible for insuring the completeness of the administrative file relating to it... supervisory personnel, responsible for handling the matter. (i) The recommendations and decisions are...

  9. 21 CFR 10.70 - Documentation of significant decisions in administrative file.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... decision on any matter under the laws administered by the Commissioner, whether it is raised formally, for... handling a matter are responsible for insuring the completeness of the administrative file relating to it... supervisory personnel, responsible for handling the matter. (i) The recommendations and decisions are...

  10. Delayed Administration of Pyroglutamate Helix B Surface Peptide (pHBSP), a Novel Nonerythropoietic Analog of Erythropoietin, Attenuates Acute Kidney Injury

    PubMed Central

    Patel, Nimesh S A; Kerr-Peterson, Hannah L; Brines, Michael; Collino, Massimo; Rogazzo, Mara; Fantozzi, Roberto; Wood, Elizabeth G; Johnson, Florence L; Yaqoob, Muhammad M; Cerami, Anthony; Thiemermann, Christoph

    2012-01-01

    In preclinical studies, erythropoietin (EPO) reduces ischemia-reperfusion–associated tissue injury (for example, stroke, myocardial infarction, acute kidney injury, hemorrhagic shock and liver ischemia). It has been proposed that the erythropoietic effects of EPO are mediated by the classic EPO receptor homodimer, whereas the tissue-protective effects are mediated by a hetero-complex between the EPO receptor monomer and the β-common receptor (termed “tissue-protective receptor”). Here, we investigate the effects of a novel, selective-ligand of the tissue-protective receptor (pyroglutamate helix B surface peptide [pHBSP]) in a rodent model of acute kidney injury/dysfunction. Administration of pHBSP (10 μg/kg intraperitoneally [i.p.] 6 h into reperfusion) or EPO (1,000 IU/kg i.p. 4 h into reperfusion) to rats subjected to 30 min ischemia and 48 h reperfusion resulted in significant attenuation of renal and tubular dysfunction. Both pHBSP and EPO enhanced the phosphorylation of Akt (activation) and glycogen synthase kinase 3β (inhibition) in the rat kidney after ischemia-reperfusion, resulting in prevention of the activation of nuclear factor-κB (reduction in nuclear translocation of p65). Interestingly, the phosphorylation of endothelial nitric oxide synthase was enhanced by EPO and, to a much lesser extent, by pHBSP, suggesting that the signaling pathways activated by EPO and pHBSP may not be identical. PMID:22415011

  11. Rhenium-coated glass beads for intracolonic administration attenuate TNBS-induced colitis in mice: Proof-of-Concept Study.

    PubMed

    Siczek, Krzysztof; Zatorski, Hubert; Pawlak, Wojciech; Fichna, Jakub

    2015-01-01

    In search for novel effective treatments in inflammatory bowel diseases, a new strategy employing glass beads coated with rhenium nanolayer has been developed and validated in the mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Briefly, mice were randomly divided into 5 experimental groups: control (vehicle alone, Group 1); control treated with rhenium-coated glass beads (Group 2); TNBS (Group 3); TNBS treated with rhenium-coated glass beads (Group 4); and TNBS treated with uncoated glass beads (Group 5). Mice from Group 2, 4 and 5 were treated with respective beads (once daily, 5 beads / animal, i.c.) between D3-D6 post-TNBS/vehicle and evaluation of colonic damage was performed on D7, based on macroscopic scoring and clinical parameters. Severe colonic inflammation developed in post-TNBS mice (Group 3) [P <0.001 vs. control (Group 1) for macroscopic score], which was significantly attenuated by treatment with rhenium-coated glass beads (Group 4) [P <0.01 vs. TNBS (Group 3), for macroscopic score]. Neither rhenium-coated glass beads had any effect in control animals (Group 2), nor uncoated glass beads influenced TNBS-induced colitis (Group 5). In conclusion, a novel and attractive strategy for the treatment of colonic inflammation has been proposed; therapy with rhenium-coated glass beads already proved effective in the mouse model of TNBS-induced colitis, now requires further characterization in clinical conditions.

  12. Intrathecal administration of rapamycin inhibits the phosphorylation of DRG Nav1.8 and attenuates STZ-induced painful diabetic neuropathy in rats.

    PubMed

    He, Wan-You; Zhang, Bin; Xiong, Qing-Ming; Yang, Cheng-Xiang; Zhao, Wei-Cheng; He, Jian; Zhou, Jun; Wang, Han-Bing

    2016-04-21

    The mammalian target of rapamycin (mTOR) is a key regulator of mRNA translation and protein synthesis, and it is specifically inhibited by rapamycin. In chronic pain conditions, mTOR-mediated local protein synthesis is crucial for neuronal hyperexcitability and synaptic plasticity. The tetrodotoxin-resistant (TTX-R) sodium channel Nav1.8 plays a major role in action potential initiation and propagation and cellular excitability in DRG (dorsal root ganglion) neurons. In this study, we investigated if mTOR modulates the phosphorylation of Nav1.8 that is associated with neuronal hyperexcitability and behavioral hypersensitivity in STZ-induced diabetic rats. Painful diabetic neuropathy (PDN) was induced in Sprague-Dawley rats by intraperitoneal injection with streptozotocin (STZ) at 60mg/kg. After the onset of PDN, the rats received daily intrathecal administrations of rapamycin (1μg, 3μg, or 10μg/day) for 7 days; other diabetic rats received the same volumes of dimethyl sulfoxide (DMSO). Herein, we demonstrate a marked increase in protein expression of total mTOR and phospho-mTOR (p-mTOR) together with the up-regulation of phosphor-Nav1.8 (p-Nav1.8) prior to the mechanical withdrawal threshold reaching a significant reduction in dorsal root ganglions (DRGs). Furthermore, the intrathecal administration of rapamycin, inhibiting the activity of mTOR, suppressed the phosphorylation of DRG Nav1.8, reduced the TTX-R current density, heightened the voltage threshold for activation and lowered the voltage threshold for inactivation and relieved mechanical hypersensitivity in diabetic rats. An intrathecal injection (i.t.) of rapamycin inhibited the phosphorylation and enhanced the functional availability of DRG Nav1.8 attenuated STZ-induced hyperalgesia. These results suggest that rapamycin is a potential therapeutic intervention for clinical PDN.

  13. Choline supplementation attenuates learning deficits associated with neonatal alcohol exposure in the rat: effects of varying the timing of choline administration.

    PubMed

    Ryan, S Hunter; Williams, Jennifer K; Thomas, Jennifer D

    2008-10-27

    Despite the harmful effects of fetal alcohol exposure, some pregnant women continue to drink alcohol. Thus, it is imperative to pursue safe, effective treatments for children with fetal alcohol spectrum disorders. Using an animal model, our laboratory has demonstrated that choline, an essential nutrient, effectively reduces the severity of some fetal alcohol effects, even when administered after the ethanol insult is complete. The present study investigated whether there is a critical developmental period when choline is most effective in attenuating ethanol's teratogenic effects. Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol during the third trimester equivalent brain growth spurt (postnatal days (PD) 4-9) via intubation. A non-intubation control group and a sham intubation control group were included. Following ethanol exposure, pups received subcutaneous injections of saline vehicle or choline chloride (100 mg/kg/day) from PD 11-20, PD 21-30, or PD 11-30. Beginning on PD 45, subjects were tested on a Morris water maze spatial learning task. Performance of both the ethanol-exposed group that did not receive choline and the ethanol-exposed group treated with choline from PD 21-30 was significantly impaired compared to controls during acquisition of the Morris water maze task. Performance of ethanol-exposed groups treated with choline from PD 11-20 or PD 11-30 was intermediate, not differing significantly from any other groups. However, during the probe trial, ethanol exposure produced significant deficits in spatial memory which were mitigated by all choline treatments, regardless of the timing of administration. These findings suggest that choline's therapeutic window may be very large, or spans across the two developmental periods examined in this study. Importantly, these findings indicate that choline supplementation may effectively reduce some alcohol-related learning impairments, even when administered in later childhood.

  14. Chronic administration of oxprenolol and metoprolol attenuate sympathetic cardiovascular responses only in non-adrenalectomized pithed rats.

    PubMed

    Vila, E; Badia, A

    1995-10-01

    1. Oxprenolol and metoprolol (30 mg kg-1) were injected intraperitoneally (i.p.) for 1 day (acute treatment) and 6 weeks (chronic treatment) to Sprague-Dawley rats. 2. Increases of mean blood pressure and heart rate to noradrenaline (0.1-10 micrograms kg-1) and to electrical stimulation (0.5 msec, supramax V, 0.25-5 Hz) of the entire sympathetic outflow were measured in non-adrenalectomized (acute and chronic) and adrenalectomized (chronic) pithed rats. 3. Acute beta-adrenoceptor antagonist administration was without effect on mean blood pressure and heart rate increases to noradrenaline and electrical stimulation. 4. Chronic administration with oxprenolol significantly diminished the stimulation-induced increases of mean blood pressure and heart rate in non-adrenalectomized pithed rats. 5. Increases in heart rate, elicited by stimulation of the entire sympathetic outflow in non-adrenalectomized but not in adrenalectomized pithed rats, were decreased by metoprolol treatment. Both treatments were without effect on noradrenaline responses. 6. These results indicate that chronic beta-adrenoceptor antagonist treatment is associated with a reduction in the cardiovascular responses to sympathetic nerve-stimulation. However, this mechanism only operates when adrenomedullary adrenaline is present to facilitate the noradrenaline release through activation of presynaptic beta 2-adrenoceptors.

  15. Significant mucosal sIgA production after a single oral or parenteral administration using in vivo CD40 targeting in the chicken.

    PubMed

    Chou, Wen-Ko; Chen, Chang-Hsin; Vuong, Christine N; Abi-Ghanem, Daad; Waghela, Suryakant D; Mwangi, Waithaka; Bielke, Lisa R; Hargis, Billy M; Berghman, Luc R

    2016-10-01

    Many pathogens enter the host through mucosal surfaces and spread rapidly via the circulation. The most effective way to prevent disease is to establish mucosal and systemic immunity against the pathogen. However, current vaccination programs in poultry industry require repeated administrations of live-attenuated virus or large amounts (10 to 100μg) of antigen together with adjuvant to induce specific secretory IgA immune responses at the mucosal effector sites. In the present study, we show that a single administration of 0.4μg of oligopeptide complexed with an agonistic anti-chicken CD40 (chCD40) monoclonal antibody (Mab) effectively targets antigen-presenting cells of the bird's mucosa-associated lymphoid tissue in vivo, and induces peptide-specific secretory IgA (sIgA) in the trachea 7days post administration. Anti-chCD40 Mab-peptide complex was administered once to four-week old male Leghorns via various mucosal routes (orally, via cloacal drinking, or oculo-nasally) or via subcutaneous (s.c.) immunization. Immunization through any of the three mucosal induction routes induced significant peptide-specific mucosal sIgA responses 7 and 14days after immunization. Interestingly, s.c. injection of the complex also induced mucosal sIgA. Our data suggest in vivo targeting of CD40 as a potential adjuvant platform, particularly for the purpose of enhancing and speeding up mucosal vaccine responses in chickens, and potentially other food animals. This is the first study able to elicit specific sIgA immune responses in remote mucosal sites with a single administration of only 0.4μg of antigen.

  16. Exogenous administration of thiosulfate, a donor of hydrogen sulfide, attenuates angiotensin II-induced hypertensive heart disease in rats

    PubMed Central

    Snijder, P M; Frenay, A R; de Boer, R A; Pasch, A; Hillebrands, J L; Leuvenink, H G D; van Goor, H

    2015-01-01

    Background and Purpose Hypertension is an important mediator of cardiac damage and remodelling. Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter with cardioprotective properties. However, it is not yet in clinical use. We, therefore, investigated the protective effects of sodium thiosulfate (STS), a clinically applicable H2S donor substance, in angiotensin II (Ang II)-induced hypertensive cardiac disease in rats. Experimental Approach Male Sprague Dawley rats were infused with Ang II (435 ng kg min−1) or saline (control) for 3 weeks via s.c. placed osmotic minipumps. During these 3 weeks, rats received i.p. injections of either STS, NaHS or vehicle (0.9% NaCl). Key Results Compared with controls, Ang II infusion caused an increase in systolic and diastolic BP with associated cardiac damage as evidenced by cardiac hypertrophy, an increase in atrial natriuretic peptide (ANP) mRNA, cardiac fibrosis and increased oxidative stress. Treatment with NaHS and STS prevented the development of hypertension and the increase in ANP mRNA levels. Furthermore, the degree of cardiac hypertrophy, the extent of histological fibrosis in combination with the expression of profibrotic genes and the levels of oxidative stress were all significantly decreased. Conclusions and Implications Ang II-induced hypertensive cardiac disease can be attenuated by treatment with STS and NaHS. Although BP regulation is the most plausible mechanism of cardiac protection, the antifibrotic and antioxidant properties of released sulfide may also contribute to their effects. Our data show that H2S might be a valuable addition to the already existing antihypertensive and cardioprotective therapies. Linked Articles This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6 PMID:24962324

  17. Long-term administration of inulin-type fructans has no significant lipid-lowering effect in normolipidemic humans.

    PubMed

    Forcheron, Fabien; Beylot, Michel

    2007-08-01

    Short-term studies have shown that the addition to diet of inulin-type fructans, a nondigestible carbohydrate, may have a plasma lipid-lowering effect in humans. Whether this beneficial effect persists during long-term administration has not been determined. The study was aimed at determining whether a prolonged (6 months) administration of inulin-type fructans to healthy subjects has a lipid-lowering action. In a double-blind, randomized, placebo-controlled study, 17 healthy subjects were studied before and after 6 months of daily administration of placebo (8 subjects) or 10 g of a mix of inulin and oligofructose (9 subjects). During this 6-month period, they consumed their usual diet and did not modify their everyday way of life. We measured plasma lipid concentrations; cholesterol synthesis and hepatic lipogenesis; and adipose tissue and circulating mononuclear cell messenger RNA concentrations of key regulatory genes of cholesterol metabolism. Compared with the administration of placebo, the administration of inulin-type fructans had no effect on plasma triacylglycerol concentrations and hepatic lipogenesis and induced only a nonsignificant trend for decreased plasma total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol concentration. Cholesterol synthesis was not significantly modified. Of all the messenger RNA concentrations measured, none was significantly modified by the administration of inulin-type fructans. In conclusion, contrary to what was observed in short-term studies, we observed no significant beneficial effect of a long-term (6-month) administration of inulin-type fructans on plasma lipids in healthy human subjects.

  18. Annual committee reports on significant legislative, judicial, and administrative developments in 1980: Environmental Quality Committee

    SciTech Connect

    Not Available

    1981-01-01

    The reporting responsibilities of the Environmental Quality Committee cover those major federal environmental statutes not covered by the Air Quality, Water Quality, Urban Environment, or Public Lands and Land Use Committees. The 1980 report includes significant developments under the National Environmental Policy Act, the Federal Insecticide, Fungicide and Rodenticide Act, the Toxic Substances Control Act, the Endangered Species Act, the Resource Conservation and Recovery Act, and the Comprehensive Environmental Response, Compensation, and Liability Act (Superfund). The dates of publication and page references in the Federal Register list the final procedures by agency in the appendix. 392 references.

  19. The GABAB Positive Allosteric Modulator, ADX71441 Attenuates Alcohol Self-Administration and Relapse to Alcohol Seeking in Rats.

    PubMed

    Augier, Eric; Dulman, Russell S; Damadzic, Ruslan; Pilling, Andrew; Hamilton, J Paul; Heilig, Markus

    2017-03-15

    GABAergic signaling is involved in modulating the reinforcing properties of alcohol, and GABAB receptors have been proposed as a potential target for clinical treatment of alcoholism. The orthosteric GABAB receptor agonist baclofen has been shown to suppress operant self-administration of alcohol in animals and alcohol use in alcohol dependent patients, but its utility is limited by a narrow therapeutic index. We tested the effects of ADX71441, a novel GABAB receptor positive allosteric modulator on alcohol-related behaviors in rats. We first assessed the effects of ADX71441 (1, 3, 10 and 30 mg/kg, I.P.) on both non-dependent and dependent male Wistar rats trained to self-administer 20% alcohol. We then determined the effects of ADX71441 on stress-induced as well as cue-induced relapse-like behavior. Finally, we sought to identify the brain regions through which ADX71441 may act to prevent relapse-like behavior by mapping the neuronal activation induced by stress-induced reinstatement of alcohol-seeking using c-Fos immunohistochemistry. ADX71441 dose-dependently decreased alcohol self-administration of both dependent and non-dependent animals, but its potency was higher in alcohol-dependent rats. Furthermore, both cue- and stress-induced alcohol seeking were blocked by the GABAB receptor positive allosteric modulator. Finally, pretreatment with 3 mg/kg of ADX71441 before stress-induced reinstatement significantly decreased c-Fos expression in a network of brain regions implicated in stress induced relapse, comprising the nucleus accumbens shell, the dorsal raphe nucleus and the medial prefrontal cortex. Our findings support a causal role of GABAB receptors in alcohol reinforcement and relapse to alcohol seeking. These effects are observed in the absence of significant sedative side effects. Jointly, these observations indicate that GABAB receptor positive allosteric modulators merit being tested clinically for the treatment of alcoholism. Our data also point to

  20. Maternal Intravenous Administration of Azithromycin Results in Significant Fetal Uptake in a Sheep Model of Second Trimester Pregnancy

    PubMed Central

    Miura, Yuichiro; Payne, Matthew S.; Jobe, Alan H.; Kallapur, Suhas G.; Saito, Masatoshi; Stock, Sarah J.; Spiller, O. Brad; Ireland, Demelza J.; Yaegashi, Nobuo; Clarke, Michael; Hahne, Dorothee; Rodger, Jennifer; Keelan, Jeffrey A.; Newnham, John P.

    2014-01-01

    Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks of gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation age-approriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intra-amniotic AZ dose or repeated maternal intravenous (i.v.) AZ doses would safely yield therapeutic levels of AZ in an 80-day-gestation (term is 150 days) ovine fetus. Fifty sheep carrying single pregnancies at 80 days gestation were randomized to receive either: (i) a single intra-amniotic AZ administration or (ii) maternal intravenous AZ administration every 12 h. Amniotic fluid, maternal plasma, and fetal AZ concentrations were determined over a 5-day treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure. A single intra-amniotic administration yielded significant AZ accumulation in the amniotic fluid and fetal lung. In contrast, repeated maternal intravenous administrations achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in the fetal plasma drug concentration at 120 h. There was no evidence of fetal injury in response to drug exposure. These data suggest that (i) repeated maternal i.v. AZ dosing yields substantial fetal tissue uptake, although fetal plasma drug levels remain low; (ii) transfer of AZ from the amniotic fluid is less than transplacental transfer; and (iii) exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein 1 concentrations, or hepatotoxicity, all consistent with an absence of fetal injury. PMID:25155606

  1. Annual committee reports on significant legislative, judicial and administrative developments in 1983: Solid and Hazardous Waste Committee

    SciTech Connect

    Not Available

    1984-01-01

    There were several significant developments under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA or Superfund), the Resource Conservation and Recovery Act (RCRA), and the Toxic Substance Act (TSCA). Court cases on CERCLA involved basic liability issues, prerequisites to actions, and several miscellaneous issues, while adminstrative developments included issuing the national priorities list and amendments to the National Contingency Plan. Court decisions under RCRA addressed liability of those accepting wastes. The Environmental Protection Agency issued a new definition of solid waste and new regulations. Administrative developments under TSCA covered integrated control programs for new and existing chemicals, the collection of information on existing chemicals, and enforcement and inspection activities. 228 references.

  2. Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice.

    PubMed

    Gallo, Linda A; Ward, Micheal S; Fotheringham, Amelia K; Zhuang, Aowen; Borg, Danielle J; Flemming, Nicole B; Harvie, Ben M; Kinneally, Toni L; Yeh, Shang-Ming; McCarthy, Domenica A; Koepsell, Hermann; Vallon, Volker; Pollock, Carol; Panchapakesan, Usha; Forbes, Josephine M

    2016-05-26

    Blood glucose control is the primary strategy to prevent complications in diabetes. At the onset of kidney disease, therapies that inhibit components of the renin angiotensin system (RAS) are also indicated, but these approaches are not wholly effective. Here, we show that once daily administration of the novel glucose lowering agent, empagliflozin, an SGLT2 inhibitor which targets the kidney to block glucose reabsorption, has the potential to improve kidney disease in type 2 diabetes. In male db/db mice, a 10-week treatment with empagliflozin attenuated the diabetes-induced upregulation of profibrotic gene markers, fibronectin and transforming-growth-factor-beta. Other molecular (collagen IV and connective tissue growth factor) and histological (tubulointerstitial total collagen and glomerular collagen IV accumulation) benefits were seen upon dual therapy with metformin. Albuminuria, urinary markers of tubule damage (kidney injury molecule-1, KIM-1 and neutrophil gelatinase-associated lipocalin, NGAL), kidney growth, and glomerulosclerosis, however, were not improved with empagliflozin or metformin, and plasma and intra-renal renin activity was enhanced with empagliflozin. In this model, blood glucose lowering with empagliflozin attenuated some molecular and histological markers of fibrosis but, as per treatment with metformin, did not provide complete renoprotection. Further research to refine the treatment regimen in type 2 diabetes and nephropathy is warranted.

  3. N,N-Dimethylacetamide Significantly Attenuates LPS- and TNFα-Induced Proinflammatory Responses Via Inhibition of the Nuclear Factor Kappa B Pathway

    PubMed Central

    Pekson, Ryan; Poltoratsky, Vladimir; Gorasiya, Samir; Sundaram, Sruthi; Ashby, Charles R; Vancurova, Ivana; Reznik, Sandra E

    2016-01-01

    Previously, we have shown that N,N-dimethylacetamide (DMA) prevents inflammation-induced preterm birth in a murine model, inhibits lipopolysaccharide (LPS)-induced increases in placental proinflammatory cytokines and upregulates the antiinflammatory cytokine interleukin-10 (IL-10). However, DMA’s mechanism of action remains to be elucidated. In the current study, we investigate how DMA produces its antiinflammatory effect. Using in vitro and ex vivo models, we show that DMA suppresses secretion of proinflammatory cytokines in lipopolysaccharide (LPS)-induced RAW 264.7 cells, TNFα-challenged JEG-3 cells and LPS-stimulated human placental explants. DMA significantly attenuated secretion of TNFα, IL-6, IL-10 and granulocyte macrophage colony stimulating factor (GM-CSF) from LPS-stimulated RAW 264.7 cells; IL-6 secretion from TNFα-stimulated JEG-3 cells; and TNFα, IL-6, IL-10, GM-CSF and Interleukin-8 (IL-8) from LPS-stimulated human placental explants. We further investigated whether DMA’s effect on cytokine expression involves the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. DMA (10 mM) significantly inhibited degradation of nuclear factor of kappa light polypeptide gene enhancer in B cell inhibitor α (IκBα) in LPS-stimulated RAW 264.7 cells, but there was no significant change in the expression of phosphorylated or native forms of downstream proteins in the MAPK pathway. In addition, DMA significantly attenuated luciferase activity in cells co-transfected with NF-κB-Luc reporter plasmid, but not with AP-1-Luc or CEBP-Luc reporters. Overall, our findings suggest that the antiinflammatory activity of DMA is mediated by inhibition of the NF-κB pathway via decreased IκBα degradation. PMID:27782292

  4. A mechanism of virulence: virulent Mycobacterium tuberculosis strain H37Rv, but not attenuated H37Ra, causes significant mitochondrial inner membrane disruption in macrophages leading to necrosis.

    PubMed

    Chen, Minjian; Gan, Huixian; Remold, Heinz G

    2006-03-15

    Infection of human monocyte-derived macrophages with Mycobacterium tuberculosis at low multiplicities of infection leads 48-72 h after the infection to cell death with the characteristics of apoptosis or necrosis. Predominant induction of one or the other cell death modality depends on differences in mitochondrial membrane perturbation induced by attenuated and virulent strains. Infection of macrophages with the attenuated H37Ra or the virulent H37Rv causes mitochondrial outer membrane permeabilization characterized by cytochrome c release from the mitochondrial intermembrane space and apoptosis. Mitochondrial outer membrane permeabilization is transient, peaks 6 h after infection, and requires Ca(2+) flux and B cell chronic lymphocytic leukemia/lymphoma 2-associated protein X translocation into mitochondria. In contrast, only the virulent H37Rv induces significant mitochondrial transmembrane potential (Deltapsi(m)) loss caused by mitochondrial permeability transition. Dissipation of Deltapsi(m) also peaks at 6 h after infection, is transient, is inhibited by the classical mitochondrial permeability transition inhibitor cyclosporine A, has a requirement for mitochondrial Ca(2+) loading, and is independent of B cell chronic lymphocytic leukemia/lymphoma translocation into the mitochondria. Transient dissipation of Deltapsi(m) 6 h after infection is essential for the induction of macrophage necrosis by Mtb, a mechanism that allows further dissemination of the pathogen and development of the disease.

  5. Comparison of intramuscular and subcutaneous administration of a herpes zoster live-attenuated vaccine in adults aged ≥50 years: a randomised non-inferiority clinical trial.

    PubMed

    Diez-Domingo, Javier; Weinke, Thomas; Garcia de Lomas, Juan; Meyer, Claudius U; Bertrand, Isabelle; Eymin, Cécile; Thomas, Stéphane; Sadorge, Christine

    2015-02-04

    Zostavax(®) is a live, attenuated varicella zoster virus (VZV) vaccine developed specifically for the prevention of HZ and PHN in individuals aged ≥50 years. During the clinical development of Zostavax, which was mainly in the US, the vaccine was administrated by the subcutaneous (SC) route. In Europe, many healthcare professionals prefer administering vaccines by the intramuscular (IM) route. This was an open-label, randomised trial conducted in 354 subjects aged ≥50 years. The primary objectives were to demonstrate that IM administration is both non-inferior to SC administration in terms of 4-week post-vaccination geometric mean titres (GMTs), and elicits an acceptable geometric mean fold-rise (GMFR) of antibody titres measured by glycoprotein enzyme-linked immunosorbent assay. Pre-specified non-inferiority was set as the lower bound of the 95% confidence interval (CI) of the GMT ratio (IM/SC) being >0.67. An acceptable GMFR for the IM route was pre-specified as the lower bound of its 95% CI being >1.4. Description of the VZV immune response using the interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT) assay and of the safety were secondary objectives. Participants were randomised to IM or SC administration (1:1). The baseline demographics were comparable between groups; mean age: 62.6 years (range: 50.0-90.5). The primary immunogenicity objectives were met (per protocol analysis): GMT ratio (IM/SC): 1.05 (95% CI: 0.93-1.18); GMFR: 2.7 (2.4-3.0). VZV immune response using IFN-γ ELISPOT were comparable between groups. Frequencies of systemic adverse events were comparable between groups. Injection-site reactions were less frequent with IM than SC route: erythema (15.9% versus 52.5%), pain (25.6% versus 39.5%) and swelling (13.6% versus 37.3%), respectively. In adults aged ≥50 years, IM administration of Zostavax elicited similar immune responses to SC administration and was well tolerated, with fewer injection-site reactions than with SC

  6. Combined administration of captopril with an antihypertensive Val-Tyr di-peptide to spontaneously hypertensive rats attenuates the blood pressure lowering effect.

    PubMed

    Matsui, Toshiro; Zhu, Xiao Lin; Watanabe, Keisuke; Tanaka, Keisuke; Kusano, Yoko; Matsumoto, Kiyoshi

    2006-11-25

    Some di-peptides have been proven to exert an antihypertensive effect in mild-hypertensive subjects. The aim of this study was to clarify whether combined administration of an ACE inhibitor, captopril, with an antihypertensive di-peptide Val-Tyr (VY) would alter their potent antihypertensive effects in spontaneously hypertensive rats (SHRs). Single oral administration of captopril (2.5 mg/kg), VY (25 mg/kg), or captopril (2.5 mg/kg)+VY (25 mg/kg) to 18-week-old male SHRs was performed. Systolic blood pressure (SBP) was measured up to 9 h, and plasma captopril concentrations were determined. A transport study of captopril and/or VY across living rat jejunum from SHRs was also performed to evaluate the kinetics of absorption. Combined administration of captopril with VY failed to lower the BP during the 9-h experiment. A transport study of captopril or VY revealed that VY inhibited captopril transport, and vice versa, in a competitive manner and exhibited an approximately 1/3-fold lower Ki value for captopril compared with that for VY; indicating that both compounds compete for the same membrane transport pathway. A 50% decrease in plasma captopril levels by combined administration with VY supported that the attenuation of the BP lowering effect was due to inhibition of captopril uptake by VY. Consequently, our findings suggest that subjects treated with ACE inhibitors for hypertension should avoid combined-intake with antihypertensive foods that are rich in small peptides due to the competitive inhibition of drug uptake by these peptides.

  7. Attenuation of systemic morphine-induced analgesia by central administration of ghrelin and related peptides in mice.

    PubMed

    Zeng, Ping; Chen, Jia-Xiang; Yang, Bei; Zhi, Xing; Guo, Fa-Xian; Sun, Meng-Li; Wang, Jing-Lei; Wei, Jie

    2013-12-01

    Ghrelin, an acylated 28-amino peptide secreted in the gastric endocrine cells, has been demonstrated to stimulate the release of growth hormone, increase food intake, and inhibit pro-inflammatory cascade, etc. Ghrelin mainly combines with its receptor (GHS-R1α) to play the role in physiological and pathological functions. It has been reported that ghrelin plays important roles in the control of pain through interaction with the opioid system in inflammatory pain and acute pain. However, very few studies show the effect of supraspinal ghrelin system on antinociception induced by intraperitoneal (i.p.) administration of morphine. In the present study, intracerebroventricular (i.c.v.) injection of ghrelin (0.1, 1, 10 and 100 nmol/L) produced inhibition of systemic morphine (6 mg/kg, i.p.) analgesia in the tail withdrawal test. Similarly, i.c.v. injection GHRP-6 and GHRP-2 which are the agonists of GHS-R1α, also decreased analgesia effect induced by morphine injected intraperitoneally in mice. Furthermore, these anti-opioid activities of ghrelin and related peptides were not blocked by pretreatment with the GHS-R1α selective antagonist [d-Lys(3)]-GHRP-6 (100 nmol/L, i.c.v.). These results demonstrated that central ghrelin and related peptides could inhibit the analgesia effect induced by intraperitoneal (i.p.) administration of morphine. The anti-opioid effects of ghrelin and related peptides do not interact with GHS-R1a. These findings may pave the way for a new strategy on investigating the interaction between ghrelin system and opioids on pain modulation.

  8. Supplemental choline does not attenuate the effects of neonatal ethanol administration on habituation of the heart rate orienting response in rats.

    PubMed

    Hunt, Pamela S; Jacobson, Sarah E; Kim, Sarah

    2014-01-01

    Several studies using rodent subjects have now shown that extra dietary choline may prevent or even reverse the deleterious effects of pre- and early post-natal ethanol administration. Choline supplementation has been shown to attenuate many, although not all, of ethanol's effects on brain development and behavior. Our laboratory has consistently reported impaired habituation of the heart rate orienting response to a novel olfactory stimulus in animals exposed to ethanol on postnatal days (PD) 4-9. Here we examine whether supplemental choline given both during and after ethanol administration could alleviate these ethanol-induced deficits. Subjects were given 5g/kg/day ethanol or sham intubations on PD 4-9. Half of the subjects in each group were given a single daily s.c. injection of choline chloride on PD 4-20, while the other half were injected daily with saline. Pups were tested for heart rate orienting and response habituation in a single test session on PD 23. Results replicated the ethanol-induced impairment in response habituation. However, choline supplementation had no effect on orienting or habituation in either neonatal treatment group. These findings indicate that habituation deficits induced by ethanol are not alleviated by extra dietary choline using these parameters. Choline holds great promise as a treatment for some fetal alcohol effects, but is not an effective treatment for all ethanol-related deficits.

  9. In vivo priming and ex vivo activation of equine neutrophils in black walnut extract-induced equine laminitis is not attenuated by systemic lidocaine administration.

    PubMed

    Loftus, John P; Williams, Jarred M; Belknap, James K; Black, Samuel J

    2010-11-15

    Laminitis is a crippling disease of horses characterized by an inflammatory response in the tissue that suspends the axial skeleton within the hoof. Pain is a common feature of laminitic pathology and its management is an important component of the treatment regime for this disease. Systemic lidocaine administration is commonly utilized to manage pain in equine laminitis; however, the potential anti-inflammatory effects of this drug during the treatment of equine laminitis have not been investigated. Here, we sought to determine if lidocaine concentrations achieved in the plasma (therapeutic concentrations) of horses systemically administered lidocaine are capable of attenuating neutrophil activation and associated inflammation. To identify markers of activation, purified neutrophils were stimulated in vitro with LPS or recombinant equine IL-8 (reqIL-8) and surface expression of CD13 and CD18 was ascertained by immunofluorescent staining. Activation with LPS or reqIL-8 in vitro induced an elevated expression of CD13 as well as a putative conformational change in CD18 detected by elevated staining with a sub-saturating concentration of anti-CD18 mAb. Lidocaine attenuated the activation-induced changes in CD13 and CD18 expression only when used at 30-70 times therapeutic concentrations. For in vivo analyses, horses were administered black walnut extract (BWE) to induce laminitis and either systemic lidocaine (n=6) or saline (n=6) as a control. Whole blood was collected and incubated with or without reqIL-8. Following which, leukocytes were stained for CD13 and CD18. Protein was extracted from laminar tissue and subjected to gelatin zymography to measure matrix metalloproteinase-9 (MMP-9) accumulation. Results obtained show that changes in neutrophil size, granularity/complexity, CD13 surface expression and CD18 staining intensity occurred over time post BWE administration irrespective of lidocaine treatment in response to incubation alone or with 100 ng/ml of reqIL-8

  10. Central blockade of melanocortin receptors attenuates the metabolic and locomotor responses to peripheral interleukin-1beta administration.

    PubMed

    Whitaker, Keith W; Reyes, Teresa M

    2008-03-01

    Loss of appetite and cachexia is an obstacle in the treatment of chronic infection and cancer. Proinflammatory cytokines released from activated immune cells and acting in the central nervous system (CNS) are prime candidates for mediating these metabolic changes, potentially affecting both energy intake as well as energy expenditure. The effect of intravenous administration of two proinflammatory cytokines, interleukin (IL)-1beta (15 microg/kg) and tumor necrosis factor (TNF)-alpha (10 microg/kg), on food and water intake, locomotor activity, oxygen consumption (VO2), and respiratory exchange ratio (RER) was evaluated. The two cytokines elicited a comparable decrease in food intake and activated similar numbers of cells in the paraventricular nucleus of the hypothalamus (PVH), a region that plays a critical role in the regulation of appetite and metabolism (determined via expression of the immediate early gene, c-fos). However, only IL-1beta reduced locomotion and RER, and increased VO2, while TNF-alpha was without effect. To examine the role of the melanocortins in mediating IL-1beta- induced metabolic changes, animals were pretreated centrally with a melanocortin receptor antagonist, HS014. Pretreatment with HS014 blocked the effect of IL-1beta on food intake and RER at later time points (beyond 8 h post injection), as well as the hypoactivity and increased metabolic rate. Further, HS014 blocked the induction of Fos-ir in the PVH. These data highlight the importance of the melanocortin system, particularly within the PVH, in mediating a broad range of metabolic responses to IL-1beta.

  11. Chronic administration of [Pyr(1)] apelin-13 attenuates neuropathic pain after compression spinal cord injury in rats.

    PubMed

    Hajimashhadi, Zahra; Aboutaleb, Nahid; Nasirinezhad, Farinaz

    2017-02-01

    Apelin is an endogenous ligand for apelin receptor (APJ) with analgesic effect on visceral, analgesic and proanalgesic influences on acute pains in animal models. The purpose of this study was to determine the possible analgesic effects of [Pyr(1)] apelin-13 on chronic pain after spinal cord injury (SCI) in rats. Animals were randomly divided into three major groups as intact, sham and SCI. The SCI group randomly allocated to four subgroups as no treatment, vehicle-treatment (normal saline: 10μl, intrathecally) and two subgroups with intrathecal injection (i.t) of 1μg and 5μg of [Pyr(1)] apelin-13. After laminectomy at T6-T8 level, spinal cord compression injury was induced using an aneurysm clip. Vehicle or [Pyr(1)] apelin-13 injected from day1 post SCI and continued for a week on a daily basis. Pain behaviors and locomotor activity were monitored up to 8weeks. At the end of the experiments, intracardial paraformaldehyde perfusion was made under deep anesthesia in some animals for histological and immunohistochemistry evaluations. Western blot technique was also done to detect caspase-3 in fresh spinal cord tissues. SCI decreased nociceptive thresholds and locomotor scores. Administration of [Pyr(1)] apelin-13 (1μg and 5μg) improved locomotor activity and reduced pain symptoms, cavity size and caspase-3 levels. Results showed long-term beneficial effects of [Pyr(1)] apelin-13 on neuropathic pain and locomotion. Therefore, we may suggest [Pyr(1)] apelin-13 as a new option for further neuropathic pain research and a suitable candidate for ensuing clinical trials in spinal cord injury arena.

  12. miR-509-3p is clinically significant and strongly attenuates cellular migration and multi-cellular spheroids in ovarian cancer

    PubMed Central

    Pedersen, Lykke; Lim, Emilia; Hernandez-Herrera, Anadulce; Rowat, Amy C.; Patil, Sagar L.; Chan, Clara K.; Wen, Yunfei; Zhang, Xinna; Basu-Roy, Upal; Mansukhani, Alka; Chu, Andy; Sipahimalani, Payal; Bowlby, Reanne; Brooks, Denise; Thiessen, Nina; Coarfa, Cristian; Ma, Yussanne; Moore, Richard A.; Schein, Jacquie E.; Mungall, Andrew J.; Liu, Jinsong; Pecot, Chad V.; Sood, Anil K.; Jones, Steven J.M.; Marra, Marco A.; Gunaratne, Preethi H.

    2016-01-01

    Ovarian cancer presents as an aggressive, advanced stage cancer with widespread metastases that depend primarily on multicellular spheroids in the peritoneal fluid. To identify new druggable pathways related to metastatic progression and spheroid formation, we integrated microRNA and mRNA sequencing data from 293 tumors from The Cancer Genome Atlas (TCGA) ovarian cancer cohort. We identified miR-509-3p as a clinically significant microRNA that is more abundant in patients with favorable survival in both the TCGA cohort (P = 2.3E–3), and, by in situ hybridization (ISH), in an independent cohort of 157 tumors (P < 1.0E–3). We found that miR-509-3p attenuated migration and disrupted multi-cellular spheroids in HEYA8, OVCAR8, SKOV3, OVCAR3, OVCAR4 and OVCAR5 cell lines. Consistent with disrupted spheroid formation, in TCGA data miR-509-3p's most strongly anti-correlated predicted targets were enriched in components of the extracellular matrix (ECM). We validated the Hippo pathway effector YAP1 as a direct miR-509-3p target. We showed that siRNA to YAP1 replicated 90% of miR-509-3p-mediated migration attenuation in OVCAR8, which contained high levels of YAP1 protein, but not in the other cell lines, in which levels of this protein were moderate to low. Our data suggest that the miR-509-3p/YAP1 axis may be a new druggable target in cancers with high YAP1, and we propose that therapeutically targeting the miR-509-3p/YAP1/ECM axis may disrupt early steps in multi-cellular spheroid formation, and so inhibit metastasis in epithelial ovarian cancer and potentially in other cancers. PMID:27036018

  13. Intracerebroventricular administration of corticotropin-releasing factor antagonist attenuates arousal response accompanied by yawning behavior in rats.

    PubMed

    Kita, Ichiro; Kubota, Natsuko; Yanagita, Shinya; Motoki, Chiharu

    2008-03-15

    We have reported that an arousal response accompanied by yawning behavior can be evoked by electrical and chemical stimulation of the hypothalamic paraventricular nucleus (PVN) in rats, although the mechanism responsible for the arousal response accompanied by yawning evoked by PVN stimulation is still unknown. In the present study, we examined the involvement of corticotropin-releasing factor (CRF) in the arousal response during yawning induced by electrical stimulation of the PVN in anesthetized, spontaneous breathing rats using intracerebroventricular (icv) injection of alpha-helical CRF, a CRF antagonist (4.2 microg, lateral ventricle). The electrocorticogram (ECoG) was recorded to evaluate arousal responses during yawning. Fast Fourier transform was used to obtain the power spectrum in delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-20 Hz) bands. We also recorded the intercostal electromyogram as an index of inspiratory activity and blood pressure (BP) as an index of autonomic function to evaluate yawning response. PVN stimulation induced significant increases in relative powers of theta, alpha, and beta bands, but not delta band, concurrent with yawning events regardless of icv injection, though the relative powers after icv injection of alpha-helical CRF were significantly lower than those after saline injection. These findings suggest that CRF neurons in the PVN are primarily responsible for the arousal response accompanied by yawning behavior.

  14. Early administration of probiotic Lactobacillus acidophilus and/or prebiotic inulin attenuates pathogen-mediated intestinal inflammation and Smad 7 cell signaling.

    PubMed

    Foye, Ondulla T; Huang, I-Fei; Chiou, Christine C; Walker, W Allan; Shi, Hai Ning

    2012-08-01

    Immaturity of gut-associated immunity may contribute to pediatric mortality associated with enteric infections. A murine model to parallel infantile enteric disease was used to determine the effects of probiotic, Lactobacillus acidophilus (La), prebiotic, inulin, or both (synbiotic, syn) on pathogen-induced inflammatory responses, NF-κB, and Smad 7 signaling. Newborn mice were inoculated bi-weekly for 4 weeks with La, inulin, or syn and challenged with Citrobacter rodentium (Cr) at 5 weeks. Mouse intestinal epithelial cells (CMT93) were exposed to Cr to determine temporal alterations in NF-Kappa B and Smad 7 levels. Mice with pretreatment of La, inulin, and syn show reduced intestinal inflammation following Cr infection compared with controls, which is associated with significantly reduced bacterial colonization in La, inulin, and syn animals. Our results further show that host defense against Cr infection correlated with enhanced colonic IL-10 and transforming growth factor-β expression and inhibition of NF-κB in syn-treated mice, whereas mice pretreated with syn, La, or inulin had attenuation of Cr-induced Smad 7 expression. There was a temporal Smad 7 and NF-κB intracellular accumulation post-Cr infection and post-tumor necrosis factor stimulation in CMT93 cells. These results, therefore, suggest that probiotic, La, prebiotic inulin, or synbiotic may promote host-protective immunity and attenuate Cr-induced intestinal inflammation through mechanisms affecting NF-κB and Smad 7 signaling.

  15. Chronic Carbamazepine Administration Attenuates Dopamine D2-like Receptor-Initiated Signaling via Arachidonic Acid in Rat Brain

    PubMed Central

    Chang, Lisa; Chen, Mei; Bell, Jane M.; Rapoport, Stanley I.

    2016-01-01

    Observations that dopaminergic antagonists are beneficial in bipolar disorder and that dopaminergic agonists can produce mania suggest that bipolar disorder involves excessive dopaminergic transmission. Thus, mood stabilizers used to treat the disease might act in part by downregulating dopaminergic transmission. In agreement, we reported that dopamine D2-like receptor mediated signaling involving arachidonic acid (AA, 20:4n-6) was downregulated in rats chronically treated with lithium. To see whether chronic carbamazepine, another mood stabilizer, did this as well, we injected i.p. saline or the D2-like receptor agonist, quinpirole (1 mg/kg), into unanesthetized rats that had been pretreated for 30 days with i.p. carbamazepine (25 mg/kg/day) or vehicle, and used quantitative autoradiography to measure regional brain incorporation coefficients (k*) for AA, markers of signaling. We also measured brain prostaglandin E2 (PGE2), an AA metabolite. In vehicle-treated rats, quinpirole compared with saline significantly increased k* for AA in 35 of 82 brain regions examined, as well as brain PGE2 concentration. Affected regions belong to dopaminergic circuits and have high D2-like receptor densities. Chronic carbamazepine pretreatment prevented the quinpirole-induced increments in k* and in PGE2. These findings are consistent with the hypothesis that effective mood stabilizers generally downregulate brain AA signaling via D2-like receptors, and that this signaling is upregulated in bipolar disorder. PMID:18302021

  16. Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle

    PubMed Central

    Sakellariou, Giorgos K.; Pearson, Timothy; Lightfoot, Adam P.; Nye, Gareth A.; Wells, Nicola; Giakoumaki, Ifigeneia I.; Griffiths, Richard D.; McArdle, Anne; Jackson, Malcolm J.

    2016-01-01

    Age-related skeletal muscle dysfunction is the underlying cause of morbidity that affects up to half the population aged 80 and over. Considerable evidence indicates that oxidative damage and mitochondrial dysfunction contribute to the sarcopenic phenotype that occurs with aging. To examine this, we administered the mitochondria-targeted antioxidant mitoquinone mesylate {[10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl] triphenylphosphonium; 100 μM} to wild-type C57BL/6 mice for 15 wk (from 24 to 28 mo of age) and investigated the effects on age-related loss of muscle mass and function, changes in redox homeostasis, and mitochondrial organelle integrity and function. We found that mitoquinone mesylate treatment failed to prevent age-dependent loss of skeletal muscle mass associated with myofiber atrophy or alter a variety of in situ and ex vivo muscle function analyses, including maximum isometric tetanic force, decline in force after a tetanic fatiguing protocol, and single-fiber-specific force. We also found evidence that long-term mitoquinone mesylate administration did not reduce mitochondrial reactive oxygen species or induce significant changes in muscle redox homeostasis, as assessed by changes in 4-hydroxynonenal protein adducts, protein carbonyl content, protein nitration, and DNA damage determined by the content of 8-hydroxydeoxyguanosine. Mitochondrial membrane potential, abundance, and respiration assessed in permeabilized myofibers were not significantly altered in response to mitoquinone mesylate treatment. Collectively, these findings demonstrate that long-term mitochondria-targeted mitoquinone mesylate administration failed to attenuate age-related oxidative damage in skeletal muscle of old mice or provide any protective effect in the context of muscle aging.—Sakellariou, G. K., Pearson, T., Lightfoot, A. P., Nye, G. A., Wells, N., Giakoumaki, I. I., Griffiths, R. D., McArdle, A., Jackson, M. J. Long-term administration of the

  17. Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle.

    PubMed

    Sakellariou, Giorgos K; Pearson, Timothy; Lightfoot, Adam P; Nye, Gareth A; Wells, Nicola; Giakoumaki, Ifigeneia I; Griffiths, Richard D; McArdle, Anne; Jackson, Malcolm J

    2016-11-01

    Age-related skeletal muscle dysfunction is the underlying cause of morbidity that affects up to half the population aged 80 and over. Considerable evidence indicates that oxidative damage and mitochondrial dysfunction contribute to the sarcopenic phenotype that occurs with aging. To examine this, we administered the mitochondria-targeted antioxidant mitoquinone mesylate {[10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl] triphenylphosphonium; 100 μM} to wild-type C57BL/6 mice for 15 wk (from 24 to 28 mo of age) and investigated the effects on age-related loss of muscle mass and function, changes in redox homeostasis, and mitochondrial organelle integrity and function. We found that mitoquinone mesylate treatment failed to prevent age-dependent loss of skeletal muscle mass associated with myofiber atrophy or alter a variety of in situ and ex vivo muscle function analyses, including maximum isometric tetanic force, decline in force after a tetanic fatiguing protocol, and single-fiber-specific force. We also found evidence that long-term mitoquinone mesylate administration did not reduce mitochondrial reactive oxygen species or induce significant changes in muscle redox homeostasis, as assessed by changes in 4-hydroxynonenal protein adducts, protein carbonyl content, protein nitration, and DNA damage determined by the content of 8-hydroxydeoxyguanosine. Mitochondrial membrane potential, abundance, and respiration assessed in permeabilized myofibers were not significantly altered in response to mitoquinone mesylate treatment. Collectively, these findings demonstrate that long-term mitochondria-targeted mitoquinone mesylate administration failed to attenuate age-related oxidative damage in skeletal muscle of old mice or provide any protective effect in the context of muscle aging.-Sakellariou, G. K., Pearson, T., Lightfoot, A. P., Nye, G. A., Wells, N., Giakoumaki, I. I., Griffiths, R. D., McArdle, A., Jackson, M. J. Long-term administration of the

  18. Oral administration of paeoniflorin attenuates allergic contact dermatitis by inhibiting dendritic cell migration and Th1 and Th17 differentiation in a mouse model.

    PubMed

    Shi, Dongmei; Li, Xuefeng; Li, Dongmei; Zhao, Quanjing; Shen, Yongnian; Yan, Hongxia; Fu, Hongjun; Zheng, Hailin; Lu, Guixia; Qiu, Ying; Liu, Weida

    2015-04-01

    Allergic contact dermatitis (ACD) is a hapten-specific CD4(+) T-cells mediated inflammatory response of the skin. Its pathomechanism involves 2 phases, an induction phase and an elicitation phase. Langerhans cells (LCs) and dendritic cells (DCs) in the skin play key roles in presenting low molecular weight chemicals (haptens) to the lymph nodes. Therefore, inhibition of the migration of LCs or DCs and T-cell proliferation is each expected to control ACD disease. To explore the effectiveness of paeoniflorin (PF) on the migration of LCs and T-cell proliferation in vivo, we establish a murine model of ACD, promoted by repeated exposure to an allergen (specifically 1-Chloro-2,4-dinitrobenzene (DNCB)). Administration of PF inhibits DC migration in this DNCB-induced model in the induction phase. As a result, epidermal LC density in the elicitation phase increased in PF-treated mice when compared to PF-untreated mice. At the same time, PF reduced IFN-γ(+)CD4(+) and IL-17(+)CD4(+) T cells proliferation (but not IL-4(+)CD4(+) T cells proliferation), leading to an attenuated cutaneous inflammatory response. Consistent with this T-cell proliferation profile, secretions of IFN-γ and IL-17 were reduced and IL-10 secretion increased in PF-treated mice, but production of IL-4 and IL-5 remained unchanged in the skin and blood samples. These results suggest that oral administration of PF can treat and prevent ACD effectively through inhibition of DC migration, and thus decrease the capacity of DCs to stimulate Th1 and Th17 cell differentiation and cytokine production.

  19. Rest and stress transluminal attenuation gradient and contrast opacification difference for detection of hemodynamically significant stenoses in patients with suspected coronary artery disease.

    PubMed

    Ko, Brian S; Seneviratne, Sujith; Cameron, James D; Gutman, Sarah; Crossett, Marcus; Munnur, Kiran; Meredith, Ian T; Wong, Dennis T L

    2016-07-01

    This study evaluated the feasibility of stress 320 detector CT coronary angiography (CTA) derived transluminal attenuation gradient (TAG320) and contrast opacification (CO) difference to detect hemodynamically significant stenoses as determined by invasive fractional flow reserve (FFR ≤ 0.80). Twenty-seven patients, including 51 vessels on rest CTA were studied. 16 (31 %) vessels were not interpretable on stress CTA largely secondary to motion artefacts. Receiver operating characteristic curve analysis showed a comparable area under the curve (AUC) for rest and stress TAG320 (0.78 and 0.75) which was higher than CTA alone (0.68), and rest and stress CO difference (0.76 and 0.67). Compared with rest CTA, stress CTA demonstrated inferior image quality (Median Likert score 4 vs. 3, P < 0.0001) and required a higher mean radiation exposure (3.2 vs. 5.1 mSv, P < 0.0001). Stress TAG320 and CO difference is less feasible and was not superior in diagnostic performance when compared with rest TAG320 and CO difference.

  20. Peripheral administration of the selective inhibitor of soluble Tumor Necrosis Factor (TNF) XPro®1595 attenuates nigral cell loss and glial activation in 6-OHDA hemiparkinsonian rats

    PubMed Central

    Barnum, Christopher J.; Chen, Xi; Chung, Jaegwon; Chang, Jianjun; Williams, Martha; Grigoryan, Nelly; Tesi, Raymond J.; Tansey, Malú G.

    2014-01-01

    BACKGROUND Parkinson's disease (PD) is a complex multi-system age-related neurodegenerative disorder. Targeting the ongoing neuroinflammation in PD patients is one strategy postulated to slow down or halt disease progression. Proof-of-concept studies from our group demonstrated that selective inhibition of soluble Tumor Necrosis Factor (solTNF) by intranigral delivery of dominant negative TNF (DN-TNF) inhibitors reduced neuroinflammation and nigral dopamine (DA) neuron loss in endotoxin and neurotoxin rat models of nigral degeneration. OBJECTIVE As a next step toward human clinical trials, we aimed to determine the extent to which peripherally administered DN-TNF inhibitor XPro®1595 could: i) cross the blood-brain-barrier in therapeutically relevant concentrations, ii) attenuate neuroinflammation (microglia and astrocyte), and iii) mitigate loss of nigral DA neurons in rats receiving a unilateral 6-hydroxydopamine (6-OHDA) striatal lesion. METHODS Rats received unilateral 6-OHDA (20 μg into the right striatum). Three or 14 days after lesion, rats were dosed with XPro®1595 (10 mg/kg in saline, subcutaneous) every third day for 35 days. Forelimb asymmetry was used to assess motor deficits after the lesion; brains were harvested 35 days after the lesion for analysis of XPro®1595 levels, glial activation, and nigral DA neuron number. RESULTS Peripheral subcutaneous dosing of XPro®1595 achieved plasma levels of 1–8 μg/mL and CSF levels of 1–6 ng/mL depending on the time the rats were killed after final XPro®1595 injection. Irrespective of start date, XPro®1595 significantly reduced microglia and astrocyte number in SNpc whereas loss of nigral DA neurons was attenuated when drug was started 3, but not 14 days after the 6-OHDA lesion. CONCLUSIONS Our data suggest that systemically administered XPro®1595 may have disease-modifying potential in PD patients where inflammation is part of their pathology. PMID:25061061

  1. Intraarterial administration of norcantharidin attenuates ischemic stroke damage in rodents when given at the time of reperfusion: novel uses of endovascular capabilities

    PubMed Central

    Khan, Imad S.; Odom, Mitchell; Ehtesham, Moneeb; Colvin, Daniel; Quarles, C. Chad; McLaughlin, BethAnn; Singer, Robert J.

    2016-01-01

    OBJECTIVE Matrix metalloprotease-9 (MMP-9) plays a critical role in infarct progression, blood-brain barrier (BBB) disruption, and vasogenic edema. While systemic administration of MMP-9 inhibitors has shown neuroprotective promise in ischemic stroke, there has been little effort to incorporate these drugs into endovascular modalities. By modifying the rodent middle cerebral artery occlusion (MCAO) model to allow local intraarterial delivery of drugs, one has the ability to mimic endovascular delivery of therapeutics. Using this model, the authors sought to maximize the protective potential of MMP-9 inhibition by intraarterial administration of an MMP-9 inhibitor, norcantharidin (NCTD). METHODS Spontaneously hypertensive rats were subjected to 90-minute MCAO followed immediately by local intraarterial administration of NCTD. The rats’ neurobehavioral performances were scored according to the ladder rung walking test results and the Garcia neurological test for as long as 7 days after stroke. MRI was also conducted 24 hours after the stroke to assess infarct volume and BBB disruption. At the end of the experimental protocol, rat brains were used for active MMP-9 immunohistochemical analysis to assess the degree of MMP-9 inhibition. RESULTS NCTD-treated rats showed significantly better neurobehavioral scores for all days tested. MR images also depicted significantly decreased infarct volumes and BBB disruption 24 hours after stroke. Inhibition of MMP-9 expression in the ischemic region was depicted on immunohistochemical analysis, wherein treated rats showed decreased active MMP-9 staining compared with controls. CONCLUSIONS Intraarterial NCTD significantly improved outcome when administered at the time of reperfusion in a spontaneously hypertensive rat stroke model. This study suggests that supplementing endovascular revascularization with local neuroprotective drug therapy may be a viable therapeutic strategy. PMID:26544777

  2. Chronic running wheel activity attenuates the antinociceptive actions of morphine and morphine-6-glucouronide administration into the periaqueductal gray in rats.

    PubMed

    Mathes, Wendy Foulds; Kanarek, Robin B

    2006-04-01

    Chronic exercise in a running wheel increases baseline pain sensitivity while attenuating the antinociceptive effects of peripherally administered opiate agonists in laboratory rodents. To determine if these effects are due to exercise-induced changes in the central nervous system (CNS) or an artifact of exercise-induced alterations in peripheral physiology, the present study evaluated the antinociceptive actions of centrally administered opiate agonists in active and inactive female rats. Rats were implanted with cannula into the right periaqueductal gray (PAG) area of the midbrain. After the completion of the surgery, the animals were allowed ad libitum access to running wheels or housed in standard cages for three weeks. Pain sensitivity was measured on the tail flick test before and immediately following microinjections of either morphine (0, 2.5, 5.0, 10.0, 20.0 microg/rat) or the more potent morphine metabolite, morphine-6-glucuronide (M6G) (0, 0.03, 0.1, 0.3, 1.0 microg/rat). Baseline tail flick latencies were significantly shorter in active than in inactive rats. Additionally, active animals were less sensitive to the antinociceptive effects of morphine and M6G than inactive rats. These findings provide evidence for the involvement of the CNS in exercise-mediated alterations in pain sensitivity and opiate drug actions.

  3. Prenatal administration of the cytochrome P4501A inducer, {Beta}-naphthoflavone (BNF), attenuates hyperoxic lung injury in newborn mice: Implications for bronchopulmonary dysplasia (BPD) in premature infants

    SciTech Connect

    Couroucli, Xanthi I.; Liang Yanhong Wei; Jiang Weiwu; Wang Lihua; Barrios, Roberto; Yang Peiying; Moorthy, Bhagavatula

    2011-10-15

    Supplemental oxygen contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. In this investigation, we tested the hypothesis that prenatal treatment of pregnant mice (C57BL/6J) with the cytochrome P450 (CYP)1A1 inducer, ss-napthoflavone (BNF), will lead to attenuation of lung injury in newborns (delivered from these dams) exposed to hyperoxia by mechanisms entailing transplacental induction of hepatic and pulmonary CYP1A enzymes. Pregnant mice were administered the vehicle corn oil (CO) or BNF (40 mg/kg), i.p., once daily for 3 days on gestational days (17-19), and newborns delivered from the mothers were either maintained in room air or exposed to hyperoxia (> 95% O{sub 2}) for 1-5 days. After 3-5 days of hyperoxia, the lungs of CO-treated mice showed neutrophil infiltration, pulmonary edema, and perivascular inflammation. On the other hand, BNF-pretreated neonatal mice showed decreased susceptibility to hyperoxic lung injury. These mice displayed marked induction of ethoxyresorufin O-deethylase (EROD) (CYP1A1) and methoxyresorufin O-demethylase (MROD) (CYP1A2) activities, and levels of the corresponding apoproteins and mRNA levels until PND 3 in liver, while CYP1A1 expression alone was augmented in the lung. Prenatal BNF did not significantly alter gene expression of pulmonary NAD(P)H quinone reductase (NQO1). Hyperoxia for 24-72 h resulted in increased pulmonary levels of the F{sub 2}-isoprostane 8-iso-PGF{sub 2{alpha}}, whose levels were decreased in mice prenatally exposed to BNF. In conclusion, our results suggest that prenatal BNF protects newborns against hyperoxic lung injury, presumably by detoxification of lipid hydroperoxides by CYP1A enzymes, a phenomenon that has implications for prevention of BPD in infants. - Highlights: > Supplemental oxygen is routinely administered to premature infants. > Hyperoxia causes lung injury in experimental animals. > Prenatal treatment of mice with beta-naphthoflavone attenuates oxygen

  4. Annual committee reports on significant legislative, judicial and administrative developments in 1983: Public Lands and Land-Use Committee

    SciTech Connect

    Not Available

    1984-01-01

    The Supreme Court made three major land-use decisions during 1983, two dealing with federalism and the third with federal jiduciary obligation. The US Forest Service Small Tracts Act added flexibility to the disposal of small tracts. Court cases relating to national forests dealt with title disputes, oil and gas leasing, Indian religious practices, dual permitting under the Wilderness Act, and licensing hydro projects on Indian lands. The committee reports uneven administrative progress by the Forests Service in managing the forests. Legislation relating to Department of Interior Management Lands focuses on Outer Continental Shelf and federal coal leases and wilderness areas. The Supreme Court made several decisions involving the classification of sand and gravel as minerals, trespass, nonimpairment standards, herbicides, and other issues. 132 references.

  5. Attenuation of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity by resveratrol: a comparative study with different routes of administration.

    PubMed

    Ishida, Takumi; Takeda, Tomoki; Koga, Takayuki; Yahata, Masahiro; Ike, Ayako; Kuramoto, Chihiro; Taketoh, Junko; Hashiguchi, Isamu; Akamine, Akifumi; Ishii, Yuji; Yamada, Hideyuki

    2009-05-01

    The activation of aryl hydrocarbon receptor with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to be antagonized by co-treatment with resveratrol. However, such a protective effect has been suggested from studies using subcutaneous injection of this polyphenol. To evaluate the practical usefulness of resveratrol, this study examined the protective effect of oral resveratrol on the sub-acute toxic effects of TCDD in C57BL/6J mice. A TCDD-induced wasting syndrome was not alleviated by treating mice for 28 d with oral resveratrol. However, subcutaneous injection of resveratrol for 5 d significantly improved the symptoms. Neither oral nor subcutaneous administration of resveratrol alleviated TCDD-induced hepatomegaly and thymic atrophy. Steatosis produced by TCDD was markedly counteracted by co-treatment with oral resveratrol, whereas resveratrol injected subcutaneously had no effect. The reason for the lack of protective effect via the latter dosing route was assumed to be due to the minor accumulation of hepatic lipids 5 d after TCDD treatment. To clarify the mechanisms, the activity of ethoxyresorufin O-deethylase and the content of thiobarbituric acid-reactive substances in the liver were measured. Both indices increased by TCDD treatment were significantly suppressed by subcutaneous injection of resveratrol. In contrast, oral resveratrol failed to rescue them. In agreement with the greater protective effects of subcutaneously-injected resveratrol, pharmacokinetic studies indicated that the area under the curve extrapolated to infinity (AUC(infinity)) was 8.2-times greater following subcutaneous injection compared with oral administration. These data suggest that 1) oral resveratrol is attractive candidate as an agent capable of combating dioxin toxicity and 2) increasing the bioavailability of this polyphenol enhances its protective effect.

  6. Targeted therapy via oral administration of attenuated Salmonella expression plasmid-vectored Stat3-shRNA cures orthotopically transplanted mouse HCC

    PubMed Central

    Tian, Y; Guo, B; Jia, H; Ji, K; Sun, Y; Li, Y; Zhao, T; Gao, L; Meng, Y; Kalvakolanu, DV; Kopecko, DJ; Zhao, X; Zhang, L; Xu, D

    2013-01-01

    The development of RNA interference-based cancer gene therapies has been delayed due to the lack of effective tumor-targeting delivery systems. Attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) has a natural tropism for solid tumors. We report here the use of attenuated S. Typhimurium as a vector to deliver shRNA directly into tumor cells. Constitutively activated signal transducer and activator of transcription 3 (Stat3) is a key transcription factor involved in both hepatocellular carcinoma (HCC) growth and metastasis. In this study, attenuated S. Typhimurium was capable of delivering shRNA-expressing vectors to the targeted cancer cells and inducing RNA interference in vivo. More importantly, a single oral dose of attenuated S. Typhimurium carrying shRNA-expressing vectors targeting Stat3 induced remarkably delayed and reduced HCC (in 70% of mice). Cancer in these cured mice did not recur over 2 years following treatment. These data demonstrated that RNA interference combined with Salmonella as a delivery system may offer a novel clinical approach for cancer gene therapy. PMID:22555509

  7. Administration of the glial cell modulator, minocycline, in the nucleus accumbens attenuated the maintenance and reinstatement of morphine-seeking behavior.

    PubMed

    Arezoomandan, Reza; Haghparast, Abbas

    2016-03-01

    Relapse to drug use is one of the most difficult clinical problems in treating addiction. Glial activation has been linked with the drug abuse, and the glia modulators such as minocycline can modulate the drug abuse effects. The aim of the present study was to determine whether minocycline could attenuate the maintenance and reinstatement of morphine. Conditioned place preference (CPP) was induced by subcutaneous injection of morphine (5 mg/kg) for 3 days. Following the acquisition of the CPP, the rats were given daily bilateral intra-NAc injections of either minocycline (1, 5, and 10 μg/0.5 μL) or saline (0.5 μL). The animals were tested for conditioning score 60 min after each injection. To induce the reinstatement, a priming dose of morphine (1 mg/kg) was injected 1 day after the final extinction day. The morphine-induced CPP lasted for 7 days after cessation of morphine treatment. Our data revealed that a priming dose of morphine could reinstate the extinguished morphine-induced CPP. Daily intra-accumbal injection of minocycline during the extinction period blocked the maintenance of morphine CPP and also attenuated the priming-induced reinstatement. Our findings indicated that minocycline could facilitate the extinction and attenuate the reinstatement of morphine. These results provided new evidence that minocycline might be considered as a promising therapeutic agent for the treatment of several symptoms associated with morphine abuse.

  8. High Affinity Dopamine D3 Receptor (D3R)-Selective Antagonists Attenuate Heroin Self-Administration in Wild-Type but not D3R Knockout Mice

    PubMed Central

    2015-01-01

    The dopamine D3 receptor (D3R) is a promising target for the development of pharmacotherapeutics to treat substance use disorders. Several D3R-selective antagonists are effective in animal models of drug abuse, especially in models of relapse. Nevertheless, poor bioavailability, metabolic instability, and/or predicted toxicity have impeded success in translating these drug candidates to clinical use. Herein, we report a series of D3R-selective 4-phenylpiperazines with improved metabolic stability. A subset of these compounds was evaluated for D3R functional efficacy and off-target binding at selected 5-HT receptor subtypes, where significant overlap in SAR with D3R has been observed. Several high affinity D3R antagonists, including compounds 16 (Ki = 0.12 nM) and 32 (Ki = 0.35 nM), showed improved metabolic stability compared to the parent compound, PG648 (6). Notably, 16 and the classic D3R antagonist SB277011A (2) were effective in reducing self-administration of heroin in wild-type but not D3R knockout mice. PMID:26203768

  9. Nerve growth factor administration attenuates cognitive but not neurobehavioral motor dysfunction or hippocampal cell loss following fluid-percussion brain injury in rats.

    PubMed

    Sinson, G; Voddi, M; McIntosh, T K

    1995-11-01

    Lateral fluid-percussion brain injury in rats results in cognitive deficits, motor dysfunction, and selective hippocampal cell loss. Neurotrophic factors have been shown to have potential therapeutic applications in neurodegenerative diseases, and nerve growth factor (NGF) has been shown to be neuroprotective in models of excitotoxicity. This study evaluated the neuroprotective efficacy of intracerebral NGF infusion after traumatic brain injury. Male Sprague-Dawley rats received lateral fluid-percussion brain injury of moderate severity (2.1-2.3 atm). A miniosmotic pump was implanted 24 h after injury to infuse NGF (n = 34) or vehicle (n = 16) directly into the region of maximal cortical injury. Infusions of NGF continued until the animal was killed at 72 h, 1 week, or 2 weeks after injury. Animals were evaluated for cognitive dysfunction (Morris Water Maze) and regional neuronal cell loss (Nissl staining) at each of the three time points. Animals surviving for 1 or 2 weeks were also evaluated for neurobehavioral motor function. Although an improvement in memory scores was not observed at 72 h after injury, animals receiving NGF infusions showed significantly improved memory scores when tested at 1 or 2 weeks after injury compared with injured animals receiving vehicle infusions (p < 0.05). Motor scores and CA3 hippocampal cell loss were not significantly different in any group of NGF-treated animals when compared with controls. These data suggest that NGF administration, in the acute, posttraumatic period following fluid-percussion brain injury, may have potential in improving post-traumatic cognitive deficits.

  10. Angiotensin-(1-7) administration attenuates Alzheimer's disease-like neuropathology in rats with streptozotocin-induced diabetes via Mas receptor activation.

    PubMed

    Chen, Jin-Liang; Zhang, Dong-Ling; Sun, Yue; Zhao, Yu-Xing; Zhao, Ke-Xiang; Pu, Die; Xiao, Qian

    2017-03-27

    Diabetes mellitus (DM) is associated with cognitive deficits and an increased risk of Alzheimer's disease (AD). Recently, a newly identified heptapeptide of the renin-angiotensin system (RAS), angiotensin-(1-7) [Ang-(1-7)], was found to protect against brain damage. This study investigated the effects of Ang-(1-7) on diabetes-induced cognitive deficits. Sprague-Dawley rats were randomly divided into four groups. Diabetes was induced via single i.p. streptozotocin (STZ) injections. Ten weeks after diabetes induction, rats in each group received an intracerebral-ventricular (ICV) infusion of either vehicle, Ang-(1-7) alone, or Ang-(1-7)+A779 daily for two weeks. At the end of the study, Morris water maze (MWM) tests were performed to test cognitive functions before the rats were euthanized. Ang-(1-7) treatment significantly reduced escape latencies in diabetic rats in acquisition trials and markedly enhanced platform area crossing frequency and time spent in the target quadrant in probe trials (3.0±0.39 vs. 1.0±0.33, 39.39±1.11% vs. 25.62±3.07%, respectively, P<0.01). Ang-(1-7) treatment ameliorated damage to the ultrastructure of hippocampal synapses, reduced the expression of hippocampal phospho-tau at Ser396 (P<0.01), Ser404 (P<0.01) and Ser202/Thr205 (P<0.05), and decreased amyloid-β oligomer and both soluble and insoluble β-amyloid peptide 1-42 (Aβ 1-42) and Aβ 1-40 levels (P<0.01). These protective effects were significantly reversed by the co-administration of A779. These findings show that Ang-(1-7) is a promising therapeutic target for diabetes-induced cognitive impairment. The neuroprotective effects of Ang-(1-7) were mainly through Mas receptor (MasR) activation.

  11. The GLP-1 agonist exendin-4 attenuates self-administration of sweetened fat on fixed and progressive ratio schedules of reinforcement in rats.

    PubMed

    Bernosky-Smith, Kimberly A; Stanger, David B; Trujillo, Alexandria J; Mitchell, Luke R; España, Rodrigo A; Bass, Caroline E

    2016-03-01

    GLP-1 agonists such as exendin-4 (EX4) are used in the treatment of type-2 diabetes and have the additional benefit of promoting weight loss. GLP-1 agonists decrease feeding through peripheral effects, but recent evidence suggests they may also influence sweet or high fat preference, as well as motivation to obtain these tastants. Yet it remains unclear how GLP-1-induced alterations in food preference influences decreases in overall feeding. The current study sought to determine if EX4 affects the reinforcing strength and consumption of a highly palatable sweet/fat reinforcer. Rats were trained to self-administer sweetened vegetable shortening (SVS) under fixed (FR) and progressive ratio (PR) schedules of reinforcement. EX4 (0.3-2.4μg/kg, i.p.) administered one hour prior to operant sessions significantly reduced responses for SVS under both FR and PR schedules, although the lowest active dose (0.6μg/kg) significantly suppressed FR responding only. EX4 also dose dependently decreased locomotor activity (0.6-2.4μg/kg doses), but did not enhance acute kaolin intake, suggesting that nausea did not influence the self-administration results. Analysis of ED50 values show that EX4 is more effective at inhibiting FR responding versus PR, indicating that EX4 may have more potent effects on amount consumed versus motivation for SVS. Although EX4 caused generalized locomotor suppression, these results do not fully explain the decreases in operant responding. For example, a dose of EX4 (0.6μg/kg) that significantly suppressed locomotor activity did not affect the mean total number of lever presses during PR sessions (59±15), although it did significantly reduce lever presses during FR sessions (21±3). In addition, the pattern of intake was constant at the beginning of the sessions in both PR and FR schedules, regardless of the dose. Together these data suggest that EX4 inhibits consumption of a palatable high sweet/high fat reinforcer potentially through altering satiety.

  12. Administration of a PTEN inhibitor BPV(pic) attenuates early brain injury via modulating AMPA receptor subunits after subarachnoid hemorrhage in rats.

    PubMed

    Chen, Yujie; Luo, Chunxia; Zhao, Mingyue; Li, Qiang; Hu, Rong; Zhang, John H; Liu, Zhi; Feng, Hua

    2015-02-19

    The aim of this study was to investigate whether the phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibitor dipotassium bisperoxo(pyridine-2-carboxyl) oxovanadate (BPV(pic)) attenuates early brain injury by modulating α-amino-3-hydroxy-5-methyl-4-isoxa-zolep-propionate (AMPA) receptor subunits after subarachnoid hemorrhage (SAH). A standard intravascular perforation model was used to produce the experimental SAH in Sprague-Dawley rats. BPV(pic) treatment (0.2mg/kg) was evaluated for effects on neurological score, brain water content, Evans blue extravasation, hippocampal neuronal death and AMPA receptor subunits alterations after SAH. We found that BPV(pic) is effective in attenuating BBB disruption, lowering edema, reducing hippocampal neural death and improving neurological outcomes. In addition, the AMPA receptor subunit GluR1 protein expression at cytomembrane was downregulated, whereas the expression of GluR2 and GluR3 was upregulated after BPV(pic) treatment. Our results suggest that PTEN inhibited by BPV(pic) plays a neuroprotective role in SAH pathophysiology, possibly by alterations in glutamate AMPA receptor subunits.

  13. Significant increase of salivary testosterone levels after single therapeutic transdermal administration of testosterone: suitability as a potential screening parameter in doping control.

    PubMed

    Thieme, Detlef; Rautenberg, Claudia; Grosse, Joachim; Schoenfelder, Martin

    2013-01-01

    The legally defensible proof of the abuse of endogenous steroids in sports is currently based on carbon isotope ratio mass spectrometry (IRMS), i.e. a comparison between (13)C/(12)C ratios of diagnostic precursors and metabolites of testosterone. The application of this technique requires a chromatographic baseline separation of respective steroids prior to IRMS detection and hence laborious sample pre-processing of the urinary steroid extracts including clean up by solid-phase extraction and/or liquid chromatography. Consequently, an efficient pre-selection of suspicious control urine samples is essential for appropriate follow up confirmation by IRMS and effective doping control. Two single transdermal administration studies of testosterone (50 mg Testogel® and Testopatch® at 3.8 mg in 16 h, respectively) were conducted and resulting profiles of salivary testosterone and urinary steroid profiles and corresponding carbon isotope ratios were determined. Conventional doping control markers (testosterone/epitestosterone ratio, threshold concentrations of androsterone, etiocholanolone, or androstanediols) did not approach or exceed critical thresholds. In contrast to these moderate variations, the testosterone concentration in oral fluid increased from basal values (30-142 pg/mg) to peak concentrations above 1000 pg/mg. It is likely that this significant increase in oral fluid is due to a pulsatile elevation of free (protein unbound) circulating testosterone after transdermal administration and may be assumed to represent a more diagnostic marker for transdermal testosterone administration.

  14. In vivo administration of a JAK3 inhibitor during acute SIV infection leads to significant increases in viral load during chronic infection.

    PubMed

    Takahashi, Yoshiaki; Byrareddy, Siddappa N; Albrecht, Christina; Brameier, Markus; Walter, Lutz; Mayne, Ann E; Dunbar, Paul; Russo, Robert; Little, Dawn M; Villinger, Tara; Khowawisetsut, Ladawan; Pattanapanyasat, Kovit; Villinger, Francois; Ansari, Aftab A

    2014-03-01

    The studies reported herein are the first to document the effect of the in vivo administration of a JAK3 inhibitor for defining the potential role of NK cells during acute SIV infection of a group of 15 rhesus macaques (RM). An additional group of 16 MHC/KIR typed RM was included as controls. The previously optimized in vivo dose regimen (20 mg/kg daily for 35 days) led to a marked depletion of each of the major NK cell subsets both in the blood and gastro-intestinal tissues (GIT) during acute infection. While such depletion had no detectable effects on plasma viral loads during acute infection, there was a significant sustained increase in plasma viral loads during chronic infection. While the potential mechanisms that lead to such increased plasma viral loads during chronic infection remain unclear, several correlates were documented. Thus, during acute infection, the administration of the JAK3 inhibitor besides depleting all NK cell subsets also decreased some CD8⁺ T cells and inhibited the mobilization of the plasmacytoid dendritic cells in the blood and their localization to the GIT. Of interest is the finding that the administration of the JAK3 inhibitor during acute infection also resulted in the sustained maintenance during chronic infection of a high number of naïve and central memory CD4⁺ T cells, increases in B cells in the blood, but decreases in the frequencies and function of NKG2a⁺ NK cells within the GIT and blood, respectively. These data identify a unique role for JAK3 inhibitor sensitive cells, that includes NK cells during acute infection that in concert lead to high viral loads in SIV infected RM during chronic infection without affecting detectable changes in antiviral humoral/cellular responses. Identifying the precise mechanisms by which JAK3 sensitive cells exert their influence is critical with important implications for vaccine design against lentiviruses.

  15. Omega-conotoxin MVIIC attenuates neuronal apoptosis in vitro and improves significant recovery after spinal cord injury in vivo in rats

    PubMed Central

    Oliveira, Karen M; Lavor, Mário Sérgio L; Silva, Carla Maria O; Fukushima, Fabíola B; Rosado, Isabel R; Silva, Juneo F; Martins, Bernardo C; Guimarães, Laís B; Gomez, Marcus Vinícius; Melo, Marília M; Melo, Eliane G

    2014-01-01

    Excessive accumulation of intracellular calcium is the most critical step after spinal cord injury (SCI). Reducing the calcium influx should result in a better recovery from SCI. Calcium channel blockers have been shown a great potential in reducing brain and spinal cord injury. In this study, we first tested the neuroprotective effect of MVIIC on slices of spinal cord subjected to ischemia evaluating cell death and caspase-3 activation. Thereafter, we evaluated the efficacy of MVIIC in ameliorating damage following SCI in rats, for the first time in vivo. The spinal cord slices subjected a pretreatment with MVIIC showed a cell protection with a reduction of dead cells in 24.34% and of caspase-3-specific protease activation. In the in vivo experiment, Wistar rats were subjected to extradural compression of the spinal cord at the T12 vertebral level using a weigh of 70 g/cm, following intralesional treatment with either placebo or MVIIC in different doses (15, 30 and 60 pmol) five minutes after injury. Behavioral testing of hindlimb function was done using the Basso Beattie Bresnahan locomotor rating scale, and revealed significant recovery with 15 pmol (G15) compared to other trauma groups. Also, histological bladder structural revealed significant outcome in G15, with no morphological alterations, and anti-NeuN and TUNEL staining showed that G15 provided neuron preservation and indicated that this group had fewer neuron cell death, similar to sham. These results showed the neuroprotective effects of MVIIC in in vitro and in vivo model of SCI with neuronal integrity, bladder and behavioral improvements. PMID:25120731

  16. Intranasal Administration of Interferon Beta Attenuates Neuronal Apoptosis via the JAK1/STAT3/BCL-2 Pathway in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy

    PubMed Central

    Dixon, Brandon J.; Chen, Di; Zhang, Yang; Flores, Jerry; Malaguit, Jay; Nowrangi, Derek; Zhang, John H.

    2016-01-01

    Neonatal hypoxic-ischemic encephalopathy (HIE) is an injury that often leads to detrimental neurological deficits. Currently, there are no established therapies for HIE and it is critical to develop treatments that provide protection after HIE. The objective of this study was to investigate the ability of interferon beta (IFNβ) to provide neuroprotection and reduce apoptosis after HIE. Postnatal Day 10 rat pups were subjected to unilateral carotid artery ligation followed by 2.5 hr of exposure to hypoxia (8% O2). Intranasal administration of human recombinant IFNβ occurred 2 hr after HIE and infarct volume, body weight, neurobehavioral tests, histology, immunohistochemistry, brain water content, blood–brain barrier permeability, enzyme-linked immunosorbent assay, and Western blot were all used to evaluate various parameters. The results showed that both IFNβ and the Type 1 interferon receptor expression decreases after HIE. Intranasal administration of human recombinant IFNβ was able to be detected in the central nervous system and was able to reduce brain infarction volumes and improve neurological behavior tests 24 hr after HIE. Western blot analysis also revealed that human recombinant IFNβ treatment stimulated Stat3 and Bcl-2 expression leading to a decrease in cleaved caspase-3 expression after HIE. Positive Fluoro-Jade C staining also demonstrated that IFNβ treatment was able to decrease neuronal apoptosis. Furthermore, the beneficial effects of IFNβ treatment were reversed when a Stat3 inhibitor was applied. Also an intraperitoneal administration of human recombinant IFNβ into the systemic compartment was unable to confer the same protective effects as intranasal IFNβ treatment. PMID:27683877

  17. Influenza Virus Detection Following Administration of Live-Attenuated Intranasal Influenza Vaccine in Children With Cystic Fibrosis and Their Healthy Siblings

    PubMed Central

    Boikos, Constantina; Joseph, Lawrence; Martineau, Christine; Papenburg, Jesse; Scheifele, David; Lands, Larry C.; De Serres, Gaston; Chilvers, Mark; Quach, Caroline

    2016-01-01

    Background. We aimed to explore the detection profile of influenza viruses following live-attenuated intranasal influenza vaccination (LAIV) in children aged 2–19 years with and without cystic fibrosis (CF). Methods. Before the 2013–2014 influenza season, flocked nasal swabs were obtained before vaccination and 4 times in the week of follow-up from 76 participants (nCF: 57; nhealthy: 19). Influenza was detected by reverse transcription polymerase chain reaction (RT-PCR) assays. A Bayesian hierarchical logistic regression model was used to estimate the effect of CF status and age on influenza detection. Results. Overall, 69% of the study cohort shed influenza RNA during follow-up. The mean duration of RT-PCR detection was 2.09 days (95% credible interval [CrI]: 1.73–2.48). The odds of influenza RNA detection on day 1 following vaccination decreased with age in years (odds ratio [OR]: 0.82 per year; 95% CrI: 0.70–0.95), and subjects with CF had higher odds of influenza RNA detection on day 1 of follow-up (OR: 5.09; 95% CrI: 1.02–29.9). Conclusion. Despite the small sample size, our results indicate that LAIV vaccine strains are detectable during the week after LAIV, mainly in younger individuals and vaccinees with CF. It remains unclear whether recommendations for avoiding contact with severely immunocompromised patients should differ for these groups. PMID:27747255

  18. Administration of NaHS Attenuates Footshock-Induced Pathologies and Emotional and Cognitive Dysfunction in Triple Transgenic Alzheimer’s Mice

    PubMed Central

    Huang, Hei-Jen; Chen, Shu-Ling; Hsieh-Li, Hsiu Mei

    2015-01-01

    Alzheimer’s disease (AD) is characterized by progressive cognitive decline and neuropsychiatric symptoms. Increasing evidence indicates that environmental risk factors in young adults may accelerate cognitive loss in AD and that Hydrogen Sulfide (H2S) may represent an innovative treatment to slow the progression of AD. Therefore, the aim of this study was to evaluate the effects of NaHS, an H2S donor, in a triple transgenic AD mouse model (3×Tg-AD) under footshock with situational reminders (SRs). Inescapable footshock with SRs induced anxiety and cognitive dysfunction as well as a decrease in the levels of plasma H2S and GSH and an increase in IL-6 levels in 3×Tg-AD mice. Under footshock with SR stimulus, amyloid deposition, tau protein hyperphosphorylation, and microgliosis were highly increased in the stress-responsive brain structures, including the hippocampus and amygdala, of the AD mice. Oxidative stress, inflammatory response, and β-site APP cleaving enzyme 1 (BACE1) levels were also increased, and the level of inactivated glycogen synthase kinase-3β (GSK3β) (pSer9) was decreased in the hippocampi of AD mice subjected to footshock with SRs. Furthermore, the numbers of cholinergic neurons in the medial septum/diagonal band of Broca (MS/DB) and noradrenergic neurons in the locus coeruleus (LC) were also decreased in the 3×Tg-AD mice under footshock with SRs. These biochemical hallmarks and pathological presentations were all alleviated by the semi-acute administration of NaHS in the AD mice. Together, these findings suggest that footshock with SRs induces the impairment of spatial cognition and emotion, which involve pathological changes in the peripheral and central systems, including the hippocampus, MS/DB, LC, and BLA, and that the administration of NaHS may be a candidate strategy to ameliorate the progression of neurodegeneration. PMID:26635562

  19. Keratinocyte growth factor administration attenuates murine pulmonary mycobacterium tuberculosis infection through granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent macrophage activation and phagolysosome fusion.

    PubMed

    Pasula, Rajamouli; Azad, Abul K; Gardner, Jason C; Schlesinger, Larry S; McCormack, Francis X

    2015-03-13

    Augmentation of innate immune defenses is an appealing adjunctive strategy for treatment of pulmonary Mycobacterium tuberculosis infections, especially those caused by drug-resistant strains. The effect of intranasal administration of keratinocyte growth factor (KGF), an epithelial mitogen and differentiation factor, on M. tuberculosis infection in mice was tested in prophylaxis, treatment, and rescue scenarios. Infection of C57BL6 mice with M. tuberculosis resulted in inoculum size-dependent weight loss and mortality. A single dose of KGF given 1 day prior to infection with 10(5) M. tuberculosis bacilli prevented weight loss and enhanced pulmonary mycobacterial clearance (compared with saline-pretreated mice) for up to 28 days. Similar effects were seen when KGF was delivered intranasally every third day for 15 days, but weight loss and bacillary growth resumed when KGF was withdrawn. For mice with a well established M. tuberculosis infection, KGF given every 3 days beginning on day 15 postinoculation was associated with reversal of weight loss and an increase in M. tuberculosis clearance. In in vitro co-culture experiments, M. tuberculosis-infected macrophages exposed to conditioned medium from KGF-treated alveolar type II cell (MLE-15) monolayers exhibited enhanced GM-CSF-dependent killing through mechanisms that included promotion of phagolysosome fusion and induction of nitric oxide. Alveolar macrophages from KGF-treated mice also exhibited enhanced GM-CSF-dependent phagolysosomal fusion. These results provide evidence that administration of KGF promotes M. tuberculosis clearance through GM-CSF-dependent mechanisms and enhances host defense against M. tuberculosis infection.

  20. Repeated dose (28-day) administration of silver nanoparticles of varied size and coating does not significantly alter the indigenous murine gut microbiome.

    PubMed

    Wilding, Laura A; Bassis, Christine M; Walacavage, Kim; Hashway, Sara; Leroueil, Pascale R; Morishita, Masako; Maynard, Andrew D; Philbert, Martin A; Bergin, Ingrid L

    2016-01-01

    Silver nanoparticles (AgNPs) have been used as antimicrobials in a number of applications, including topical wound dressings and coatings for consumer products and biomedical devices. Ingestion is a relevant route of exposure for AgNPs, whether occurring unintentionally via Ag dissolution from consumer products, or intentionally from dietary supplements. AgNP have also been proposed as substitutes for antibiotics in animal feeds. While oral antibiotics are known to have significant effects on gut bacteria, the antimicrobial effects of ingested AgNPs on the indigenous microbiome or on gut pathogens are unknown. In addition, AgNP size and coating have been postulated as significantly influential towards their biochemical properties and the influence of these properties on antimicrobial efficacy is unknown. We evaluated murine gut microbial communities using culture-independent sequencing of 16S rRNA gene fragments following 28 days of repeated oral dosing of well-characterized AgNPs of two different sizes (20 and 110 nm) and coatings (PVP and Citrate). Irrespective of size or coating, oral administration of AgNPs at 10 mg/kg body weight/day did not alter the membership, structure or diversity of the murine gut microbiome. Thus, in contrast to effects of broad-spectrum antibiotics, repeat dosing of AgNP, at doses equivalent to 2000 times the oral reference dose and 100-400 times the effective in vitro anti-microbial concentration, does not affect the indigenous murine gut microbiome.

  1. Single administration of tripeptide α-MSH(11-13) attenuates brain damage by reduced inflammation and apoptosis after experimental traumatic brain injury in mice.

    PubMed

    Schaible, Eva-Verena; Steinsträßer, Arne; Jahn-Eimermacher, Antje; Luh, Clara; Sebastiani, Anne; Kornes, Frida; Pieter, Dana; Schäfer, Michael K; Engelhard, Kristin; Thal, Serge C

    2013-01-01

    Following traumatic brain injury (TBI) neuroinflammatory processes promote neuronal cell loss. Alpha-melanocyte-stimulating hormone (α-MSH) is a neuropeptide with immunomodulatory properties, which may offer neuroprotection. Due to short half-life and pigmentary side-effects of α-MSH, the C-terminal tripeptide α-MSH(11-13) may be an anti-inflammatory alternative. The present study investigated the mRNA concentrations of the precursor hormone proopiomelanocortin (POMC) and of melanocortin receptors 1 and 4 (MC1R/MC4R) in naive mice and 15 min, 6, 12, 24, and 48 h after controlled cortical impact (CCI). Regulation of POMC and MC4R expression did not change after trauma, while MC1R levels increased over time with a 3-fold maximum at 12 h compared to naive brain tissue. The effect of α-MSH(11-13) on secondary lesion volume determined in cresyl violet stained sections (intraperitoneal injection 30 min after insult of 1 mg/kg α-MSH(11-13) or 0.9% NaCl) showed a considerable smaller trauma in α-MSH(11-13) injected mice. The expression of the inflammatory markers TNF-α and IL-1β as well as the total amount of Iba-1 positive cells were not reduced. However, cell branch counting of Iba-1 positive cells revealed a reduced activation of microglia. Furthermore, tripeptide injection reduced neuronal apoptosis analyzed by cleaved caspase-3 and NeuN staining. Based on the results single α-MSH(11-13) administration offers a promising neuroprotective property by modulation of inflammation and prevention of apoptosis after traumatic brain injury.

  2. Previous stress attenuates the susceptibility to Midazolam's disruptive effect on fear memory reconsolidation: influence of pre-reactivation D-cycloserine administration.

    PubMed

    Bustos, Silvia Gabriela; Giachero, Marcelo; Maldonado, Héctor; Molina, Víctor Alejandro

    2010-04-01

    It is well known that, under certain boundary conditions, the retrieval of a stable consolidated memory results into a labile one. During this unstable phase, memory can be vulnerable to interference by a number of pharmacological agents, including benzodiazepines. One of the goals of this study was to evaluate the vulnerability to midazolam (MDZ) after reactivation of recent and remote contextual fear memories in animals that experienced a stressful situation before learning. Animals were subjected to a restraint session and trained in a contextual fear paradigm the following day; consolidated memories were reactivated at different times after learning and different MDZ doses (1.5, 3.0 mg/kg) were administered to rats after reactivation. Our results show that MDZ did not affect memory reconsolidation in older-than-one-day memories of stressed animals, even after the administration of a higher MDZ dose and a longer reactivation session (5 min). In contrast, MDZ was effective in blocking reconsolidation at all memory ages in unstressed animals. In addition, the current research investigated whether activating NMDA sites before reactivation promotes the destabilization of resistant memories such as those of stressed animals. We tested the influence of pre-reactivation D-cycloserine (DCS), a partial NMDA agonist, on MDZ's effect on fear memory reconsolidation in stressed animals. Our findings indicate that DCS before reactivation promotes retrieval-induced lability in resistant memory traces, as MDZ-induced memory impairment in stressed rats became evident with pre-reactivation DCS but not after pre-reactivation sterile isotonic saline.

  3. Control algorithms for dynamic attenuators

    SciTech Connect

    Hsieh, Scott S.; Pelc, Norbert J.

    2014-06-15

    modulation) without increasing peak variance. The 15-element piecewise-linear dynamic attenuator reduces dose by an average of 42%, and the perfect attenuator reduces dose by an average of 50%. Improvements in peak variance are several times larger than improvements in mean variance. Heuristic control eliminates the need for a prescan. For the piecewise-linear attenuator, the cost of heuristic control is an increase in dose of 9%. The proposed iterated WMV minimization produces results that are within a few percent of the true solution. Conclusions: Dynamic attenuators show potential for significant dose reduction. A wide class of dynamic attenuators can be accurately controlled using the described methods.

  4. Mass Administration of Ivermectin for the Elimination of Onchocerciasis Significantly Reduced and Maintained Low the Prevalence of Strongyloides stercoralis in Esmeraldas, Ecuador

    PubMed Central

    Anselmi, Mariella; Buonfrate, Dora; Guevara Espinoza, Angel; Prandi, Rosanna; Marquez, Monica; Gobbo, Maria; Montresor, Antonio; Albonico, Marco; Racines Orbe, Marcia; Bisoffi, Zeno

    2015-01-01

    Objectives To evaluate the effect of ivermectin mass drug administration on strongyloidiasis and other soil transmitted helminthiases. Methods We conducted a retrospective analysis of data collected in Esmeraldas (Ecuador) during surveys conducted in areas where ivermectin was annually administered to the entire population for the control of onchocerciasis. Data from 5 surveys, conducted between 1990 (before the start of the distribution of ivermectin) and 2013 (six years after the interruption of the intervention) were analyzed. The surveys also comprised areas where ivermectin was not distributed because onchocerciasis was not endemic. Different laboratory techniques were used in the different surveys (direct fecal smear, formol-ether concentration, IFAT and IVD ELISA for Strongyloides stercoralis). Results In the areas where ivermectin was distributed the strongyloidiasis prevalence fell from 6.8% in 1990 to zero in 1996 and 1999. In 2013 prevalence in children was zero with stool examination and 1.3% with serology, in adult 0.7% and 2.7%. In areas not covered by ivermectin distribution the prevalence was 23.5% and 16.1% in 1996 and 1999, respectively. In 2013 the prevalence was 0.6% with fecal exam and 9.3% with serology in children and 2.3% and 17.9% in adults. Regarding other soil transmitted helminthiases: in areas where ivermectin was distributed the prevalence of T. trichiura was significantly reduced, while A. lumbricoides and hookworms were seemingly unaffected. Conclusions Periodic mass distribution of ivermectin had a significant impact on the prevalence of strongyloidiasis, less on trichuriasis and apparently no effect on ascariasis and hookworm infections. PMID:26540412

  5. Intranasal administration of a combination of choline chloride, vitamin C, and selenium attenuates the allergic effect in a mouse model of airway disease.

    PubMed

    Bansal, Preeti; Saw, Sanjay; Govindaraj, Dhanapal; Arora, Naveen

    2014-08-01

    Respiratory allergic disease is an inflammatory condition accompanied by oxidative stress. Supplementation of an anti-inflammatory agent with antioxidants may have a therapeutic effect. In this study, the effects of choline chloride in combination with antioxidants were evaluated via the intranasal route in a mouse model of allergic airway disease. Balb/c mice were sensitized on days 0, 7, and 14 and challenged on days 25-30 with cockroach extract (CE) and with a booster challenge on day 38. They were treated with choline chloride (ChCl; 1mg/kg), vitamin C (Vit C; 308.33 mg/kg), and selenium (Se; 1mg/kg) alone or in combination via the intranasal route on days 31, 33, 35, 37, and 39. The mice were sacrificed on day 40 to collect blood, bronchoalveolar lavage fluid, lungs, and spleen. Mice immunized with CE showed a significant increase in airway hyperresponsiveness (AHR), lung inflammation, Th2 cytokines, and the oxidative stress markers intracellular reactive oxygen species and 8-isoprostanes compared to the phosphate-buffered saline control group. A significant decrease was observed in these parameters with all the treatments (p<0.01). The highest decrease was noticed in the ChCl+Vit C+Se-treated group, with AHR decreased to the normal level. This group also showed the highest decrease in airway inflammation (p<0.001), IL-4 and IL-5 (p<0.001), IgE and IgG1 (p<0.001), NF-κB (p<0.001), and 8-isoprostane levels (p<0.001). Glutathione peroxidase activity, which was decreased significantly in CE-immunized mice, was restored to normal levels in this group (p<0.001). IL-10 level was decreased in CE-immunized mice and was restored to normal by combination treatment. The combination treatment induced FOXP3(+) cells in splenocyte culture, responsible for the upregulation of IL-10. In conclusion, the combination of choline chloride, vitamin C, and selenium via the intranasal route reduces AHR, inflammation, and oxidative stress, probably by causing IL-10 production by FOXP

  6. Oral administration of Lactobacillus paracasei L9 attenuates PM2.5-induced enhancement of airway hyperresponsiveness and allergic airway response in murine model of asthma

    PubMed Central

    Zhao, Liang; Hao, Yanling; Guo, Huiyuan; Ren, Fazheng

    2017-01-01

    This study investigated allergy immunotherapy potential of Lactobacillus paracasei L9 to prevent or mitigate the particulate matter 2.5 (PM2.5) enhanced pre-existing asthma in mice. Firstly, we used a mouse model of asthma (a 21-day ovalbumin (OVA) sensitization and challenge model) followed by PM2.5 exposure twice on the same day of the last challenge. PM2.5 was collected from the urban area of Beijing and underwent analysis for metals and polycyclic aromatic hydrocarbon contents. The results showed that PM2.5 exposure enhanced airway hyper-responsiveness (AHR) and lead to a mixed Th2/ IL-17 response in asthmatic mice. Secondly, the PM2.5 exposed asthmatic mice were orally administered with L9 (4×107, 4×109 CFU/mouse, day) from the day of first sensitization to the endpoint, for 20 days, to investigate the potential mitigative effect of L9 on asthma. The results showed that L9 ameliorated PM2.5 exposure enhanced AHR with an approximate 50% decrease in total airway resistance response to methacholine (48 mg/ml). L9 also prevented the exacerbated eosinophil and neutrophil infiltration in bronchoalveolar lavage fluid (BALF), and decreased the serum level of total IgE and OVA-specific IgG1 by 0.44-fold and 0.3-fold, respectively. Additionally, cytokine production showed that L9 significantly decreased T-helper cell type 2 (Th2)–related cytokines (IL-4, -5, -13) and elevated levels of Th1 related IFN-γ in BALF. L9 also reduced the level of IL-17A and increased the level of TGF-β. Taken together, these results indicate that L9 may exert the anti-allergic benefit, possibly through rebalancing Th1/Th2 immune response and modulating IL-17 pro-inflammatory immune response. Thus, L9 is a promising candidate for preventing PM exposure enhanced pre-existing asthma. PMID:28199353

  7. Oral administration of Lactobacillus paracasei L9 attenuates PM2.5-induced enhancement of airway hyperresponsiveness and allergic airway response in murine model of asthma.

    PubMed

    Wang, Xifan; Hui, Yan; Zhao, Liang; Hao, Yanling; Guo, Huiyuan; Ren, Fazheng

    2017-01-01

    This study investigated allergy immunotherapy potential of Lactobacillus paracasei L9 to prevent or mitigate the particulate matter 2.5 (PM2.5) enhanced pre-existing asthma in mice. Firstly, we used a mouse model of asthma (a 21-day ovalbumin (OVA) sensitization and challenge model) followed by PM2.5 exposure twice on the same day of the last challenge. PM2.5 was collected from the urban area of Beijing and underwent analysis for metals and polycyclic aromatic hydrocarbon contents. The results showed that PM2.5 exposure enhanced airway hyper-responsiveness (AHR) and lead to a mixed Th2/ IL-17 response in asthmatic mice. Secondly, the PM2.5 exposed asthmatic mice were orally administered with L9 (4×107, 4×109 CFU/mouse, day) from the day of first sensitization to the endpoint, for 20 days, to investigate the potential mitigative effect of L9 on asthma. The results showed that L9 ameliorated PM2.5 exposure enhanced AHR with an approximate 50% decrease in total airway resistance response to methacholine (48 mg/ml). L9 also prevented the exacerbated eosinophil and neutrophil infiltration in bronchoalveolar lavage fluid (BALF), and decreased the serum level of total IgE and OVA-specific IgG1 by 0.44-fold and 0.3-fold, respectively. Additionally, cytokine production showed that L9 significantly decreased T-helper cell type 2 (Th2)-related cytokines (IL-4, -5, -13) and elevated levels of Th1 related IFN-γ in BALF. L9 also reduced the level of IL-17A and increased the level of TGF-β. Taken together, these results indicate that L9 may exert the anti-allergic benefit, possibly through rebalancing Th1/Th2 immune response and modulating IL-17 pro-inflammatory immune response. Thus, L9 is a promising candidate for preventing PM exposure enhanced pre-existing asthma.

  8. Robust and Balanced Immune Responses to All 4 Dengue Virus Serotypes Following Administration of a Single Dose of a Live Attenuated Tetravalent Dengue Vaccine to Healthy, Flavivirus-Naive Adults

    PubMed Central

    Kirkpatrick, Beth D.; Durbin, Anna P.; Pierce, Kristen K.; Carmolli, Marya P.; Tibery, Cecilia M.; Grier, Palmtama L.; Hynes, Noreen; Diehl, Sean A.; Elwood, Dan; Jarvis, Adrienne P.; Sabundayo, Beulah P.; Lyon, Caroline E.; Larsson, Catherine J.; Jo, Matthew; Lovchik, Janece M.; Luke, Catherine J.; Walsh, Mary C.; Fraser, Ellen A.; Subbarao, Kanta; Whitehead, Steven S.

    2015-01-01

    Background. The 4 serotypes of dengue virus, DENV-1–4, are the leading cause of arboviral disease globally. The ideal dengue vaccine would provide protection against all serotypes after a single dose. Methods. Two randomized, placebo-controlled trials were performed with 168 flavivirus-naive adults to demonstrate the safety and immunogenicity of a live attenuated tetravalent dengue vaccine (TV003), compared with those of a second tetravalent vaccine with an enhanced DENV-2 component (TV005), and to evaluate the benefit of a booster dose at 6 months. Safety data, viremia, and neutralizing antibody titers were evaluated. Results. A single dose of TV005 elicited a tetravalent response in 90% of vaccinees by 3 months after vaccination and a trivalent response in 98%. Compared with TV003, the higher-dose DENV-2 component increased the observed frequency of immunogenicity to DENV-2 in the TV005 trial. Both the first and second doses were well tolerated. Neither vaccine viremia, rash, nor a significant antibody boost were observed following a second dose. Conclusions. A single subcutaneous dose of TV005 dengue vaccine is safe and induces a tetravalent antibody response at an unprecedented frequency among vaccinees. A second dose has limited benefit and appears to be unnecessary. Studies to confirm these findings and assess vaccine efficacy will now move to populations in regions where DENV transmission is endemic. Clinical Trials Registration. NCT01072786 and NCT01436422. PMID:25801652

  9. Ganglioside inserted into PEGylated liposome attenuates anti-PEG immunity.

    PubMed

    Mima, Yu; Abu Lila, Amr S; Shimizu, Taro; Ukawa, Masami; Ando, Hidenori; Kurata, Yasuko; Ishida, Tatsuhiro

    2017-03-28

    Despite the clinical introduction of a vast number of polyethylene glycol (PEG)-conjugated therapeutics, conjugated PEG is also known for an unfortunate inclination toward immunogenicity. Immunogenicity of PEG, manifested by the robust production of anti-PEG IgM, is known to compromise the therapeutic efficacy and/or reduce the tolerance of PEGylated therapeutics. In the present study, we inserted ganglioside into the membrane of PEGylated liposome (PL) to prepare ganglioside-modified PEGylated liposomes (G-PL), and investigated its efficacy in attenuating the anti-PEG IgM response against PL. A single intravenous injection of G-PL significantly attenuated the anti-PEG IgM production, compared with that of naïve PL. In addition, pretreatment with G-PL substantially alleviated the anti-PEG IgM response elicited by a subsequent dose of PL, presumably via inducing B cell tolerance, and as a consequence, this modification abrogated/attenuated the incidence of the rapid clearance of subsequently administrated PL. These results indicate that incorporating gangliosides in PEGylated liposome membrane not only prevents the immunogenicity of PEG but also induces the tolerance of B cells to subsequent doses of the immunogenic PL. Consequently, liposomal membrane modification with ganglioside might represent a promising approach to attenuating the immunogenicity of PEGylated liposomes while preserving their therapeutic efficacy, particularly upon repeated administration.

  10. Therapeutic inhibition of the alternative complement pathway attenuates chronic EAE.

    PubMed

    Hu, Xianzhen; Holers, V Michael; Thurman, Joshua M; Schoeb, Trent R; Ramos, Theresa N; Barnum, Scott R

    2013-07-01

    Previous studies from our laboratory using complement-mutant mice demonstrated that the alternative pathway is the dominant activation pathway responsible for complement-mediated pathology in demyelinating disease. Using a well-characterized inhibitory monoclonal antibody (mAb 1379) directed against mouse factor B, we assessed the therapeutic value of inhibiting the alternative complement pathway in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. Administration of anti-factor B antibody to mice prior to the onset of clinical signs of active EAE had no affect on the onset or acute phase of disease, but significantly attenuated the chronic phase of disease resulting in reduced cellular infiltration, inflammation and demyelination in antibody-treated mice. Attenuation of the chronic phase of disease was long lasting even though antibody administration was terminated shortly after disease onset. Chronic disease was also attenuated in transferred EAE when anti-factor B antibody was administered before or after disease onset. Similar levels of disease attenuation were observed in transferred EAE using MOG-specific encephalitogenic T cells. These studies demonstrate the therapeutic potential for inhibition of factor B in the chronic phase of demyelinating disease, where treatment options are limited.

  11. Therapeutic Inhibition of the Alternative Complement Pathway Attenuates Chronic EAE

    PubMed Central

    Hu, Xianzhen; Holers, V. Michael; Thurman, Joshua M.; Schoeb, Trent R.; Ramos, Theresa N; Barnum, Scott R.

    2013-01-01

    Previous studies from our laboratory using complement-mutant mice demonstrated that the alternative pathway is the dominant activation pathway responsible for complement-mediated pathology in demyelinating disease. Using a well-characterized inhibitory monoclonal antibody (mAb 1379) directed against mouse factor B, we assessed the therapeutic value of inhibiting the alternative complement pathway in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. Administration of anti-factor B antibody to mice prior to the onset of clinical signs of active EAE had no affect on the onset or acute phase of disease, but significantly attenuated the chronic phase of disease resulting in reduced cellular infiltration, inflammation and demyelination in antibody-treated mice. Attenuation of the chronic phase of disease was long lasting even though antibody administration was terminated shortly after disease onset. Chronic disease was also attenuated in transferred EAE when anti-factor B antibody was administered before or after disease onset. Similar levels of disease attenuation were observed in transferred EAE using MOG-specific encephalitogenic T cells. These studies demonstrate the therapeutic potential for inhibition of factor B in the chronic phase of demyelinating disease, where treatment options are limited. PMID:23337717

  12. Short and long access to cocaine self-administration activates tyrosine phosphatase STEP and attenuates GluN expression but differentially regulates GluA expression in the prefrontal cortex

    PubMed Central

    Sun, Wei-Lun; Zelek-Molik, Agnieszka; McGinty, Jacqueline F.

    2013-01-01

    Rationale Dephosphorylation of extracellular signal-regulated kinase (ERK) and cyclic AMP response element binding protein (CREB) in the dorsomedial prefrontal cortex (dmPFC) at the end of short access (ShA) cocaine self-administration is implicated in cocaine-seeking. However, what receptors and phosphatases mediate this effect and whether ERK/CREB and related phospho-proteins in the dmPFC react similarly during early withdrawal from long access (LgA) cocaine self-administration are unknown. Objectives The effects of ShA vs. LgA cocaine self-administration on the phosphorylation of protein phosphatase 2A (PP2A) and striatal-enriched protein tyrosine phosphatase (STEP), as well as GluN and GluA receptor subtype expression in the dmPFC during early withdrawal were compared. Methods Rats self-administered cocaine or received saline during 2-hr or 6-hr daily sessions for 10-11 days. Two hr after the final session, the dmPFC was dissected out and processed for immunoblotting. Results Similar to previous findings after ShA cocaine, phospho-ERK and phospho-CREB in the dmPFC were decreased after LgA cocaine. Cocaine elevated phospho-PP2A (de-activation) and decreased phosphor-STEP (activation) in both ShA and LgA cocaine rats. GluN1, GluN2B and phospho-GluN2B Tyr1472 in the dmPFC were decreased after ShA and LgA cocaine. Further, a significant reduction of GluA2, GluA1 and phospho-GluA1 Ser845 was found only in LgA rats. Conclusions Activation of phospho-STEP may underlie ERK and CREB dephosphorylation in the dmPFC as well as internalization and degradation of GluN complexes during early withdrawal from both ShA and LgA cocaine self-administration whereas differential alteration of AMPA receptor subunits after ShA and LgA cocaine self-administration depends on cocaine intake. PMID:23624776

  13. Intra-Myocardial Injection of Both Growth Factors and Heart Derived Sca-1+/CD31− Cells Attenuates Post-MI LV Remodeling More Than Does Cell Transplantation Alone: Neither Intervention Enhances Functionally Significant Cardiomyocyte Regeneration

    PubMed Central

    Wang, Xiaohong; Li, Qinglu; Hu, Qingsong; Suntharalingam, Piradeep; From, Arthur H. L.; Zhang, Jianyi

    2014-01-01

    Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are two potent cell survival and regenerative factors in response to myocardial injury (MI). We hypothesized that simultaneous delivery of IGF+HGF combined with Sca-1+/CD31− cells would improve the outcome of transplantation therapy in response to the altered hostile microenvironment post MI. One million adenovirus nuclear LacZ-labeled Sca-1+/CD31− cells were injected into the peri-infarction area after left anterior descending coronary artery (LAD) ligation in mice. Recombinant mouse IGF-1+HGF was added to the cell suspension prior to the injection. The left ventricular (LV) function was assessed by echocardiography 4 weeks after the transplantation. The cell engraftment, differentiation and cardiomyocyte regeneration were evaluated by histological analysis. Sca-1+/CD31− cells formed viable grafts and improved LV ejection fraction (EF) (Control, 54.5+/−2.4; MI, 17.6+/−3.1; Cell, 28.2+/−4.2, n = 9, P<0.01). IGF+HGF significantly enhanced the benefits of cell transplantation as evidenced by increased EF (38.8+/−2.2; n = 9, P<0.01) and attenuated adverse structural remodeling. Furthermore, IGF+HGF supplementation increased the cell engraftment rate, promoted the transplanted cell survival, enhanced angiogenesis, and minimally stimulated endogenous cardiomyocyte regeneration in vivo. The in vitro experiments showed that IGF+HGF treatment stimulated Sca-1+/CD31− cell proliferation and inhibited serum free medium induced apoptosis. Supperarray profiling of Sca-1+/CD31− cells revealed that Sca-1+/CD31− cells highly expressed various trophic factor mRNAs and IGF+HGF treatment altered the mRNAs expression patterns of these cells. These data indicate that IGF-1+HGF could serve as an adjuvant to cell transplantation for myocardial repair by stimulating donor cell and endogenous cardiac stem cell survival, regeneration and promoting angiogenesis. PMID:24919180

  14. DC attenuation meter

    DOEpatents

    Hargrove, Douglas L.

    2004-09-14

    A portable, hand-held meter used to measure direct current (DC) attenuation in low impedance electrical signal cables and signal attenuators. A DC voltage is applied to the signal input of the cable and feedback to the control circuit through the signal cable and attenuators. The control circuit adjusts the applied voltage to the cable until the feedback voltage equals the reference voltage. The "units" of applied voltage required at the cable input is the system attenuation value of the cable and attenuators, which makes this meter unique. The meter may be used to calibrate data signal cables, attenuators, and cable-attenuator assemblies.

  15. Administrators: Nursing Home Administrator

    ERIC Educational Resources Information Center

    Kahl, Anne

    1976-01-01

    Responsibilities, skills needed, training needed, earnings, employment outlook, and sources of additional information are outlined for the administrator who holds the top management job in a nursing home. (JT)

  16. Pressure surge attenuator

    DOEpatents

    Christie, Alan M.; Snyder, Kurt I.

    1985-01-01

    A pressure surge attenuation system for pipes having a fluted region opposite crushable metal foam. As adapted for nuclear reactor vessels and heads, crushable metal foam is disposed to attenuate pressure surges.

  17. Dehydroepiandrosterone Attenuates Cocaine-Seeking Behaviour Independently of Corticosterone Fluctuations.

    PubMed

    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.

  18. Nicotine attenuates relapse to methamphetamine-seeking behavior (craving) in rats.

    PubMed

    Hiranita, Takato; Anggadiredja, Kusnandar; Fujisaki, Chie; Watanabe, Shigenori; Yamamoto, Tsuneyuki

    2004-10-01

    This study clarifies the modulating action of the nicotinic cholinergic system on reinstatement of methamphetamine (MAP)-seeking behavior (craving) using an intravenous, self-administration paradigm in rats. After self-administration of MAP for 10 days, replacing MAP with saline solution (MAP withdrawal) gradually decreased lever-pressing responses. On the sixth day of MAP withdrawal, MAP (1.0 mg/kg, i.p.)-priming injection significantly increased lever-pressing responses (reinstatement of MAP-seeking behavior). This MAP-seeking behavior was attenuated by repeated nicotine administration for 5 days during MAP withdrawal, and this attenuating effect was antagonized by the nicotinic antagonist mecamylamine. These results suggest that the appearance of MAP-seeking behavior may be due to inactivation of the nicotinic cholinergic neuron. Furthermore, it is suggested that nicotinic activating agents may be useful in preventing relapse to drug abuse.

  19. Tracer attenuation in groundwater

    NASA Astrophysics Data System (ADS)

    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.

  20. Magnesium nitrate attenuates blood pressure rise in SHR rats.

    PubMed

    Vilskersts, Reinis; Kuka, Janis; Liepinsh, Edgars; Cirule, Helena; Gulbe, Anita; Kalvinsh, Ivars; Dambrova, Maija

    2014-01-01

    The administration of magnesium supplements and nitrates/nitrites decreases arterial blood pressure and attenuates the development of hypertension-induced complications. This study was performed to examine the effects of treatment with magnesium nitrate on the development of hypertension and its complications in spontaneously hypertensive (SHR) rats. Male SHR rats with persistent hypertension at the age of 12-13 weeks were allocated to two groups according to their arterial blood pressure. Rats from the control group received purified water, while the experimental animals from the second group received magnesium nitrate dissolved in purified water at a dose of 50 mg/kg. After four weeks of treatment, blood pressure was measured, the anatomical and functional parameters of the heart were recorded using an ultrasonograph, vascular reactivity was assayed in organ bath experiments and the cardioprotective effects of magnesium nitrate administration was assayed in an ex vivo experimental heart infarction model. Treatment with magnesium nitrate significantly increased the nitrate concentration in the plasma (from 62 ± 8 μmol/l to 111 ± 8 μmol/L), and attenuated the increase in the arterial blood pressure. In the control and magnesium nitrate groups, the blood pressure rose by 21 ± 3 mmHg and 6 ± 4 mmHg, respectively. The administration of magnesium nitrate had no effect on the altered vasoreactivity, heart function or the size of the heart infarction. In conclusion, our results demonstrate that magnesium nitrate effectively attenuates the rise in arterial blood pressure. However, a longer period of administration or earlier onset of treatment might be needed to delay the development of complications due to hypertension.

  1. The UVB-Stimulated Expression of Transglutaminase 1 Is Mediated Predominantly via the NFκB Signaling Pathway: New Evidence of Its Significant Attenuation through the Specific Interruption of the p38/MSK1/NFκBp65 Ser276 Axis

    PubMed Central

    Nakajima, Hiroaki; Yasuda, Michitaka; Imokawa, Genji

    2015-01-01

    The influence of ultraviolet B (UVB) radiation on transglutaminase 1 (TGase 1), a major factor that regulates skin keratinization, has not been sufficiently characterized especially at the gene or protein level. Thus, we determined whether UVB affects the expression of TGase 1 in human keratinocytes and clarified the intracellular stress signaling mechanism(s) involved. Exposure of human keratinocytes to UVB significantly up-regulated the expression of TGase 1 at the gene and protein levels. Treatment with inhibitors of p38, MEK, JNK or NFκB significantly abolished the UVB-stimulated protein expression of TGase 1. Treatment with astaxanthin immediately after UVB irradiation did not attenuate the increased phosphorylation of Ser536/Ser468NFκBp65, c-Jun, ATK-2 and CK2, and did not abrogate the increased or diminished protein levels of c-Jun/c-Fos or I-κBα, respectively. However, the same treatment with astaxanthin significantly abolished the UVB-stimulated expression of TGase 1 protein, which was accompanied by the attenuated phosphorylation of Thr565/Ser376/Ser360MSK1, Ser276NFκBp65 and Ser133CREB. The MSK1 inhibitor H89 significantly down-regulated the increased protein expression of TGase 1 in UVB-exposed human keratinocytes, which was accompanied by an abrogating effect on the increased phosphorylation of Ser276NFκBp65 and Ser133CREB but not Thr565/Ser376/Ser360MSK1. Transfection of human keratinocytes with MSK1 siRNA suppressed the UVB-stimulated protein expression of TGase 1. These findings suggest that the UVB-stimulated expression of TGase 1 is mediated predominantly via the NFκB pathway and can be attenuated through a specific interruption of the p38/MSK1/NFκBp65Ser276 axis. PMID:26305102

  2. No significant differences in the breadth of the foot-and-mouth disease serotype A vaccine induced antibody responses in cattle, using different adjuvants, mixed antigens and different routes of administration.

    PubMed

    Tekleghiorghis, Tesfaalem; Weerdmeester, Klaas; van Hemert-Kluitenberg, Froukje; Moormann, Rob J M; Dekker, Aldo

    2014-09-15

    Inactivated whole virus foot-and-mouth disease (FMD) vaccines are used worldwide for protection against FMD, but not all vaccines induce protection against all genetic variants of the same FMD virus serotype. The aim of this study is to investigate whether the "breadth" of the antibody response against different strains of the same FMD virus serotype in cattle could be improved by using a different adjuvant, a mix of antigens and/or different routes of administration. To this end, six groups of five cattle were vaccinated with different FMD virus serotype A strain vaccines formulated with Montanide ISA 206 VG adjuvant. Antibody responses for homologous and heterologous cross-reactivity against a panel of 10 different FMD virus serotype A strains were tested by a liquid-phase blocking ELISA. Results of cattle vaccinated with ISA 206 VG adjuvanted vaccine were compared with results obtained in a previous study using aluminium hydroxide-saponin adjuvant. No significant effect of adjuvant on the breadth of the antibody response was observed, neither for mixing of antigens nor for the route of administration (subcutaneous vs. intradermal). Comparison of antigen payload, however, increased both homologous and heterologous titres; a 10-fold higher antigen dose resulted in approximately four times higher titres against all tested strains. Our study shows that breadth of the antibody response depends mainly on the vaccine strain; we therefore propose that, for vaccine preparation, only FMD virus strains are selected that, among other important characteristics, will induce a wide antibody response to different field strains.

  3. Variable laser attenuator

    DOEpatents

    Foltyn, Stephen R.

    1988-01-01

    The disclosure relates to low loss, high power variable attenuators comprng one or more transmissive and/or reflective multilayer dielectric filters. The attenuator is particularly suitable to use with unpolarized lasers such as excimer lasers. Beam attenuation is a function of beam polarization and the angle of incidence between the beam and the filter and is controlled by adjusting the angle of incidence the beam makes to the filter or filters. Filters are selected in accordance with beam wavelength.

  4. Variable laser attenuator

    DOEpatents

    Foltyn, S.R.

    1987-05-29

    The disclosure relates to low loss, high power variable attenuators comprising one or more transmissive and/or reflective multilayer dielectric filters. The attenuator is particularly suitable to use with unpolarized lasers such as excimer lasers. Beam attenuation is a function of beam polarization and the angle of incidence between the beam and the filter and is controlled by adjusting the angle of incidence the beam makes to the filter or filters. Filters are selected in accordance with beam wavelength. 9 figs.

  5. Attenuation of tumor necrosis factor-induced endothelial cell cytotoxicity and neutrophil chemiluminescence

    SciTech Connect

    Zheng, H.; Crowley, J.J.; Chan, J.C.; Hoffmann, H.; Hatherill, J.R.; Ishizaka, A.; Raffin, T.A. )

    1990-11-01

    Our laboratory has previously shown that the administration of tumor necrosis factor (TNF), a cytokine produced by activated mononuclear cells, to guinea pigs produces a syndrome similar to gram-negative sepsis or ARDS. Pentoxifylline (PTX), a methylxanthine, protects against TNF-induced and sepsis-induced acute lung injury in vivo. We now report on in vitro cellular studies of PMN-mediated cellular injury and its attenuation. We studied TNF-induced bovine pulmonary artery endothelial cell (EC) cytotoxicity both with and without PMN. A 51Cr release assay was used to measure EC damage. Further, we investigated PMN function in response to TNF by measuring chemiluminescence. Agents that attenuate EC damage and PMN activation were evaluated in the above assays. Results revealed that TNF causes EC injury (p less than 0.05) and PMN increase TNF-induced EC injury. Furthermore, PTX, aminophylline (AMPH), caffeine, and forskolin attenuate TNF-induced EC cytotoxicity only in the presence of PMN (p less than 0.05). Of interest, dibutyryl cAMP (DBcAMP) protects EC from TNF-induced injury both with and without PMN. Agents that may increase cAMP levels in PMN (PTX, DBcAMP, forskolin, isobutyl methylxanthine, and terbutaline) significantly attenuate TNF-induced PMN chemiluminescence (p less than 0.05). We conclude that TNF causes EC damage and PMN increase this damage. Furthermore, PTX, AMPH, caffeine, and forskolin can attenuate TNF-induced EC injury in the presence of PMN, whereas DBcAMP attenuates TNF-induced EC injury with and without PMN. In addition, agents that may increase intracellular cAMP levels in PMN can attenuate TNF-induced PMN chemiluminescence. Thus, these agents likely attenuate TNF-induced PMN-mediated EC injury through their inhibitory effects on PMN.

  6. Combined Administration of Levetiracetam and Valproic Acid Attenuates Age Related Hyperactivity of CA3 Place Cells, Reduces Place Field Area, and Increases Spatial Information Content in Aged Rat Hippocampus

    PubMed Central

    Robitsek, RJ; Ratner, MH; Stewart, TM; Eichenbaum, H; Farb, DH

    2015-01-01

    Learning and memory deficits associated with age-related mild cognitive impairment have long been attributed to impaired processing within the hippocampus. Hyperactivity within the hippocampal CA3 region that is associated with aging is mediated in part by a loss of inhibitory interneurons and thought to underlie impaired performance in spatial memory tasks, including the abnormal tendency in aged animals to pattern complete spatial representations. Here, we asked whether the spatial firing patterns of simultaneously recorded CA3 and CA1 neurons in young and aged rats could be manipulated pharmacologically to selectively reduce CA3 hyperactivity and thus, according to hypothesis, the associated abnormality in spatial representations. We used chronically implanted high-density tetrodes to record the spatial firing properties of CA3 and CA1 units during animal exploration for food in familiar and novel environments. Aged CA3 place cells have higher firing rates, larger place fields, less spatial information content, and respond less to a change from a familiar to a novel environment than young CA3 cells. We also find that the combination of levetiracetam (LEV) + valproic acid (VPA), previously shown to act as a cognitive enhancer in tests of spatial memory, attenuate CA3 place cell firing rates, reduce place field area, and increase spatial information content in aged but not young adult rats. This is consistent with drug enhancing the specificity of neuronal firing with respect to spatial location. Contrary to expectation, however, LEV + VPA reduces place cell discrimination between novel and familiar environments, i.e., spatial correlations increase, independent of age even though drug enhances performance in cognitive tasks. The results demonstrate that spatial information content, or the number of bits of information encoded per action potential, may be the key correlate for enhancement of spatial memory by LEV + VPA. PMID:25941121

  7. Chronic administration of grape-seed polyphenols attenuates the development of hypertension and improves other cardiometabolic risk factors associated with the metabolic syndrome in cafeteria diet-fed rats.

    PubMed

    Pons, Zara; Margalef, Maria; Bravo, Francisca I; Arola-Arnal, Anna; Muguerza, Begoña

    2017-01-01

    The effects of grape-seed polyphenols against the development of hypertension and other cardiometabolic conditions associated with the metabolic syndrome (MetS) were studied in rats fed a high-fat, high-carbohydrate diet, known as the cafeteria (CAF) diet. Two groups of Wistar rats were fed standard (STD) or CAF diets for 12 weeks. The CAF diet-fed rats were administered different doses of a low-molecular-weight grape-seed polyphenol extract (LM-GSPE) (25, 100 and 200 mg/kg per d) or vehicle daily, and the STD diet-fed rats were administered LM-GSPE (100 mg/kg per d) or vehicle using ten animals per group. Body weight (BW), waist perimeter (WP) and systolic and diastolic blood pressures (BP) by the tail-cuff method were recorded weekly. The animals were housed in metabolic chambers every 2 weeks to estimate daily food and liquid intakes and to collect faeces and urine samples. The plasma lipid profile was analysed at time 0 and on the 4th, 7th, 10th and 12th weeks of the experiment. Moreover, plasma leptin was measured at the end of the experiment. Results demonstrated that LM-GSPE, when administered with the CAF diet, attenuated the increase in BP, BW, WP and improved lipid metabolism in these animals. However, although the 25- and 100-mg/kg per d doses were sufficient to produce beneficial effects on BP and lipid metabolism, a 200-mg/kg per d dose was necessary to have an effect on BW and WP. The present findings suggest that LM-GSPE is a good candidate for a BP-lowering agent that can also ameliorate other conditions associated with the MetS.

  8. Combined administration of levetiracetam and valproic acid attenuates age-related hyperactivity of CA3 place cells, reduces place field area, and increases spatial information content in aged rat hippocampus.

    PubMed

    Robitsek, Jonathan; Ratner, Marcia H; Stewart, Tara; Eichenbaum, Howard; Farb, David H

    2015-12-01

    Learning and memory deficits associated with age-related mild cognitive impairment have long been attributed to impaired processing within the hippocampus. Hyperactivity within the hippocampal CA3 region that is associated with aging is mediated in part by a loss of functional inhibitory interneurons and thought to underlie impaired performance in spatial memory tasks, including the abnormal tendency in aged animals to pattern complete spatial representations. Here, we asked whether the spatial firing patterns of simultaneously recorded CA3 and CA1 neurons in young and aged rats could be manipulated pharmacologically to selectively reduce CA3 hyperactivity and thus, according to hypothesis, the associated abnormality in spatial representations. We used chronically implanted high-density tetrodes to record the spatial firing properties of CA3 and CA1 units during animal exploration for food in familiar and novel environments. Aged CA3 place cells have higher firing rates, larger place fields, less spatial information content, and respond less to a change from a familiar to a novel environment than young CA3 cells. We also find that the combination of levetiracetam (LEV) + valproic acid (VPA), previously shown to act as a cognitive enhancer in tests of spatial memory, attenuate CA3 place cell firing rates, reduce place field area, and increase spatial information content in aged but not young adult rats. This is consistent with drug enhancing the specificity of neuronal firing with respect to spatial location. Contrary to expectation, however, LEV + VPA reduces place cell discrimination between novel and familiar environments, i.e., spatial correlations increase, independent of age even though drug enhances performance in cognitive tasks. The results demonstrate that spatial information content, or the number of bits of information encoded per action potential, may be the key correlate for enhancement of spatial memory by LEV + VPA.

  9. Stormwater Attenuation by Green Roofs

    NASA Astrophysics Data System (ADS)

    Sims, A.; O'Carroll, D. M.; Robinson, C. E.; Smart, C. C.

    2014-12-01

    Innovative municipal stormwater management technologies are urgently required in urban centers. Inadequate stormwater management can lead to excessive flooding, channel erosion, decreased stream baseflows, and degraded water quality. A major source of urban stormwater is unused roof space. Green roofs can be used as a stormwater management tool to reduce roof generated stormwater and generally improve the quality of runoff. With recent legislation in some North American cities, including Toronto, requiring the installation of green roofs on large buildings, research on the effectiveness of green roofs for stormwater management is important. This study aims to assess the hydrologic response of an extensive sedum green roof in London, Ontario, with emphasis on the response to large precipitation events that stress municipal stormwater infrastructure. A green roof rapidly reaches field capacity during large storm events and can show significantly different behavior before and after field capacity. At field capacity a green roof has no capillary storage left for retention of stormwater, but may still be an effective tool to attenuate peak runoff rates by transport through the green roof substrate. The attenuation of green roofs after field capacity is linked to gravity storage, where gravity storage is the water that is temporarily stored and can drain freely over time after field capacity has been established. Stormwater attenuation of a modular experimental green roof is determined from water balance calculations at 1-minute intervals. Data is used to evaluate green roof attenuation and the impact of field capacity on peak flow rates and gravity storage. In addition, a numerical model is used to simulate event based stormwater attenuation. This model is based off of the Richards equation and supporting theory of multiphase flow through porous media.

  10. RADIO FREQUENCY ATTENUATOR

    DOEpatents

    Giordano, S.

    1963-11-12

    A high peak power level r-f attenuator that is readily and easily insertable along a coaxial cable having an inner conductor and an outer annular conductor without breaking the ends thereof is presented. Spaced first and second flares in the outer conductor face each other with a slidable cylindrical outer conductor portion therebetween. Dielectric means, such as water, contact the cable between the flares to attenuate the radio-frequency energy received thereby. The cylindrical outer conductor portion is slidable to adjust the voltage standing wave ratio to a low level, and one of the flares is slidable to adjust the attenuation level. An integral dielectric container is also provided. (AFC)

  11. Landing gear noise attenuation

    NASA Technical Reports Server (NTRS)

    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.

  12. Curcumin attenuates elastase- and cigarette smoke-induced pulmonary emphysema in mice.

    PubMed

    Suzuki, Masaru; Betsuyaku, Tomoko; Ito, Yoko; Nagai, Katsura; Odajima, Nao; Moriyama, Chinatsu; Nasuhara, Yasuyuki; Nishimura, Masaharu

    2009-04-01

    Curcumin, a yellow pigment obtained from turmeric (Curcumina longa), is a dietary polyphenol that has been reported to possess anti-inflammatory and antioxidant properties. The effect of curcumin against the development of pulmonary emphysema in animal models is unknown. The aim of this study was to determine whether curcumin is able to attenuate the development of pulmonary emphysema in mice. Nine-week-old male C57BL/6J mice were treated with intratracheal porcine pancreatic elastase (PPE) or exposed to mainstream cigarette smoke (CS) (60 min/day for 10 consecutive days or 5 days/wk for 12 wk) to induce pulmonary inflammation and emphysema. Curcumin (100 mg/kg) or vehicle was administrated daily by oral gavage 1 h and 24 h before intratracheal PPE treatment and daily thereafter throughout a 21-day period in PPE-exposed mice and 1 h before each CS exposure in CS-exposed mice. As a result, curcumin treatment significantly inhibited PPE-induced increase of neutrophils in bronchoalveolar lavage fluid at 6 h and on day 1 after PPE administration, with an increase in antioxidant gene expression at 6 h and significantly attenuated PPE-induced air space enlargement on day 21. It was also found that curcumin treatment significantly inhibited CS-induced increase of neutrophils and macrophages in bronchoalveolar lavage fluid after 10 consecutive days of CS exposure and significantly attenuated CS-induced air space enlargement after 12 wk of CS exposure. In conclusion, oral curcumin administration attenuated PPE- and CS-induced pulmonary inflammation and emphysema in mice.

  13. Pharmacological administration of granulocyte/macrophage-colony-stimulating factor is of significant importance for the induction of a strong humoral and cellular response in patients immunized with recombinant carcinoembryonic antigen.

    PubMed

    Samanci, A; Yi, Q; Fagerberg, J; Strigård, K; Smith, G; Rudén, U; Wahren, B; Mellstedt, H

    1998-11-01

    Eighteen colorectal carcinoma patients without macroscopic disease after surgery were immunized using recombinant (r) human (h) carcinoembryonic antigen (CEA) with (n=9) or without (n=9) the addition of soluble granulocyte/macrophage-colony-stimulating factor (GM-CSF). The dose of rhCEA per immunization was 100 microg (n=6), 316 microg (n=6) or 1000 microg (n=6). rhCEA was given s.c. on day 1 and 80 microg/day of GM-CSF s.c. on days 1-4. The schedule was repeated six times during a period of 9 months. All patients in the GM-CSF group developed a strong rhCEA-dose-dependent IgG antibody response while only one-third of the non-GM-CSF patients mounted a weak antibody response. All patients (9/9) in the GM-CSF group developed a strong rhCEA-specific proliferative T cell response as well as type I T cells (interferon gamma secretion). In 45% of the patients also a weak type II T cell response (interleukin-4 secretion) was evoked. Both MHC-class-I- and -II restricted rhCEA-specific T cells were noted. A specific cellular response (proliferation and/or cytokine secretion) against native hCEA could be found in 8/9 patients in the GM-CSF group, although at a significantly lower level than against rhCEA. In the non-GM-CSF group a weak rhCEA-specific T cell response was induced. Three patients had a proliferative response, 4 patients type I T cells and 6 patients type II T cells. No signs of autoimmune reactions were noted. Local pharmacological administration of GM-CSF seemed to be a prerequisite for the induction of a strong immunity against baculovirus-produced hCEA protein. However, the cellular response against native CEA was of a significantly lower magnitude.

  14. Attenuator And Conditioner

    DOEpatents

    Anderson, Gene R.; Armendariz, Marcelino G.; Carson, Richard F.; Bryan, Robert P.; Duckett, III, Edwin B.; Kemme, Shanalyn Adair; McCormick, Frederick B.; Peterson, David W.

    2006-04-04

    An apparatus and method of attenuating and/or conditioning optical energy for an optical transmitter, receiver or transceiver module is disclosed. An apparatus for attenuating the optical output of an optoelectronic connector including: a mounting surface; an array of optoelectronic devices having at least a first end; an array of optical elements having at least a first end; the first end of the array of optical elements optically aligned with the first end of the array of optoelectronic devices; an optical path extending from the first end of the array of optoelectronic devices and ending at a second end of the array of optical elements; and an attenuator in the optical path for attenuating the optical energy emitted from the array of optoelectronic devices. Alternatively, a conditioner may be adapted in the optical path for conditioning the optical energy emitted from the array of optoelectronic devices.

  15. Administrative Synergy

    ERIC Educational Resources Information Center

    Hewitt, Kimberly Kappler; Weckstein, Daniel K.

    2012-01-01

    One of the biggest obstacles to overcome in creating and sustaining an administrative professional learning community (PLC) is time. Administrators are constantly deluged by the tyranny of the urgent. It is a Herculean task to carve out time for PLCs, but it is imperative to do so. In this article, the authors describe how an administrative PLC…

  16. Broncho-Vaxom Attenuates Allergic Airway Inflammation by Restoring GSK3β-Related T Regulatory Cell Insufficiency

    PubMed Central

    Zhong, Hua; Yu, Dehong; Zeng, Xianping; Deng, Mengxia; Sun, Yueqi; Wen, Weiping; Li, Huabin

    2014-01-01

    Background Oral administration of bacterial extracts (eg, Broncho-Vaxom (BV)) has been proposed to attenuate asthma through modulating Treg cells. However, the underlying mechanism has not been fully characterized. This study sought to assess the effects of oral administration of BV on GSK-3β expression and Treg cells in ovalbumin (OVA)-induced asthmatic mice models. Method Asthmatic mice models were established with OVA challenge and treated with oral administration of BV. Next, infiltration of inflammatory cells including eosinophil and neutrophils, mucous metaplasia, levels of Th1/Th2/Treg-typed cytokines and expression of GSK3β and Foxp3 were examined in asthmatic mice models by histological analysis, Bio-Plex and western blot, respectively. Moreover, the frequencies of Treg cells were evaluated in cultured splenocytes by flow cytometry in the presence of BV or GSK3β siRNA interference. Results We found significant decrease of infiltrated inflammatory cells in bronchoalveolar lavage fluid (BALF) in asthmatic mice models after oral administration of BV. Oral administration of BV was shown to significantly suppress mucus metaplasia, Th2-typed cytokine levels and GSK3β expression while increasing Foxp3 production in asthmatic mice models. Moreover, BV significantly enhanced GSK3β-related expansion of Treg cells in cultured spleen cells in vitro. Conclusion Our findings provide evidence that oral administration of BV is capable of attenuating airway inflammation in asthmatic mice models, which may be associated with GSK3β-related expansion of Treg cells. PMID:24667347

  17. Neuroprotective effects of creatine administration against NMDA and malonate toxicity.

    PubMed

    Malcon, C; Kaddurah-Daouk, R; Beal, M F

    2000-03-31

    We examined whether creatine administration could exert neuroprotective effects against excitotoxicity mediated by N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainic acid. Oral administration of 1% creatine significantly attenuated striatal excitotoxic lesions produced by NMDA, but had no effect on lesions produced by AMPA or kainic acid. Both creatine and nicotinamide can exert significant protective effects against malonate-induced striatal lesions. We, therefore, examined whether nicotinamide could exert additive neuroprotective effects with creatine against malonate-induced lesions. Nicotinamide with creatine produced significantly better neuroprotection than creatine alone against malonate-induced lesions. Creatine can, therefore, produce significant neuroprotective effects against NMDA mediated excitotoxic lesions in vivo and the combination of nicotinamide with creatine exerts additive neuroprotective effects.

  18. Aggregated single-walled carbon nanotubes attenuate the behavioural and neurochemical effects of methamphetamine in mice

    NASA Astrophysics Data System (ADS)

    Xue, Xue; Yang, Jing-Yu; He, Yi; Wang, Li-Rong; Liu, Ping; Yu, Li-Sha; Bi, Guo-Hua; Zhu, Ming-Ming; Liu, Yue-Yang; Xiang, Rong-Wu; Yang, Xiao-Ting; Fan, Xin-Yu; Wang, Xiao-Min; Qi, Jia; Zhang, Hong-Jie; Wei, Tuo; Cui, Wei; Ge, Guang-Lu; Xi, Zheng-Xiong; Wu, Chun-Fu; Liang, Xing-Jie

    2016-07-01

    Methamphetamine (METH) abuse is a serious social and health problem worldwide. At present, there are no effective medications to treat METH addiction. Here, we report that aggregated single-walled carbon nanotubes (aSWNTs) significantly inhibited METH self-administration, METH-induced conditioned place preference and METH- or cue-induced relapse to drug-seeking behaviour in mice. The use of aSWNTs alone did not significantly alter the mesolimbic dopamine system, whereas pretreatment with aSWNTs attenuated METH-induced increases in extracellular dopamine in the ventral striatum. Electrochemical assays suggest that aSWNTs facilitated dopamine oxidation. In addition, aSWNTs attenuated METH-induced increases in tyrosine hydroxylase or synaptic protein expression. These findings suggest that aSWNTs may have therapeutic effects for treatment of METH addiction by oxidation of METH-enhanced extracellular dopamine in the striatum.

  19. Seismic attenuation in Florida

    SciTech Connect

    Bellini, J.J.; Bartolini, T.J.; Lord, K.M.; Smith, D.L. . Dept. of Geology)

    1993-03-01

    Seismic signals recorded by the expanded distribution of earthquake seismograph stations throughout Florida and data from a comprehensive review of record archives from stations GAI contribute to an initial seismic attenuation model for the Florida Plateau. Based on calculations of surface particle velocity, a pattern of attenuation exists that appears to deviate from that established for the remainder of the southeastern US. Most values suggest greater seismic attenuation within the Florida Plateau. However, a separate pattern may exist for those signals arising from the Gulf of Mexico. These results have important implications for seismic hazard assessments in Florida and may be indicative of the unique lithospheric identity of the Florida basement as an exotic terrane.

  20. Radiofrequency attenuator and method

    DOEpatents

    Warner, Benjamin P.; McCleskey, T. Mark; Burrell, Anthony K.; Agrawal, Anoop; Hall, Simon B.

    2009-11-10

    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.3 C.sup.-). Radicals or radical cations may be added to or electrochemically generated in the molten salt to enhance the RF attenuation.

  1. Radiofrequency attenuator and method

    DOEpatents

    Warner, Benjamin P.; McCleskey, T. Mark; Burrell, Anthony K.; Agrawal, Anoop; Hall, Simon B.

    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.

  2. Administrative Ecology

    ERIC Educational Resources Information Center

    McGarity, Augustus C., III; Maulding, Wanda

    2007-01-01

    This article discusses how all four facets of administrative ecology help dispel the claims about the "impossibility" of the superintendency. These are personal ecology, professional ecology, organizational ecology, and community ecology. Using today's superintendency as an administrative platform, current literature describes a preponderance of…

  3. Tritium Attenuation by Distillation

    SciTech Connect

    Wittman, N.E.

    2001-07-31

    The objective of this study was to determine how a 100 Area distillation system could be used to reduce to a satisfactory low value the tritium content of the dilute moderator produced in the 100 Area stills, and whether such a tritium attenuator would have sufficient capacity to process all this material before it is sent to the 400 Area for reprocessing.

  4. Pomegranate juice intake attenuates the increase in oxidative stress induced by intravenous iron during hemodialysis.

    PubMed

    Shema-Didi, Lilach; Kristal, Batya; Ore, Liora; Shapiro, Galina; Geron, Ronit; Sela, Shifra

    2013-06-01

    The hemodialysis (HD) procedure induces oxidative stress (OS), which is further aggravated by intravenous (IV) iron administration, aimed at correcting anemia of patients with HD. We have recently shown that 1 year of pomegranate juice (PJ) intake attenuated OS and inflammation in patients with HD. In the current study, we hypothesized that a single dose of PJ can attenuate the enhanced OS and inflammation induced by both the dialysis procedure and IV iron administration during HD session. Twenty-seven patients with HD were randomized to receive PJ or placebo during 1 dialysis session with IV iron. Blood samples were drawn before and after the session to asses OS biomarkers such as advanced oxidation protein products and myeloperoxidase (MPO), whereas polymorphonuclear leukocyte (PMNL) counts served as an indirect measure of inflammation. At the end of the dialysis session, an increase in advanced oxidation protein products and MPO levels as well as a decrease in PMNLs counts were observed in the placebo group, whereas no significant changes occurred in the PJ group. The postdialysis increase in MPO levels in the placebo group is a direct result of PMNL degranulation, associated with postdialysis decrease in PMNL counts. Degranulation of PMNLs leads to the release of other cell moieties, such as inflammatory mediators and proteases that enhance inflammation. We conclude that PJ intake attenuated the increase in systemic OS and inflammation induced by IV iron administration during the dialysis session. These beneficial effects illuminate the previously observed attenuation in OS and inflammation in patients with HD on prolonged PJ intake.

  5. Lophirones B and C Attenuate Acetaminophen-Induced Liver Damage in Mice: Studies on Hepatic, Oxidative Stress and Inflammatory Biomarkers.

    PubMed

    Ajiboye, Taofeek O

    2016-10-01

    Lophirones B and C are chalcone dimers with proven chemopreventive activity. This study evaluates the hepatoprotective effect lophirones B and C in acetaminophen-induced hepatic damage in mice using biomarkers of hepatocellular indices, oxidative stress, proinflammatory factors and lipid peroxidation. Oral administrations of lophirones B and C significantly (p < 0.05) attenuated acetaminophen-mediated alterations in serum alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, albumin and total bilirubin. Similarly, acetaminophen-mediated decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose 6- phosphate dehydrogenase were significantly attenuated in the liver of mice. Increased levels of conjugated dienes, lipid hydroperoxides, malondialdehyde, protein carbonyl and fragmented DNA were significantly lowered by lophirones B and C. Levels of tumour necrosis factor-α, interleukin-6 and 8 were significantly lowered in serum of acetaminophen treated mice by the chalcone dimers. Overall, results of this study show that lophirones B and C halted acetaminophen-mediated hepatotoxicity.

  6. Curcumin attenuates oxidative stress following downhill running-induced muscle damage.

    PubMed

    Kawanishi, Noriaki; Kato, Kouki; Takahashi, Masaki; Mizokami, Tsubasa; Otsuka, Yoshihiko; Imaizumi, Atsushi; Shiva, Daisuke; Yano, Hiromi; Suzuki, Katsuhiko

    2013-11-22

    Downhill running causes muscle damage, and induces oxidative stress and inflammatory reaction. Recently, it is shown that curcumin possesses anti-oxidant and anti-inflammatory potentials. Interestingly, curcumin reduces inflammatory cytokine concentrations in skeletal muscle after downhill running of mice. However, it is not known whether curcumin affects oxidative stress after downhill running-induced muscle damage. Therefore, the purpose of this study was to investigate the effects of curcumin on oxidative stress following downhill running induced-muscle damage. We also investigated whether curcumin affects macrophage infiltration via chemokines such as MCP-1 and CXCL14. Male C57BL/6 mice were divided into four groups; rest, rest plus curcumin, downhill running, or downhill running plus curcumin. Downhill running mice ran at 22 m/min, -15% grade on the treadmill for 150 min. Curcumin (3mg) was administered in oral administration immediately after downhill running. Hydrogen peroxide concentration and NADPH-oxidase mRNA expression in the downhill running mice were significantly higher than those in the rest mice, but these variables were significantly attenuated by curcumin administration in downhill running mice. In addition, mRNA expression levels of MCP-1, CXCL14 and F4/80 reflecting presence of macrophages in the downhill running mice were significantly higher than those in the rest mice. However, MCP-1 and F4/80 mRNA expression levels were significantly attenuated by curcumin administration in downhill running mice. Curcumin may attenuate oxidative stress following downhill running-induced muscle damage.

  7. A Novel Strategy for Attenuating Opioid Withdrawal in Neonates

    PubMed Central

    Santoro, Giovanni C; Shukla, Samarth; Patel, Krishna; Kaczmarzyk, Jakub; Agorastos, Stergiani; Scherrer, Sandra; Choi, Yoon Young; Veith, Christina; Carrion, Joseph; Silverman, Rebecca; Mullin, Danielle; Ahmed, Mohamed; Schiffer, Wynne K; Brodie, Jonathan D; Dewey, Stephen L

    2016-01-01

    The rate of Neonatal Abstinence Syndrome (NAS) has drastically increased over the past decade. The average hospital expense per NAS patient has tripled, while the number of babies born to opioid-dependent mothers has increased to 5 in 1000 births. Current treatment options are limited to opioid replacement and tapering. Consequently, we examined the efficacy of prenatal, low-dose and short-term vigabatrin (γ-vinyl GABA, GVG) exposure for attenuating these symptoms as well as the metabolic changes observed in the brains of these animals upon reaching adolescence. Pregnant Sprague-Dawley rats were treated in one of four ways: 1) saline; 2) morphine alone; 3) morphine+GVG at 25 mg/kg; 4) morphine+GVG at 50 mg/kg. Morphine was administered throughout gestation, while GVG administration occurred only during the last 5 days of gestation. On post-natal day 1, naloxone-induced withdrawal behaviours were recorded in order to obtain a gross behaviour score. Approximately 28 days following birth, 18FDG microPET scans were obtained on these same animals (Groups 1, 2, and 4). Morphine-treated neonates demonstrated significantly higher withdrawal scores than saline controls. However, GVG at 50 but not 25 mg/kg/day significantly attenuated them. Upon reaching adolescence, morphine treated animals showed regionally specific changes in 18FDG uptake. Again, prenatal GVG exposure blocked them. These data demonstrate that low-dose, short-term prenatal GVG administration blocks naloxone-induced withdrawal in neonates. Taken together, these preliminary findings suggest that GVG may provide an alternative and long-lasting pharmacologic approach for the management of neonatal and adolescent symptoms associated with NAS. PMID:28078167

  8. Hepatocyte growth factor attenuates pancreatic damage in caerulein-induced pancreatitis in rats.

    PubMed

    Warzecha, Z; Dembiński, A; Konturek, P C; Ceranowicz, P; Konturek, S J; Tomaszewska, R; Schuppan, D; Stachura, J; Nakamura, T

    2001-10-26

    Hepatocyte growth factor (HGF) overexpression was reported in experimental and clinical acute pancreatitis. These observations prompted us to determine the effect of HGF administration on the development of caerulein-induced pancreatitis in rats. Acute pancreatitis was induced by s.c. infusion of caerulein (10 microg/kg/h) for 5 h. HGF was administrated twice (30 min before caerulein or saline infusion and 3 h later) at the doses: 0.4, 2, 10 or 50 microg/kg s.c. Immediately after cessation of caerulein or saline infusion, the pancreatic blood flow, plasma amylase and lipase activity, plasma cytokines concentration, cell proliferation, and morphological signs of pancreatitis were examined. Caerulein administration induced acute edematous pancreatitis manifested by 41% decrease in DNA synthesis, 53% inhibition of pancreatic blood flow, a significant increase in plasma amylase and lipase activity, plasma interleukin-1beta and interleukin-6 concentration, as well as, the development of the histological signs of pancreatic damage (edema, leukocyte infiltration, and vacuolization). Administration of HGF without induction of pancreatitis increased plasma interleukin-10. Treatment with HGF, during induction of pancreatitis, increased plasma interleukin-10 and attenuated the pancreatic damage, what was manifested by histological improvement of pancreatic integrity, the partial reversion of the drop in DNA synthesis and pancreatic blood flow, and the reduction in pancreatitis evoked increase in plasma amylase, lipase, and interleukin-1beta and interleukin-6 levels. HGF administrated at the dose 2 microg/kg exhibited a similar beneficial effect as administration of HGF at the doses 10 or 50 microg/kg. Treatment with HGF at the dose 0.4 microg/kg was less effective. We conclude that: (1) administration of HGF attenuates pancreatic damage in caerulein-induced pancreatitis; (2) this effect seems to be related to the increase in production of interleukin-10, the reduction in

  9. Herbal Formula, PM014, Attenuates Lung Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Lee, Hyojung; Kim, Youngeun; Kim, Hye Jin; Park, Soojin; Jang, Young Pyo; Jung, Sungki; Jung, Heejae; Bae, Hyunsu

    2012-01-01

    Chronic obstructive pulmonary disease (COPD), which is characterized by airway obstruction, leads to, as the two major forms of COPD, chronic bronchitis and emphysema. This study was conducted to evaluate the effects of herbal formula, PM014, in a murine model of COPD. Balb/c mice were treated once with each herb extract in PM014 or PM014 mixture via an oral injection. Lipopolysaccharide (LPS) or elastase/LPS were administrated to the mice to induce a disease that resembles COPD. PM014 treatment significantly attenuated the increased accumulation of immune cells in bronchoalveolar lavage fluid (BALF) compared to control mice. In addition, the TNF-α and IL-6 levels in BALF were decreased in the PM014 mice. Furthermore, histological analysis demonstrated that PM014 attenuated the hazardous effects of lung inflammation. These data suggest that PM014 exerts beneficial effects against forms of COPD such as lung inflammation. PMID:22778777

  10. Grape derived polyphenols attenuate tau neuropathology in a mouse model of Alzheimer's disease.

    PubMed

    Wang, Jun; Santa-Maria, Ismael; Ho, Lap; Ksiezak-Reding, Hanna; Ono, Kenjiro; Teplow, David B; Pasinetti, Giulio Maria

    2010-01-01

    Aggregation of microtubule-associated protein tau into insoluble intracellular neurofibrillary tangles is a characteristic hallmark of Alzheimer's disease (AD) and other neurodegenerative diseases, including progressive supranuclear palsy, argyrophilic grain disease, corticobasal degeneration, frontotemporal dementias with Parkinsonism linked to chromosome 17, and Pick's disease. Tau is abnormally hyperphosphorylated in AD and aberrant tau phosphorylation contributes to the neuropathology of AD and other tauopathies. Anti-aggregation and anti-phosphorylation are main approaches for tau-based therapy. In this study, we report that a select grape-seed polyphenol extract (GSPE) could potently interfere with the assembly of tau peptides into neurotoxic aggregates. Moreover, oral administration of GSPE significantly attenuated the development of AD type tau neuropathology in the brain of TMHT mouse model of AD through mechanisms associated with attenuation of extracellular signal-receptor kinase 1/2 signaling in the brain.

  11. Silymarin attenuates airway inflammation induced by cigarette smoke in mice.

    PubMed

    Li, Diandian; Xu, Dan; Wang, Tao; Shen, Yongchun; Guo, Shujin; Zhang, Xue; Guo, Lingli; Li, Xiaoou; Liu, Lian; Wen, Fuqiang

    2015-04-01

    Cigarette smoke (CS), which increases inflammation and oxidative stress, is a major risk factor for the development of COPD. In this study, we investigated the effects of silymarin, a polyphenolic flavonoid isolated from the seeds and fruits of milk thistle, on CS-induced airway inflammation and oxidative stress in mice and the possible mechanisms. BALB/c mice were exposed to CS for 2 h twice daily, 6 days per week for 4 weeks. Silymarin (25, 50 mg/kg·day) was administered intraperitoneally 1 h before CS exposure. Bronchoalveolar lavage fluid (BALF) was acquired for cell counting and the detection of pro-inflammatory cytokine levels. Lung tissue was collected for histological examination, myeloperoxidase (MPO) activity assay, superoxide dismutase (SOD) activities, and malondialdehyde (MDA) levels. The phosphorylation of ERK and p38 was evaluated by Western blotting. Pretreatment with silymarin significantly attenuated CS-induced thickening of the airway epithelium, peribronchial inflammatory cell infiltration, and lumen obstruction. The numbers of total cells, macrophages, and neutrophils, along with the MPO activity (a marker of neutrophil accumulation) in BALF, were remarkably decreased by silymarin in CS-exposed mice (all p<0.05). In addition, silymarin pretreatment dampened the secretion of TNF-α, IL-1β, and IL-8 in BALF. High-dose silymarin (50 mg/kg·day) administration also prevented CS-induced elevation in MDA levels and decrease in SOD activities (p<0.05). Furthermore, the CS-induced phosphorylation of ERK and p38 was also attenuated by silymarin (p<0.05). These results suggest that silymarin attenuated inflammation and oxidative stress induced by cigarette smoke. The anti-inflammatory effect might partly act through the mitogen-activated protein kinases (MAPK) pathway.

  12. Attention Wins over Sensory Attenuation in a Sound Detection Task

    PubMed Central

    Cao, Liyu; Gross, Joachim

    2015-01-01

    ‘Sensory attenuation’, i.e., reduced neural responses to self-induced compared to externally generated stimuli, is a well-established phenomenon. However, very few studies directly compared sensory attenuation with attention effect, which leads to increased neural responses. In this study, we brought sensory attenuation and attention together in a behavioural auditory detection task, where both effects were quantitatively measured and compared. The classic auditory attention effect of facilitating detection performance was replicated. When attention and sensory attenuation were both present, attentional facilitation decreased but remained significant. The results are discussed in the light of current theories of sensory attenuation. PMID:26302246

  13. Coenzyme Q10 Administration Increases Brain Mitochondrial Concentrations and Exerts Neuroprotective Effects

    NASA Astrophysics Data System (ADS)

    Matthews, Russell T.; Yang, Lichuan; Browne, Susan; Baik, Myong; Flint Beal, M.

    1998-07-01

    Coenzyme Q10 is an essential cofactor of the electron transport chain as well as a potent free radical scavenger in lipid and mitochondrial membranes. Feeding with coenzyme Q10 increased cerebral cortex concentrations in 12- and 24-month-old rats. In 12-month-old rats administration of coenzyme Q10 resulted in significant increases in cerebral cortex mitochondrial concentrations of coenzyme Q10. Oral administration of coenzyme Q10 markedly attenuated striatal lesions produced by systemic administration of 3-nitropropionic acid and significantly increased life span in a transgenic mouse model of familial amyotrophic lateral sclerosis. These results show that oral administration of coenzyme Q10 increases both brain and brain mitochondrial concentrations. They provide further evidence that coenzyme Q10 can exert neuroprotective effects that might be useful in the treatment of neurodegenerative diseases.

  14. Ultrasonic attenuation in pearlitic steel.

    PubMed

    Du, Hualong; Turner, Joseph A

    2014-03-01

    Expressions for the attenuation coefficients of longitudinal and transverse ultrasonic waves are developed for steel with pearlitic microstructure. This type of lamellar duplex microstructure influences attenuation because of the lamellar spacing. In addition, longitudinal attenuation measurements were conducted using an unfocused transducer with 10 MHz central frequency on the cross section of a quenched railroad wheel sample. The dependence of longitudinal attenuation on the pearlite microstructure is observed from the changes of longitudinal attenuation from the quenched tread surface to deeper locations. The results show that the attenuation value is lowest and relatively constant within the quench depth, then increases linearly. The experimental results demonstrate a reasonable agreement with results from the theoretical model. Ultrasonic attenuation provides an important non-destructive method to evaluate duplex microstructure within grains which can be implemented for quality control in conjunction with other manufacturing processes.

  15. Live attenuated vaccines for invasive Salmonella infections

    PubMed Central

    Tennant, Sharon M.; Levine, Myron M.

    2015-01-01

    Salmonella enterica serovar Typhi produces significant morbidity and mortality worldwide despite the fact that there are licensed S. Typhi vaccines available. This is primarily due to the fact that these vaccines are not used in the countries that most need them. There is growing recognition that an effective invasive Salmonella vaccine formulation must also prevent infection due to other Salmonella serovars. We anticipate that a multivalent vaccine that targets the following serovars will be needed to control invasive Salmonella infections worldwide: S. Typhi, S. Paratyphi A, S. Paratyphi B (currently uncommon but may become dominant again), S. Typhimurium, S. Enteritidis and S. Choleraesuis (as well as other Group C Salmonella). Live attenuated vaccines are an attractive vaccine formulation for use in developing as well as developed countries. Here, we describe the methods of attenuation that have been used to date to create live attenuated Salmonella vaccines and provide an update on the progress that has been made on these vaccines. PMID:25902362

  16. Live attenuated vaccines for invasive Salmonella infections.

    PubMed

    Tennant, Sharon M; Levine, Myron M

    2015-06-19

    Salmonella enterica serovar Typhi produces significant morbidity and mortality worldwide despite the fact that there are licensed Salmonella Typhi vaccines available. This is primarily due to the fact that these vaccines are not used in the countries that most need them. There is growing recognition that an effective invasive Salmonella vaccine formulation must also prevent infection due to other Salmonella serovars. We anticipate that a multivalent vaccine that targets the following serovars will be needed to control invasive Salmonella infections worldwide: Salmonella Typhi, Salmonella Paratyphi A, Salmonella Paratyphi B (currently uncommon but may become dominant again), Salmonella Typhimurium, Salmonella Enteritidis and Salmonella Choleraesuis (as well as other Group C Salmonella). Live attenuated vaccines are an attractive vaccine formulation for use in developing as well as developed countries. Here, we describe the methods of attenuation that have been used to date to create live attenuated Salmonella vaccines and provide an update on the progress that has been made on these vaccines.

  17. St. John's Wort Attenuates Colorectal Carcinogenesis in Mice through Suppression of Inflammatory Signaling.

    PubMed

    Manna, Soumen K; Golla, Srujana; Golla, Jaya Prakash; Tanaka, Naoki; Cai, Yan; Takahashi, Shogo; Krausz, Kristopher W; Matsubara, Tsutomu; Korboukh, Ilia; Gonzalez, Frank J

    2015-09-01

    Despite widespread use as well as epidemiologic indications, there have been no investigations into the effect of St. John's wort (SJW) extract on colorectal carcinogenesis in vivo. This study reports a systematic evaluation of the impact of dietary supplementation of SJW extract on azoxymethane-induced colorectal carcinogenesis in mice. Mice were fed with either AIN-93G (control) diet or SJW extract-supplemented diet (SJW diet) prior to azoxymethane treatment. SJW diet was found to significantly improve the overall survival of azoxymethane-treated mice. Pretreatment with the SJW diet significantly reduced body weight loss as well as decrease of serum albumin and cholesterol levels associated with azoxymethane-induced colorectal tumorigenesis. SJW diet-fed mice showed a significant decrease in tumor multiplicity along with a decrease in incidence of large tumors and a trend toward decreased total tumor volume in a dose-dependent manner. A short-term study, which examined the effect of SJW prior to rectal bleeding, also showed decrease in colorectal polyps in SJW diet-fed mice. Nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinase (ERK1/2) pathways were attenuated by SJW administration. SJW extract resulted in early and continuous attenuation of these pathways in the colon epithelium of SJW diet-fed mice under both short-term and long-term treatment regimens. In conclusion, this study demonstrated the chemopreventive potential of SJW extract against colorectal cancer through attenuation of proinflammatory processes.

  18. Dosing schedule-dependent attenuation of dexamethasone-induced muscle atrophy in mice.

    PubMed

    Nakao, Reiko; Yamamoto, Saori; Yasumoto, Yuki; Oishi, Katsutaka

    2014-05-01

    Many inflammatory and autoimmune diseases are treated using synthetic glucocorticoids. However, excessive glucocorticoid can often cause unpredictable effects including muscle atrophy. Endogenous glucocorticoid levels robustly fluctuate in a circadian manner and peak just before the onset of the active phase in both humans and nocturnal rodents. The present study determines whether muscle atrophy induced by exogenous glucocorticoid can be avoided by optimizing dosing times. We administered single daily doses of the glucocorticoid analog dexamethasone (Dex) to mice for 10 days at the times of day corresponding to peak (early night) or trough (early morning) endogenous glucocorticoid levels. Administration at the acrophase of endogenous glucocorticoids significantly attenuated Dex-induced wasting of the gastrocnemius (Ga) and tibialis anterior (TA) muscles that comprise mostly fast-twitch muscle fibers. Real-time RT-PCR revealed that the Dex-induced mRNA expression of genes encoding the atrophy-related ubiquitin ligases Muscle Atrophy F-box (Fbxo32, also known as MAFbx/Atrogin-1) and Muscle RING finger 1 (Trim63, also known as MuRF1) in the Ga and TA muscles was significantly attenuated by Dex when administered during the early night. Dex negligibly affected the weight of the soleus (So) muscle that mostly comprises slow-twitch muscle fibers, but significantly and similarly decreased the weight of the spleen at both dosing times. These results suggest that glucocorticoid-induced muscle atrophy can be attenuated by optimizing the dosing schedule.

  19. Royal jelly attenuates azathioprine induced toxicity in rats.

    PubMed

    Ahmed, Walaa M S; Khalaf, A A; Moselhy, Walaa A; Safwat, Ghada M

    2014-01-01

    In the present study, we investigated the potential protective effects of royal jelly against azathioprine-induced toxicity in rat. Intraperitoneal administration of azathioprine (50 mg/kgB.W.) induced a significant decrease in RBCs count, Hb concentration, PCV%, WBCs count, differential count and platelet count, hepatic antioxidant enzymes (reduced glutathione and glutathione s-transferase) and increase of serum transaminases (alanine aminotransferase and aspartate aminotransferase enzymes) activities, alkaline phosphatase and malondialdehyde formation. Azathioprine induced hepatotoxicity was reflected by marked pathological changes in the liver. Oral administration of royal jelly (200 mg/kgB.W.) was efficient in counteracting azathioprine toxicity whereas it altered the anemic condition, leucopenia and thrombocytopenia induced by azathioprine. Furthermore, royal jelly exerted significant protection against liver damage induced by azathioprine through reduction of the elevated activities of serum hepatic enzymes. Moreover, royal jelly blocked azathioprine-induced lipid peroxidation through decreasing the malondialdehyde formation. In conclusion, royal jelly possesses a capability to attenuate azathioprine-induced toxicity.

  20. Galacto‐oligosaccharides attenuate renal injury with microbiota modification

    PubMed Central

    Furuse, Satoshi U.; Ohse, Takamoto; Jo‐Watanabe, Airi; Shigehisa, Akira; Kawakami, Koji; Matsuki, Takahiro; Chonan, Osamu; Nangaku, Masaomi

    2014-01-01

    Abstracts Tubulointerstitial injury is central to the progression of end‐stage renal disease. Recent studies have revealed that one of the most investigated uremic toxins, indoxyl sulfate (IS), caused tubulointerstitial injury through oxidative stress and endoplasmic reticulum (ER) stress. Because indole, the precursor of IS, is synthesized from dietary tryptophan by the gut microbiota, we hypothesized that the intervention targeting the gut microbiota in kidney disease with galacto‐oligosaccharides (GOS) would attenuate renal injury. After 2 weeks of GOS administration for 5/6 nephrectomized (Nx) or sham‐operated (Sham) rats, cecal indole and serum IS were measured, renal injury was evaluated, and the effects of GOS on the gut microbiota were examined using pyrosequencing methods. Cecal indole and serum IS were significantly decreased and renal injury was improved with decreased infiltrating macrophages in GOS‐treated Nx rats. The expression levels of ER stress markers and apoptosis were significantly increased in the Nx rats and decreased with GOS. The microbiota analysis indicated that GOS significantly increased three bacterial families and decreased five families in the Nx rats. In addition, the analysis also revealed that the bacterial family Clostridiaceae was significantly increased in the Nx rats compared with the Sham rats and decreased with GOS. Taken altogether, our data show that GOS decreased cecal indole and serum IS, attenuated renal injury, and modified the gut microbiota in the Nx rats, and that the gut microbiota were altered in kidney disease. GOS could be a novel therapeutic agent to protect against renal injury. PMID:24994892

  1. Engineering Administration.

    ERIC Educational Resources Information Center

    Naval Personnel Program Support Activity, Washington, DC.

    This book is intended to acquaint naval engineering officers with their duties in the engineering department. Standard shipboard organizations are analyzed in connection with personnel assignments, division operations, and watch systems. Detailed descriptions are included for the administration of directives, ship's bills, damage control, training…

  2. Administrative IT

    ERIC Educational Resources Information Center

    Grayson, Katherine, Ed.

    2006-01-01

    When it comes to Administrative IT solutions and processes, best practices range across the spectrum. Enterprise resource planning (ERP), student information systems (SIS), and tech support are prominent and continuing areas of focus. But widespread change can also be accomplished via the implementation of campuswide document imaging and sharing,…

  3. Database Administrator

    ERIC Educational Resources Information Center

    Moore, Pam

    2010-01-01

    The Internet and electronic commerce (e-commerce) generate lots of data. Data must be stored, organized, and managed. Database administrators, or DBAs, work with database software to find ways to do this. They identify user needs, set up computer databases, and test systems. They ensure that systems perform as they should and add people to the…

  4. The Kinetics of Intramolecular Distribution of 15N in Uric Acid after Administration of [15N]Glycine A REAPPRAISAL OF THE SIGNIFICANCE OF PREFERENTIAL LABELING OF N-(3 + 9) OF URIC ACID IN PRIMARY GOUT

    PubMed Central

    Sperling, Oded; Wyngaarden, James B.; Starmer, C. Frank

    1973-01-01

    The concept of an abnormality of glutamine metabolism in primary gout was first proposed on the basis of isotope data: when [15N]glycine was administered to gouty subjects, there was disproportionately great enrichment of N-(3 + 9) of uric acid, which derive from the amide-N of glutamine. An unduly high concentration of 15N in glutamine was postulated, and attributed to a hypothetical defect in catabolism of glutamine. Excess glutamine was proposed as the driving force of uric acid overproduction. We have reexamined this proposition in four gouty subjects: one mild overproducer of uric acid with “idiopathic gout,” one marked overproducer with high-grade but “partial” hypoxanthine-guanine phosphoribosyl-transferase deficiency, and two extraordinary overproducers with superactive phosphoribosylpyrophosphate synthetases. In the last three, the driving force of excessive purine biosynthesis is a known surplus of α-5-phosphoribosyl-1-pyrophosphate. Disproportionately high labeling of N-(3 + 9) was present in all four gouty subjects, most marked in the most flamboyant overproducers. The precursor glucine pool was sampled by periodic administration of benzoic acid and isolation of urinary hippuric acid. Similarly, the precursor glutamine pool was sampled by periodic administration of phenylacetic acid and isolation of the amide-N of urinary phenylacetylglutamine. The time course of 15N enrichment of hippurate differed from that of the amide-N of glutamine. Whereas initial enrichment values of hippurate were very high, those of glutamine-amide-N were low, increasing to a maximum at about 3 h, and then declining less rapidly than those of hippurate. However, enrichment values of hippurate and of phenacetyl glutamine were normal in all of the gouty subjects studied. Thus, preferential enrichment of N-(3 + 9) in gouty overproducers given [15N]glycine does not necessarily reflect a specific abnormality of glutamine metabolism, but rather appears to be a kinetic

  5. Effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart.

    PubMed

    Kansal, Sunil Kumar; Jyoti, Uma; Sharma, Samridhi; Kaura, Arun; Deshmukh, Rahul; Goyal, Sandeep

    2015-06-01

    Hyperlipidemia is regarded as independent risk factor in the development of ischemic heart disease, and it can increase the myocardial susceptibility to ischemia-/reperfusion (I/R)-induced injury. Hyperlipidemia attenuates the cardioprotective response of ischemic preconditioning (IPC). The present study investigated the effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat hearts. Hyperlipidemia was induced in rat by feeding high-fat diet (HFD) for 6 weeks then the serum lipid profile was observed. In experiment, the isolated Langendorff rat heart preparation was subjected to 4 cycles of ischemic preconditioning (IPC), then 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was elaborated morphologically by triphenyltetrazolium chloride (TTC) staining and biochemically by lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) release from coronary effluent and left ventricular collagen content. However, the effect of zinc supplement, i.e., zinc pyrithione (10 μM) perfused during reperfusion for 120 min, significantly abrogated the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart whereas administration of chelator of this zinc ionophore, i.e., N,N,N',N'-tetrakis(2-pyridylmethyl)ethylene diamine (TPEN; 10 μM), perfused during reperfusion 2 min before the perfusion of zinc pyrithione abrogated the cardioprotective effect of zinc supplement during experiment in hyperlipidemic rat heart. Thus, the administration of zinc supplements limits the infarct size, LDH, and CK-MB and enhanced the collagen level which suggests that the attenuated cardioprotective effect of IPC in hyperlipidemic rat is due to zinc loss during reperfusion caused by ischemia/reperfusion.

  6. Live attenuated B. pertussis as a single-dose nasal vaccine against whooping cough.

    PubMed

    Mielcarek, Nathalie; Debrie, Anne-Sophie; Raze, Dominique; Bertout, Julie; Rouanet, Carine; Younes, Amena Ben; Creusy, Colette; Engle, Jacquelyn; Goldman, William E; Locht, Camille

    2006-07-01

    Pertussis is still among the principal causes of death worldwide, and its incidence is increasing even in countries with high vaccine coverage. Although all age groups are susceptible, it is most severe in infants too young to be protected by currently available vaccines. To induce strong protective immunity in neonates, we have developed BPZE1, a live attenuated Bordetella pertussis strain to be given as a single-dose nasal vaccine in early life. BPZE1 was developed by the genetic inactivation or removal of three major toxins. In mice, BPZE1 was highly attenuated, yet able to colonize the respiratory tract and to induce strong protective immunity after a single nasal administration. Protection against B. pertussis was comparable to that induced by two injections of acellular vaccine (aPV) in adult mice, but was significantly better than two administrations of aPV in infant mice. Moreover, BPZE1 protected against Bordetella parapertussis infection, whereas aPV did not. BPZE1 is thus an attractive vaccine candidate to protect against whooping cough by nasal, needle-free administration early in life, possibly at birth.

  7. Live Attenuated B. pertussis as a Single-Dose Nasal Vaccine against Whooping Cough

    PubMed Central

    Mielcarek, Nathalie; Debrie, Anne-Sophie; Raze, Dominique; Bertout, Julie; Rouanet, Carine; Younes, Amena Ben; Creusy, Colette; Engle, Jacquelyn; Goldman, William E; Locht, Camille

    2006-01-01

    Pertussis is still among the principal causes of death worldwide, and its incidence is increasing even in countries with high vaccine coverage. Although all age groups are susceptible, it is most severe in infants too young to be protected by currently available vaccines. To induce strong protective immunity in neonates, we have developed BPZE1, a live attenuated Bordetella pertussis strain to be given as a single-dose nasal vaccine in early life. BPZE1 was developed by the genetic inactivation or removal of three major toxins. In mice, BPZE1 was highly attenuated, yet able to colonize the respiratory tract and to induce strong protective immunity after a single nasal administration. Protection against B. pertussis was comparable to that induced by two injections of acellular vaccine (aPV) in adult mice, but was significantly better than two administrations of aPV in infant mice. Moreover, BPZE1 protected against Bordetella parapertussis infection, whereas aPV did not. BPZE1 is thus an attractive vaccine candidate to protect against whooping cough by nasal, needle-free administration early in life, possibly at birth. PMID:16839199

  8. Patient self-attenuation and technologist dose in positron emission tomography

    SciTech Connect

    Zeff, Benjamin W.; Yester, Michael V.

    2005-04-01

    Positron emission tomography (PET), with 511-keV radiation and long patient-uptake times, presents unique radiation safety concerns. This two-part study considers aspects of PET radiation safety as they relate to PET suite design, dose to the public, and technologist occupational dose. In the first part of the study, the self-attenuation of radiation by patients' bodies was quantified. The radiation exposure was measured at three positions from 64 patients injected with fluorine-18 fluorodeoxyglucose (FDG) during the uptake period. Compared with an in vitro control used as a point source, a significant decrease in exposure (>40% at 1 m) was observed due to nonuniform distribution of FDG and attenuation within the patients. The attenuation data are consistent with results from simulations [M. E. Phelps, ''Comments and Perspectives,'' J. Nucl. Med. 45, 1601 (2004)] that treat the body as a uniform, water-filled cylinder. As distance is often the principal source of protection for 511-keV radiation, the considerable self-attenuation may allow for more compact PET suites. However, despite high patient self-attenuation, shielding, and standard precautionary measures, PET technologist occupational doses can remain quite high ({approx}12 mSv/year). The second part of this study tracked the daily dose received by PET technologists. Close technologist-patient interaction both during and following FDG administration, as much as 20 min/study, contribute to the high doses and point to the need for a more innovative approach to radiation protection for PET technologists.

  9. l-Scoulerine attenuates behavioural changes induced by methamphetamine in zebrafish and mice.

    PubMed

    Mi, Guiyun; Gao, Yunyun; Yan, Hui; Jin, Xiao; Ye, Enmao; Liu, Shuai; Gong, Zehui; Yang, Hongju; Yang, Zheng

    2016-02-01

    Methamphetamine (METH), a substance with a high potential for abuse and addiction, is a serious worldwide public health problem. METH addicts often show extreme paranoia, anxiety, and depression. Thus, there is no effective medication for the treatment of METH-induced abnormalities. In the present study, we investigated the effects of l-Scoulerine (l-SLR), a tetrahydroprotoberberine (THPBS) alkaloid, on METH-induced anxiety-like behaviour in zebrafish and METH-induced addictive behavior in mice. In the novel tank test, acute administration of METH (2 mg/L) induced a significant decrease in the number of total vertical transitions and time spent in the upper zone. Moreover, METH produced significant avoidance behaviour showing increased swimming time in the central area and high speed movement in the mirror area in the mirror stimulation test; these anxiety-like changes were attenuated by l-SLR. Chronic administration of METH (2 mg/kg) produced a steady increase in locomotor activity and conditioned place preference in mice. l-SLR (5 mg/kg) failed to reduce acute METH-induced hyperlocomotion, but attenuated chronic METH-induced behavioural sensitization and significantly blocked the expression of conditioned place preference induced by METH in mice. The present study suggests that l-SLR may be a promising agent for the treatment of addiction and anxiety induced by METH.

  10. 49 CFR 227.117 - Hearing protector attenuation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... protector attenuation for the specific noise environments in which the protector will be used. The railroad... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION OCCUPATIONAL NOISE EXPOSURE Occupational Noise Exposure for Railroad...-evaluated whenever employee noise exposures increase to the extent that the hearing protectors provided...

  11. Emetine Di-HCl Attenuates Type 1 Diabetes Mellitus in Mice

    PubMed Central

    Hudson, LaQueta K; Dancho, Meghan E; Li, Jianhua; Bruchfeld, Johanna B; Ragab, Ahmed A; He, Mingzhu M; Bragg, Meaghan; Lenaghan, Delaney; Quinn, Michael D; Fritz, Jason R; Tanzi, Matthew V; Silverman, Harold A; Hanes, William M; Levine, Yaakov A; Pavlov, Valentin A; Olofsson, Peder S; Roth, Jesse; Al-Abed, Yousef; Andersson, Ulf; Tracey, Kevin J; Chavan, Sangeeta S

    2016-01-01

    Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease characterized by β cell destruction, insulin deficiency and hyperglycemia. Activated macrophages and autoimmune T cells play a crucial role in the pathogenesis of hyperglycemia in NOD murine diabetes models, but the molecular mechanisms of macrophage activation are unknown. We recently identified pigment epithelium-derived factor (PEDF) as an adipocyte-derived factor that activates macrophages and mediates insulin resistance. Reasoning that PEDF might participate as a proinflammatory mediator in murine diabetes, we measured PEDF levels in NOD mice. PEDF levels are significantly elevated in pancreas, in parallel with pancreatic TNF levels in NOD mice. To identify experimental therapeutics, we screened 2,327 compounds in two chemical libraries (the NIH Clinical Collection and Pharmakon-1600) for leads that inhibit PEDF mediated TNF release in macrophage cultures. The lead molecule selected, “emetine” is a widely used emetic. It inhibited PEDF-mediated macrophage activation with an EC50 or 146 nmol/L. Administration of emetine to NOD mice and to C57Bl6 mice subjected to streptozotocin significantly attenuated hyperglycemia, reduced TNF levels in pancreas and attenuated insulitis. Together, these results suggest that targeting PEDF with emetine may attenuate TNF release and hyperglycemia in murine diabetes models. This suggests that further investigation of PEDF and emetine in the pathogenesis of human diabetes is warranted. PMID:27341452

  12. Bees' Honey Attenuation of Metanil-Yellow-Induced Hepatotoxicity in Rats

    PubMed Central

    Al-Malki, Abdulrahman L.; Sayed, Ahmed Amir Radwan

    2013-01-01

    The present study aims to investigate the protective effect of bees' honey against metanil-yellow-induced hepatotoxicity in rats. Rats were divided into 7 groups: control group; three groups treated with 50, 100, and 200 mg/kg metanil yellow, and three groups treated with metanil yellow plus 2.5 mg · kg−1 · day−1 bees' honey for 8 weeks. The obtained data showed that the antioxidant/anti-inflammatory activity of bees' honey reduced the oxidative stress in the liver tissue and downregulated the inflammatory markers. In addition, the elevated levels of AGE and the activated NF-κB in the metanil-yellow-treated animals were significantly attenuated. Moreover, the levels of TNF-α and IL-1β were significantly attenuated as a result of bees' honey administration. Furthermore, the histopathological examination of the liver showed that bees' honey reduced fatty degeneration, cytoplasmic vacuolization, and necrosis in metanil-yellow-treated rats. In conclusion, the obtained data suggest that bees' honey has hepatoprotective effect on acute liver injuries induced by metanil-yellow in vivo, and the results suggested that the effect of bees' honey against metanil yellow-induced liver damage is related to its antioxidant/anti-inflammatory properties which attenuate the activation of NF-κB and its controlled genes like TNF-α and IL-1β. PMID:23818929

  13. Ultrasonic Attenuation in Zircaloy-4

    SciTech Connect

    Gomez, M.P.; Banchik, A.D.; Lopez Pumarega, M.I.; Ruzzante, J.E.

    2005-04-09

    In this work the relationship between Zircaloy-4 grain size and ultrasonic attenuation behavior was studied for longitudinal waves in the frequency range of 10-90 MHz. The attenuation was analyzed as a function of frequency for samples with different mechanical and heat treatments having recrystallized and Widmanstatten structures with different grain size. The attenuation behavior was analyzed by different scattering models, depending on grain size, wavelength and frequency.

  14. Attenuation of Cavity Bay Noise

    DTIC Science & Technology

    2012-10-01

    amplification, known as peaking. Overall, the palliative devices based on resonant arrays have demonstrated high levels of attenuation which are...when the resonant frequency condition is met. The attenuation from a Helmholtz type resonator is achieved through frictional losses, vortex shedding...3 the λ/4 condition can be fulfilled and therefore porous mesh devices may not be able to provide a high level of attenuation . Resonant arrays

  15. LINE-ABOVE-GROUND ATTENUATOR

    DOEpatents

    Wilds, R.B.; Ames, J.R.

    1957-09-24

    The line-above-ground attenuator provides a continuously variable microwave attenuator for a coaxial line that is capable of high attenuation and low insertion loss. The device consists of a short section of the line-above- ground plane type transmission lime, a pair of identical rectangular slabs of lossy material like polytron, whose longitudinal axes are parallel to and indentically spaced away from either side of the line, and a geared mechanism to adjust amd maintain this spaced relationship. This device permits optimum fineness and accuracy of attenuator control which heretofore has been difficult to achieve.

  16. Effect of Magnesium Sulfate and Clonidine in Attenuating Hemodynamic Response to Pneumoperitoneum in Laparoscopic Cholecystectomy

    PubMed Central

    Kamble, Shruthi P.; Bevinaguddaiah, Yatish; Nagaraja, Dinesh Chillkunda; Pujar, Vinayak S.; Anandaswamy, Tejesh C.

    2017-01-01

    Background: Pneumoperitoneum in laparoscopic procedures is associated with hemodynamic response, due to the release of catecholamines and vasopressin. Magnesium and clonidine have been used to attenuate such hemodynamic responses by inhibiting release of these mediators. We conducted this randomized, double-blinded study to assess which of the two attenuates hemodynamic response better. Materials and Methods: Ninety American Society of Anesthesiologists health status Classes I and II patients posted for elective laparoscopic cholecystectomy were randomized into three groups of thirty patients each. Group C received injection clonidine 1 μg/kg diluted in 10 mL normal saline over 10 min, prior to pneumoperitoneum. Group M received injection magnesium sulfate 50 mg/kg diluted in 10 mL normal saline over 10 min, prior to pneumoperitoneum. Group NS received 10 mL normal saline intravenously over 10 min, prior to pneumoperitoneum. Hemodynamic parameters were recorded before induction (baseline values), at the end of magnesium sulfate/clonidine/saline administration and before pneumoperitoneum (P0), 5 min (P5), 10 min (P10), 20 min (P20), 30 min (P30), and 40 min (P40) after pneumoperitoneum. Results: Systolic blood pressure, diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were all significantly higher in the normal saline group compared to magnesium and clonidine. On comparing patients in Group M and Group C, DBP, MAP, and HR were significantly lower in the magnesium group. Mean extubation time and time to response to verbal commands were significantly longer in the magnesium group. Conclusions: Both magnesium and clonidine attenuated the hemodynamic response to pneumoperitoneum. However, magnesium 50 mg/kg, attenuated hemodynamic response better than clonidine 1 μg/kg. PMID:28298759

  17. Development of Live-Attenuated Arenavirus Vaccines Based on Codon Deoptimization

    PubMed Central

    Cheng, Benson Yee Hin; Ortiz-Riaño, Emilio; Nogales, Aitor

    2015-01-01

    ABSTRACT Arenaviruses have a significant impact on public health and pose a credible biodefense threat, but the development of safe and effective arenavirus vaccines has remained elusive, and currently, no Food and Drug Administration (FDA)-licensed arenavirus vaccines are available. Here, we explored the use of a codon deoptimization (CD)-based approach as a novel strategy to develop live-attenuated arenavirus vaccines. We recoded the nucleoprotein (NP) of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) with the least frequently used codons in mammalian cells, which caused lower LCMV NP expression levels in transfected cells that correlated with decreased NP activity in cell-based functional assays. We used reverse-genetics approaches to rescue a battery of recombinant LCMVs (rLCMVs) encoding CD NPs (rLCMV/NPCD) that showed attenuated growth kinetics in vitro. Moreover, experiments using the well-characterized mouse model of LCMV infection revealed that rLCMV/NPCD1 and rLCMV/NPCD2 were highly attenuated in vivo but, upon a single immunization, conferred complete protection against a subsequent lethal challenge with wild-type (WT) recombinant LCMV (rLCMV/WT). Both rLCMV/NPCD1 and rLCMV/NPCD2 were genetically and phenotypically stable during serial passages in FDA vaccine-approved Vero cells. These results provide proof of concept of the safety, efficacy, and stability of a CD-based approach for developing live-attenuated vaccine candidates against human-pathogenic arenaviruses. IMPORTANCE Several arenaviruses cause severe hemorrhagic fever in humans and pose a credible bioterrorism threat. Currently, no FDA-licensed vaccines are available to combat arenavirus infections, while antiarenaviral therapy is limited to the off-label use of ribavirin, which is only partially effective and is associated with side effects. Here, we describe the generation of recombinant versions of the prototypic arenavirus LCMV encoding codon-deoptimized viral

  18. Gamma-glutamylcysteinylethyl ester attenuates progression of carbon tetrachloride-induced acute liver injury in mice.

    PubMed

    Nishida, K; Ohta, Y; Ishiguro, I

    1998-02-20

    We examined the effect of gamma-glutamylcysteinylethyl ester (gamma-GCE), which is readily transported into hepatocytes and increases hepatocellular reduced glutathione (GSH) levels, on the progression of carbon tetrachloride (CCl4)-induced liver injury in mice in comparison with that of GSH. Administration of more than 160 micromol/kg of gamma-GCE, but not GSH, to mice at 3 h after intraperitoneal injection of CCl4 (1 ml/kg) significantly attenuated increases in serum aspartate aminotransferase and alanine aminotransferase activities at 24 h after the CCl4 injection. Increases in hepatic lipid peroxide (LPO) concentrations and decreases in hepatic GSH concentrations after the CCl4 injection were significantly diminished by the gamma-GCE (160 micromol/kg) administration, but not by the same dose of GSH. Gamma-GCE, gamma-glutamylcysteine, and cysteine acted as substrates for glutathione peroxidases much less efficiently than GSH in the post-mitochondrial fraction of normal mouse liver cells. These results indicate that gamma-GCE attenuates the progression of CCl4-induced acute liver injury in mice through the maintenance of hepatic GSH levels, leading to inhibition of hepatic LPO formation, which could be due to an efficient utilization of GSH converted from gamma-GCE in the liver cells.

  19. Suicide Risk: Amplifiers and Attenuators.

    ERIC Educational Resources Information Center

    Plutchik, Robert; Van Praag, Herman M.

    1994-01-01

    Attempts to integrate findings on correlates of suicide and violent risk in terms of a theory called a two-stage model of countervailing forces, which assumes that the strength of aggressive impulses is modified by amplifiers and attenuators. The vectorial interaction of amplifiers and attenuators creates an unstable equilibrium making prediction…

  20. Adjustable Optical-Fiber Attenuator

    NASA Technical Reports Server (NTRS)

    Buzzetti, Mike F.

    1994-01-01

    Adjustable fiber-optic attenuator utilizes bending loss to reduce strength of light transmitted along it. Attenuator functions without introducing measurable back-reflection or insertion loss. Relatively insensitive to vibration and changes in temperature. Potential applications include cable television, telephone networks, other signal-distribution networks, and laboratory instrumentation.

  1. Seismic attenuation of the inner core: Viscoelastic or stratigraphic?

    USGS Publications Warehouse

    Cormier, V.F.; Xu, L.; Choy, G.L.

    1998-01-01

    Broadband velocity waveforms of PKIKP in the distance range 150??to 180??are inverted for inner core attenuation. A mean Q?? of 244 is determined at 1 Hz from 8 polar and 9 equatorial paths. The scatter in measured Q-1 exceeds individual error estimates, suggesting significant variation in attenuation with path. These results are interpreted by (1) viscoelasticity, in which the relaxation spectrum has a low-frequency corner near or slightly above the frequency band of short-period body waves, and by (2) stratigraphic (scattering) attenuation, in which attenuation and pulse broadening are caused by the interference of scattered multiples in a velocity structure having rapid fluctuations along a PKIKP path. In the scattering interpretation, PKIKP attenuation is only weakly affected by the intrinsic shear attenuation measured in the free-oscillation band. Instead, its frequency dependence, path variations, and fluctuations are all explained by scattering attenuation in a heterogeneous fabric resulting from solidification texturing of intrinsically anisotropic iron. The requisite fabric may consist of either single or ordered groups of crystals with P velocity differences of at least 5% and as much as 12% between two crystallographic axes at scale lengths of 0.5 to 2 km in the direction parallel to the axis of rotation and longer in the cylindrically radial direction, perpendicular to the axis of rotation.Broadband velocity waveforms of PKIKP in the distance range 150?? to 180?? are inverted for inner core attenuation. A mean Q?? of 244 is determined at 1 Hz from 8 polar and 9 equatorial paths. The scatter in the measured Q-1 exceeds individual error estimates, indicating significant variation in attenuation with path. The results are interpreted by viscoelasticity and stratigraphic (scattering) attenuation.

  2. Seismic attenuation in multi-phase coexistence regions

    NASA Astrophysics Data System (ADS)

    Matas, J.; Ricard, Y. R.; Chambat, F.; Durand, S.

    2009-12-01

    Accurate description of seismic attenuation in the mantle becomes an increasingly important ingredient for realistic modeling of mantle structure. While seismological studies focused on globally dominant shear attenuation, only little is known about the compressional attenuation. In the mantle, structural transformations of mineralogical phases, associated with significant density increase, occur across regions having a finite width. Inside these regions, the elastic bulk modulus sampled by seismic waves differs significantly from the long-term bulk modulus seen by a viscous flow. The long-term incompressibility may be very low because of the density change related to various phase changes. We discuss differences between the classical theory of sound attenuation in a reacting fluid and the case of seismic propagation in a two-phase loop. A simple analytical model of a two-phase loop is developed to show that phase change should affect, both the bulk and the shear attenuation. The amplitude of this effect is comparable for both quantities. It implies that the seismic attenuation may be locally very diffrent from the usually adopted values. We show that attenuation occurs over two different time scales. Based on estimations of the phase kinetics in the case of the olivine-wadsleyite phase change, the low frequency attenuation occurs for periods larger than hundreds of years but the high frequency band occurs between 1 min and 1 hour in the domain of surface waves and seismic modes. We predict a minimum attenuation quality factor between 1-10 in the middle of the phase loop. However, kinetic rates of mantle phase transitions are not well known. We argue that measured normal mode attenuation can be used to put additional constrains on the phase change kinetics. Assuming a 10 km thickness of the olivine-to-wadsleyite phase transition, its kinetic rate should be either smaller than 11 seconds or greater than 11 minutes.

  3. Puerarin attenuates learning and memory impairments and inhibits oxidative stress in STZ-induced SAD mice.

    PubMed

    Zhao, Shan-shan; Yang, Wei-na; Jin, Hui; Ma, Kai-ge; Feng, Gai-feng

    2015-12-01

    Puerarin (PUE), an isoflavone purified from the root of Pueraria lobata (Chinese herb), has been reported to attenuate learning and memory impairments in the transgenic mouse model of Alzheimer's disease (AD). In the present study, we tested PUE in a sporadic AD (SAD) mouse model which was induced by the intracerebroventricular injection of streptozotocin (STZ). The mice were administrated PUE (25, 50, or 100mg/kg/d) for 28 days. Learning and memory abilities were assessed by the Morris water maze test. After behavioral test, the biochemical parameters of oxidative stress (glutathione peroxidase (GSH-Px), superoxide dismutases (SOD), and malondialdehyde (MDA)) were measured in the cerebral cortex and hippocampus. The SAD mice exhibited significantly decreased learning and memory ability, while PUE attenuated these impairments. The activities of GSH-Px and SOD were decreased while MDA was increased in the SAD animals. After PUE treatment, the activities of GSH-Px and SOD were elevated, and the level of MDA was decreased. The middle dose PUE was more effective than others. These results indicate that PUE attenuates learning and memory impairments and inhibits oxidative stress in STZ-induced SAD mice. PUE may be a promising therapeutic agent for SAD.

  4. Pharmacologic Antagonism of Ghrelin Receptors Attenuates Development of Nicotine Induced Locomotor Sensitization in Rats

    PubMed Central

    Wellman, Paul J.; Clifford, P. Shane; Rodriguez, Juan; Hughes, Samuel; Eitan, Shoshana; Brunel, Luc; Fehrentz, Jean-Alain; Martinez, Jean

    2011-01-01

    Aims Ghrelin (GHR) is an orexigenic gut peptide that interacts with ghrelin receptors (GHR-Rs) to modulate brain reinforcement circuits. Systemic GHR infusions augment cocaine stimulated locomotion and conditioned place preference (CPP) in rats, whereas genetic or pharmacological ablation of GHR-Rs has been shown to attenuate the acute locomotor-enhancing effects of nicotine, cocaine, amphetamine and alcohol and to blunt the CPP induced by food, alcohol, amphetamine and cocaine in mice. The stimulant nicotine can induce CPP and like amphetamine and cocaine, repeated administration of nicotine induces locomotor sensitization in rats. A key issue is whether pharmacological antagonism of GHR-Rs would similarly attenuate nicotine-induced locomotor sensitization. Method To examine the role of GHR-Rs in the behavioral sensitizing effects of nicotine, adult male rats were injected with either 0, 3 or 6 mg/kg of the GHR-R receptor antagonist JMV 2959 (i.p.) and 20 minutes later with either vehicle or 0.4 mg/kg nicotine hydrogen tartrate (s.c.) on each of 7 consecutive days. Results Rats treated with nicotine alone showed robust locomotor sensitization, whereas rats pretreated with JMV 2959 showed significantly attenuated nicotine-induced hyperlocomotion. Conclusions These results suggest that GHR-R activity is required for the induction of locomotor sensitization to nicotine and complement an emerging literature implicating central GHR systems in drug reward/reinforcement. PMID:21903141

  5. Ketanserin, a 5-HT2 receptor antagonist, decreases nicotine self-administration in rats.

    PubMed

    Levin, Edward D; Slade, Susan; Johnson, Michael; Petro, Ann; Horton, Kofi; Williams, Paul; Rezvani, Amir H; Rose, Jed E

    2008-12-14

    Nicotine intake constitutes a principal mechanism for tobacco addiction. In addition to primary effects on nicotinic acetylcholine receptors, nicotine has cascading effects, which may also underlie its neurobehavioral actions. Nicotine induces serotonin (5-HT) release, which has not classically been thought to be involved in tobacco addiction as dopamine has. However, addiction can be characterized more as a disorder of compulsion than a disorder of enjoyment. 5-HT mechanisms play key roles in compulsive disorders. Nicotine-induced 5-HT release may be a key to tobacco addiction. Ketanserin, a 5-HT2a and 5-HT2c receptor antagonist, significantly attenuates nicotine effects on attention and memory. These studies were conducted to determine if ketanserin would reduce nicotine self-administration in rats. Male Sprague-Dawley rats (N=12) were given initial food pellet training and then 10 sessions of nicotine self-administration training (0.03 mg/kg/infusion, i.v.). Then the rats were administered ketanserin (1 or 2 mg/kg, s.c.) or the saline vehicle. Ketanserin (2 mg/kg) significantly decreased nicotine self-administration. This did not seem to be due to sedative or amnestic effects of ketanserin. In a second study, the effects of repeated administration of 2 mg/kg ketanserin (N=11) vs. saline injections (N=10) were examined. In the initial phase, the acute effectiveness of ketanserin in significantly reducing nicotine self-administration was replicated. The effect became attenuated during the following several sessions, but the significant effect became re-established during the final phases of this two-week study. 5-HT mechanisms play critical roles in the maintenance of nicotine self-administration. Better understanding of those roles may help lead to new 5-HT-based treatments for tobacco addiction.

  6. Des-Aspartate-Angiotensin I Attenuates Mortality of Mice Exposed to Gamma Radiation via a Novel Mechanism of Action.

    PubMed

    Wang, Hong; Sethi, Gautam; Loke, Weng-Keong; Sim, Meng-Kwoon

    2015-01-01

    ACE inhibitors and ARBs (angiotensin receptor blockers) have been shown to attenuate radiation injuries in animal models of lethal gamma irradiation. These two classes of drug act by curtailing the actions of angiotensin II-linked inflammatory pathways that are up-regulated during gamma radiation in organ systems such as the brain, lung, kidney, and bone marrow. ACE inhibitors inhibit ACE and attenuate the formation of angiotensin II from angiotensin I; ARBs block the angiotensin AT1 receptor and attenuate the actions of angiotensin II that are elicited through the receptor. DAA-I (des-aspartate-angiotensin I), an orally active angiotensin peptide, also attenuates the deleterious actions of angiotensin II. It acts as an agonist on the angiotensin AT1 receptor and elicits responses that oppose those of angiotensn II. Thus, DAA-I was investigated for its anticipated radioprotection in gamma irradiated mice. DAA-I administered orally at 800 nmole/kg/day for 30 days post exposure (6.4 Gy) attenuated the death of mice during the 30-day period. The attenuation was blocked by losartan (50 nmole/kg/day, i.p.) that was administered sequential to DAA-I administration. This shows that the radioprotection was mediated via the angiotensin AT1 receptor. Furthermore, the radioprotection correlated to an increase in circulating PGE2 of surviving animals, and this suggests that PGE2 is involved in the radioprotection in DAA-I-treated mice. At the hematopoietic level, DAA-I significantly improved two syndromes of myelosuppression (leucopenia and lymphocytopenia), and mice pre-treated with DAA-I prior to gamma irradiation showed significant improvement in the four myelodysplastic syndromes that were investigated, namely leucopenia, lymphocytopenia, monocytopenia and thrombocytopenia. Based on the known ability of PGE2 to attenuate the loss of functional hematopoietic stem and progenitor cells in radiation injury, we hypothesize that PGE2 mediated the action of DAA-I. DAA-I completely

  7. Des-Aspartate-Angiotensin I Attenuates Mortality of Mice Exposed to Gamma Radiation via a Novel Mechanism of Action

    PubMed Central

    Wang, Hong; Sethi, Gautam; Loke, Weng-Keong; Sim, Meng-Kwoon

    2015-01-01

    ACE inhibitors and ARBs (angiotensin receptor blockers) have been shown to attenuate radiation injuries in animal models of lethal gamma irradiation. These two classes of drug act by curtailing the actions of angiotensin II-linked inflammatory pathways that are up-regulated during gamma radiation in organ systems such as the brain, lung, kidney, and bone marrow. ACE inhibitors inhibit ACE and attenuate the formation of angiotensin II from angiotensin I; ARBs block the angiotensin AT1 receptor and attenuate the actions of angiotensin II that are elicited through the receptor. DAA-I (des-aspartate-angiotensin I), an orally active angiotensin peptide, also attenuates the deleterious actions of angiotensin II. It acts as an agonist on the angiotensin AT1 receptor and elicits responses that oppose those of angiotensn II. Thus, DAA-I was investigated for its anticipated radioprotection in gamma irradiated mice. DAA-I administered orally at 800 nmole/kg/day for 30 days post exposure (6.4 Gy) attenuated the death of mice during the 30-day period. The attenuation was blocked by losartan (50 nmole/kg/day, i.p.) that was administered sequential to DAA-I administration. This shows that the radioprotection was mediated via the angiotensin AT1 receptor. Furthermore, the radioprotection correlated to an increase in circulating PGE2 of surviving animals, and this suggests that PGE2 is involved in the radioprotection in DAA-I-treated mice. At the hematopoietic level, DAA-I significantly improved two syndromes of myelosuppression (leucopenia and lymphocytopenia), and mice pre-treated with DAA-I prior to gamma irradiation showed significant improvement in the four myelodysplastic syndromes that were investigated, namely leucopenia, lymphocytopenia, monocytopenia and thrombocytopenia. Based on the known ability of PGE2 to attenuate the loss of functional hematopoietic stem and progenitor cells in radiation injury, we hypothesize that PGE2 mediated the action of DAA-I. DAA-I completely

  8. Flavocoxid attenuates gentamicin-induced nephrotoxicity in rats.

    PubMed

    El-Kashef, Dalia H; El-Kenawi, Asmaa E; Suddek, Ghada M; Salem, Hatem A

    2015-12-01

    Gentamicin is a widely used antibiotic against serious and life-threatening infections; however, its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine whether flavocoxid has a protective effect against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of flavocoxid on gentamicin induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was determined. Twenty-four male Wistar albino rats were randomly divided into three groups, namely control, gentamicin (100 mg/kg, i.p.) and gentamicin plus flavocoxid (20 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood, urine samples and kidneys were collected for further analysis. Gentamicin administration caused a severe nephrotoxicity which was evidenced by an elevated renal somatic index (RSI), serum creatinine, blood urea nitrogen, serum lactate dehydrogenase, and protein in urine with a concomitant reduction in serum albumin and normalized creatinine clearance value as compared with the controls. Moreover, a significant increase in renal contents of malondialdehyde, myeloperoxidase, and tumor necrosis factor-alpha with a significant decrease in renal reduced glutathione and superoxide dismutase activities was detected upon gentamicin administration together with increasing the sensitivity of isolated urinary bladder rings to ACh. Exposure to gentamicin induced necrosis of renal tubular epithelial cells. Flavocoxid protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by gentamicin treatment. In addition, flavocoxid significantly reduced the responses of isolated bladder rings to ACh. The results from our study indicate that flavocoxid supplement attenuates gentamicin-induced renal injury via the amelioration of

  9. Signature of seismic wave attenuation during fracture network formation

    NASA Astrophysics Data System (ADS)

    Barnhoorn, Auke; Zhubayev, Alimzhan; Houben, Maartje; Hardebol, Nico; Smeulders, David

    2015-04-01

    Seismic waves are significantly affected by the presence of fractures and faults. Fractures alter the arrival time of a seismic wave and the amplitude of the seismic wave. Attenuation of a seismic wave is the reduction of wave amplitude due to the presence of e.g. fractures. Attenuation of acoustic compressional P- and shear S-waves have been measured in laboratory studies on different rock types. These studies generally show a decrease in attenuation with an increase in stress. This decrease in attenuation is attributed to progressive crack closure of pre-existing cracks. The stress-dependent decrease in attenuation reported in these studies all occur within the elastic deformation field, i.e. below yield stress levels and thus no additional cracks/micro-fractures have yet been formed. At stress levels just above the yield strength the first fractures start to form. With increasing stress, fractures nucleate, grow and coalesce until a connected network of fractures has developed at which failure of the rock sample occurs. The change in attenuation during the fracturing process however has seldom been investigated. In analogy to fracture closure, where attenuation generally decreases, fracture formation should cause again an increase in attenuation. Here we report an experimental study on shales from Whitby (UK), where s-wave attenuation was measured in the laboratory during an increase in stress towards fracture formation until complete failure of the shale samples. Before yield stress conditions, as expected an increase in stress caused a gradual decrease in attenuation. At the transition from elastic to inelastic deformation behaviour, the first microfractures start to form and attenuation starts to increase again. This reversal in attenuation behaviour could potentially be used as an indicator that failure of a rock mass under stress is imminent (imminence of seismicity). The measured seismic velocities do not depict the transition from elastic to inelastic

  10. Chicago sky blue 6B, a vesicular glutamate transporters inhibitor, attenuates methamphetamine-induced hyperactivity and behavioral sensitization in mice.

    PubMed

    He, Zongsheng; Yan, Lingdi; Yong, Zheng; Dong, Zhaoqi; Dong, Huajin; Gong, Zehui

    2013-02-15

    Several lines of evidence demonstrate that glutamatergic system plays an important role in drug addiction. The present study was designed to investigate the effects of Chicago sky blue 6B (CSB6B), a vesicular glutamate transporters (VGLUTs) inhibitor, on methamphetamine (METH)-induced behaviors in mice. Mice were induced behavioral sensitization to METH by subcutaneous injection of 1mg/kg METH once daily for 7 days and then challenged with 1mg/kg METH in 14th day. Intracerebroventricular administration of CSB6B (7.5μg) 2.5h prior to METH was to observe its effects on METH -induced behavioral sensitization. Our results showed that the expressions of behavioral sensitization were significantly attenuated by intracerebroventricular administration of CSB6B 2.5h prior to METH either during the development period or before methamphetamine challenge in mice, while CSB6B itself had no effect on locomotor activity. Meanwhile, pretreatment of CSB6B also attenuated hyperactivity caused by a single injection of METH in mice. These results demonstrated that CSB6B, a VGLUTs inhibitor, attenuated acute METH-induced hyperactivity and chronic METH-induced behavioral sensitization, which indicated that VGLUTs were involved in the effect of chronic METH-induced behavioral sensitization and may be a new target against the addiction of METH.

  11. Cuprizone and piperonyl butoxide, proposed inhibitors of T-cell function, attenuate experimental allergic encephalomyelitis in SJL mice.

    PubMed

    Emerson, M R; Biswas, S; LeVine, S M

    2001-10-01

    Multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE), are autoimmune demyelinating diseases with autoreactive T-cells acting as important mediators of pathogenesis. Cuprizone, a copper chelator, and piperonyl butoxide (PBO), a pesticide synergist, are implicated to inhibit T-cell activation and function. The purpose of this study was to assess whether either of these agents would suppress PLP-peptide-induced EAE in the SJL mouse. Indeed, treatment with cuprizone beginning 1 week prior to disease induction, and PBO administration from days 1 to 9 of EAE, significantly attenuated EAE clinical severity. Furthermore, both agents decreased blood CD4+/CD8+ ratios, and reduced signs of chronic graft vs. host disease (GVHD) indicating attenuation of an immune T-cell response. These results suggest that cuprizone and PBO suppress EAE and use of these agents will provide insights into the mechanisms of T-cell mediated diseases.

  12. NAD(+) administration decreases doxorubicin-induced liver damage of mice by enhancing antioxidation capacity and decreasing DNA damage.

    PubMed

    Wang, Ban; Ma, Yingxin; Kong, Xiaoni; Ding, Xianting; Gu, Hongchen; Chu, Tianqing; Ying, Weihai

    2014-04-05

    One of the major obstacles for cancer treatment is the toxic side effects of anti-cancer drugs. Doxorubicin (DOX) is one of the most widely used anti-cancer drugs, which produces significant toxic side effects on the heart and such organs as the liver. Because NAD(+) can decrease cellular or tissue damage under multiple conditions, we hypothesized that NAD(+) administration may decrease DOX-induced hepatotoxicity. In this study we tested this hypothesis by using a mouse model, showing that NAD(+) administration can significantly attenuate DOX-induced increase in serum glutamate oxaloacetate transaminase activity and decrease in liver weight. The NAD(+) administration also attenuated the DOX-induced increases in the levels of double-strand DNA (dsDNA) damage, TUNEL signals, and active caspase-3. Furthermore, our data has suggested that the NAD(+) administration could produce protective effects at least partially by restoring the antioxidation capacity of the liver, because NAD(+) administration can attenuate the decreases in both the GSH levels and the glutathione reductase activity of the DOX-treated liver, which could play a significant role in the DOX-induced hepatotoxicity. This finding has provided the first evidence indicating that NAD(+) is capable of increasing the antioxidation capacity of tissues. Collectively, our study has found that NAD(+) can significantly decrease DOX-induced liver damage at least partially by enhancing antioxidation capacity and decreasing dsDNA damage. Because it can also selectively decrease tumor cell survival, NAD(+) may have significant merits over antioxidants for applying jointly with DOX to decrease the toxic side effects of DOX.

  13. Attenuation of thermal nociception and hyperalgesia by VR1 blockers

    PubMed Central

    García-Martínez, Carolina; Humet, Marc; Planells-Cases, Rosa; Gomis, Ana; Caprini, Marco; Viana, Felix; De la Peña, Elvira; Sanchez-Baeza, Francisco; Carbonell, Teresa; De Felipe, Carmen; Pérez-Payá, Enrique; Belmonte, Carlos; Messeguer, Angel; Ferrer-Montiel, Antonio

    2002-01-01

    Vanilloid receptor subunit 1 (VR1) appears to play a critical role in the transduction of noxious chemical and thermal stimuli by sensory nerve endings in peripheral tissues. Thus, VR1 antagonists are useful compounds to unravel the contribution of this receptor to pain perception, as well as to induce analgesia. We have used a combinatorial approach to identify new, nonpeptidic channel blockers of VR1. Screening of a library of trimers of N-alkylglycines resulted in the identification of two molecules referred to as DD161515 {N-[2-(2-(N-methylpyrrolidinyl)ethyl]glycyl]-[N-[2,4-dichlorophenethyl]glycyl]-N-(2,4-dichlorophenethyl)glycinamide} and DD191515 {[N-[3-(N,N-diethylamino)propyl]glycyl]-[N-[2,4-dichlorophenethyl]glycyl]-N-(2,4-dichlorophenethyl)glycinamide} that selectively block VR1 channel activity with micromolar efficacy, rivaling that characteristic of vanilloid-related inhibitors. These compounds appear to be noncompetitive VR1 antagonists that recognize a receptor site distinct from that of capsaicin. Intraperitoneal administration of both trialkylglycines into mice significantly attenuated thermal nociception as measured in the hot plate test. It is noteworthy that these compounds eliminated pain and neurogenic inflammation evoked by intradermal injection of capsaicin into the animal hindpaw, as well as the thermal hyperalgesia induced by tissue irritation with nitrogen mustard. In contrast, responses to mechanical stimuli were not modified by either compound. Modulation of sensory nerve fibers excitability appears to underlie the peptoid analgesic activity. Collectively, these results indicate that blockade of VR1 activity attenuates chemical and thermal nociception and hyperalgesia, supporting the tenet that this ionotropic receptor contributes to chemical and thermal sensitivity and pain perception in vivo. These trialkylglycine-based, noncompetitive VR1 antagonists may likely be developed into analgesics to treat inflammatory pain. PMID:11854530

  14. Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia.

    PubMed

    Bart, Nicole K; Curtis, M Kate; Cheng, Hung-Yuan; Hungerford, Sara L; McLaren, Ross; Petousi, Nayia; Dorrington, Keith L; Robbins, Peter A

    2016-08-01

    Sustained hypoxia over several hours induces a progressive rise in pulmonary artery systolic pressure (PASP). Administration of intravenous iron immediately prior to the hypoxia exposure abrogates this effect, suggesting that manipulation of iron stores may modify hypoxia-induced pulmonary hypertension. Iron (ferric carboxymaltose) administered intravenously has a plasma half-life of 7-12 h. Thus any therapeutic use of intravenous iron would require its effect on PASP to persist long after the iron-sugar complex has been cleared from the blood. To examine this, we studied PASP during sustained (6 h) hypoxia on 4 separate days (days 0, 1, 8, and 43) in 22 participants. On day 0, the rise in PASP with hypoxia was well matched between the iron and saline groups. On day 1, each participant received either 1 g of ferric carboxymaltose or saline in a double-blind manner. After administration of intravenous iron, the rise in PASP with hypoxia was attenuated by ∼50%, and this response remained suppressed on both days 8 and 43 (P < 0.001). Following administration of intravenous iron, values for ferritin concentration, transferrin saturation, and hepcidin concentration rose significantly (P < 0.001, P < 0.005, and P < 0.001, respectively), and values for transferrin concentration fell significantly (P < 0.001). These changes remained significant at day 43 We conclude that the attenuation of the pulmonary vascular response to hypoxia by elevation of iron stores persists long after the artificial iron-sugar complex has been eliminated from the blood. The persistence of this effect suggests that intravenous iron may be of benefit in some forms of pulmonary hypertension.

  15. A Change of Administration: A Significant Organizational Life Event.

    ERIC Educational Resources Information Center

    Stine, Deborah E.

    The case study presented in this paper illustrates how the succession process for principals is similar to that described by Gabarro in his study of corporate succession. Leader succession involves five major stages: (1) taking hold; (2) immersion; (3) reshaping; (4) consolidation; and (5) refinement. Success most frequently occurs in conjunction…

  16. Striatal malonate lesions are attenuated in neuronal nitric oxide synthase knockout mice.

    PubMed

    Schulz, J B; Huang, P L; Matthews, R T; Passov, D; Fishman, M C; Beal, M F

    1996-07-01

    Intrastriatal administration of the reversible succinate dehydrogenase inhibitor malonate produces both energy depletion and striatal lesions by a secondary excitotoxic mechanism. To investigate the role of nitric oxide (NO.) in the pathogenesis of the lesions we examined malonate toxicity in mice in which the genes for neuronal nitric oxide synthase (nNOS) or endothelial nitric oxide synthase (eNOS) were disrupted. Malonate striatal lesions were significantly attenuated in the nNOS mutant mice, and they were significantly increased in the eNOS mutant mice. Malonate-induced increases in levels of 2,3- and 2,5-dihydroxybenzoic acid/salicylate, markers of hydroxyl radical generation, were significantly attenuated in the nNOS knockout mice. Malonate-induced increases in 3-nitrotyrosine, a marker for peroxynitrite-mediated damage, were blocked in the nNOS mice, whereas a significant increase occurred in the eNOS mice. These findings show that NO. produced by nNOS results in generation of peroxynitrite, which plays a role in malonate neurotoxicity.

  17. The new approach of polarimetric attenuation correction for improving radar quantitative precipitation estimation(QPE)

    NASA Astrophysics Data System (ADS)

    Gu, Ji-Young; Suk, Mi-Kyung; Nam, Kyung-Yeub; Ko, Jeong-Seok; Ryzhkov, Alexander

    2016-04-01

    To obtain high-quality radar quantitative precipitation estimation data, reliable radar calibration and efficient attenuation correction are very important. Because microwave radiation at shorter wavelength experiences strong attenuation in precipitation, accounting for this attenuation is the essential work at shorter wavelength radar. In this study, the performance of different attenuation/differential attenuation correction schemes at C band is tested for two strong rain events which occurred in central Oklahoma. And also, a new attenuation correction scheme (combination of self-consistency and hot-spot concept methodology) that separates relative contributions of strong convective cells and the rest of the storm to the path-integrated total and differential attenuation is among the algorithms explored. A quantitative use of weather radar measurement such as rainfall estimation relies on the reliable attenuation correction. We examined the impact of attenuation correction on estimates of rainfall in heavy rain events by using cross-checking with S-band radar measurements which are much less affected by attenuation and compared the storm rain totals obtained from the corrected Z and KDP and rain gages in these cases. This new approach can be utilized at shorter wavelength radars efficiently. Therefore, it is very useful to Weather Radar Center of Korea Meteorological Administration preparing X-band research dual Pol radar network.

  18. Tree attenuation at 20 GHz: Foliage effects

    NASA Technical Reports Server (NTRS)

    Vogel, Wolfhard J.; Goldhirsh, Julius

    1993-01-01

    Static tree attenuation measurements at 20 GHz (K-Band) on a 30 deg slant path through a mature Pecan tree with and without leaves showed median fades exceeding approximately 23 dB and 7 dB, respectively. The corresponding 1% probability fades were 43 dB and 25 dB. Previous 1.6 GHz (L-Band) measurements for the bare tree case showed fades larger than those at K-Band by 3.4 dB for the median and smaller by approximately 7 dB at the 1% probability. While the presence of foliage had only a small effect on fading at L-Band (approximately 1 dB additional for the median to 1% probability range), the attenuation increase was significant at K-Band, where it increased by about 17 dB over the same probability range.

  19. Tree attenuation at 20 GHz: Foliage effects

    NASA Astrophysics Data System (ADS)

    Vogel, Wolfhard J.; Goldhirsh, Julius

    1993-08-01

    Static tree attenuation measurements at 20 GHz (K-Band) on a 30 deg slant path through a mature Pecan tree with and without leaves showed median fades exceeding approximately 23 dB and 7 dB, respectively. The corresponding 1% probability fades were 43 dB and 25 dB. Previous 1.6 GHz (L-Band) measurements for the bare tree case showed fades larger than those at K-Band by 3.4 dB for the median and smaller by approximately 7 dB at the 1% probability. While the presence of foliage had only a small effect on fading at L-Band (approximately 1 dB additional for the median to 1% probability range), the attenuation increase was significant at K-Band, where it increased by about 17 dB over the same probability range.

  20. Rutaecarpine attenuates hypoxia-induced right ventricular remodeling in rats.

    PubMed

    Li, Wen-Qun; Li, Xiao-Hui; Du, Jie; Zhang, Wang; Li, Dai; Xiong, Xiao-Ming; Li, Yuan-Jian

    2016-07-01

    Rutaecarpine has been shown to exhibit wide pharmacological effects in the cardiovascular system via stimulation of calcitonin gene-related peptide (CGRP) release. In the present study, the effect of rutaecarpine on hypoxia-induced right ventricular (RV) remodeling and the underlying mechanisms were evaluated. RV remodeling was induced by hypoxia (10 % O2, 3 weeks) in rats. Rats were treated with rutaecarpine (20 or 40 mg/kg) by intragastric administration. Proliferation of cardiac fibroblasts was induced by TGF-β1 (5 ng/mL) and determined by MTS and EdU incorporation method. Cardiac fibroblasts were treated with exogenous CGRP (10 or 100 nM). The concentrations of CGRP and TGF-β1 in plasma were measured by ELISA. The expression of eIF3a, p27, α-SMA, collagen-I/III, ANP, and BNP were measured by real-time PCR or western blot. Hypoxia induced an increase of right ventricle systolic pressure (RVSP), ration of RV/LV+S, and RV/tibial length in rats, while cardiac hypertrophy, apoptosis, and fibrosis were detected. The expression of ANP, BNP, α-SMA, collagen-I, collagen-III, eIF3a, and TGF-β1 was up-regulated, and the expression of p27 was down-regulated in the right ventricle of hypoxia-treated rats. The plasma concentration of CGRP was decreased and TGF-β1 was increased in hypoxia-treated rats. All of these effects induced by hypoxia were attenuated by rutaecarpine in a dose-dependent manner. In cultured cardiac fibroblasts, TGF-β1 significantly promoted the proliferation and up-regulated the expression of α-SMA and collagen-I/III, while the expression of eIF3a was up-regulated and the expression of p27 was down-regulated. The effects of TGF-β1 were attenuated by CGRP. CGRP8-37, a selective CGRP receptor antagonist, abolished the effects of CGRP. Rutaecarpine attenuates hypoxia-induced RV remodeling via stimulation of CGRP release, and the effects of rutaecarpine involve the eIF3a/p27 pathway.

  1. Bubbles attenuate elastic waves at seismic frequencies

    NASA Astrophysics Data System (ADS)

    Tisato, Nicola; Quintal, Beatriz; Chapman, Samuel; Podladchikov, Yury; Burg, Jean-Pierre

    2016-04-01

    The vertical migration of multiphase fluids in the crust can cause hazardous events such as eruptions, explosions, pollution and earthquakes. Although seismic tomography could potentially provide a detailed image of such fluid-saturated regions, the interpretation of the tomographic signals is often controversial and fails in providing a conclusive map of the subsurface saturation. Seismic tomography should be improved considering seismic wave attenuation (1/Q) and the dispersive elastic moduli which allow accounting for the energy lost by the propagating elastic wave. In particular, in saturated media a significant portion of the energy carried by the propagating wave is dissipated by the wave-induced-fluid-flow and the wave-induced-gas-exsolution-dissolution (WIGED) mechanisms. The WIGED mechanism describes how a propagating wave modifies the thermodynamic equillibrium between different fluid phases causing the exsolution and the dissolution of the gas in the liquid, which in turn causes a significant frequency dependent 1/Q and moduli dispersion. The WIGED theory was initially postulated for bubbly magmas but only recently was extended to bubbly water and experimentally demonstrated. Here we report these theory and laboratory experiments. Specifically, we present i) attenuation measurements performed by means of the Broad Band Attenuation Vessel on porous media saturated with water and different gases, and ii) numerical experiments validating the laboratory observations. Finally, we will extend the theory to fluids and to pressure-temperature conditions which are typical of phreatomagmatic and hydrocarbon domains and we will compare the propagation of seismic waves in bubble-free and bubble-bearing subsurface domains. With the present contribution we extend the knowledge about attenuation in rocks which are saturated with multiphase fluid demonstrating that the WIGED mechanism could be extremely important to image subsurface gas plumes.

  2. A two-component rain model for the prediction of attenuation statistics

    NASA Technical Reports Server (NTRS)

    Crane, R. K.

    1982-01-01

    A two-component rain model has been developed for calculating attenuation statistics. In contrast to most other attenuation prediction models, the two-component model calculates the occurrence probability for volume cells or debris attenuation events. The model performed significantly better than the International Radio Consultative Committee model when used for predictions on earth-satellite paths. It is expected that the model will have applications in modeling the joint statistics required for space diversity system design, the statistics of interference due to rain scatter at attenuating frequencies, and the duration statistics for attenuation events.

  3. METHAMPHETAMINE SELF-ADMINISTRATION IN HUMANS DURING D-AMPHETAMINE MAINTENANCE

    PubMed Central

    Pike, Erika; Stoops, William W.; Hays, Lon R.; Glaser, Paul E. A.; Rush, Craig R.

    2014-01-01

    Agonist replacement may be a viable treatment approach for managing stimulant use disorders. This study sought to determine the effects of d-amphetamine maintenance on methamphetamine self-administration in stimulant using human participants. We predicted d-amphetamine maintenance would reduce methamphetamine self-administration. Eight participants completed the protocol, which tested two d-amphetamine maintenance conditions in counter-balanced order (0 and 40 mg/day). Participants completed 4 experimental sessions under each maintenance condition in which they first sampled one of four doses of intranasal methamphetamine (0, 10, 20, or 30 mg). Participants then had the opportunity to respond on a computerized progressive ratio task to earn portions of the sampled methamphetamine dose. Subject-rated drug-effect and physiological measures were completed at regular intervals prior to and after sampling methamphetamine. Methamphetamine was self-administered as an orderly function of dose regardless of the maintenance condition. Methamphetamine produced prototypical subject-rated effects on 13 items of the drug-effects questionnaires, 10 of which were attenuated by d-amphetamine maintenance (e.g., increased ratings were attenuated on items such as Any Effect, Like Drug, and Willing to Take Again on the Drug Effect Questionnaire). Methamphetamine produced significant increases in systolic blood pressure, which were attenuated by d-amphetamine maintenance compared to placebo maintenance. Methamphetamine was well tolerated during d-amphetamine maintenance and no adverse events occurred. Although d-amphetamine attenuated some subject-rated effects of methamphetamine, the self-administration results are concordant with those of clinical trials showing that d-amphetamine did not reduce methamphetamine use. Unique pharmacological approaches may be needed for treating amphetamine use disorders. PMID:25154010

  4. Thioacetamide-induced Hepatocellular Necrosis Is Attenuated in Diet-induced Obese Mice

    PubMed Central

    Shirai, Makoto; Arakawa, Shingo; Miida, Hiroaki; Matsuyama, Takuya; Kinoshita, Junzo; Makino, Toshihiko; Kai, Kiyonori; Teranishi, Munehiro

    2013-01-01

    To assess modification of thioacetamide-induced hepatotoxicity in mice fed a high-fat diet, male C57BL/6J mice were fed a normal rodent diet or a high-fat diet for 8 weeks and then treated once intraperitoneally with thioacetamide at 50 mg/kg body weight. At 24 and 48 hours after administration, massive centrilobular hepatocellular necrosis was observed in mice fed the normal rodent diet, while the necrosis was less severe in mice fed the high-fat diet. In contrast, severe swelling of hepatocytes was observed in mice fed the high-fat diet. In addition, mice fed the high-fat diet displayed more than a 4-fold higher number of BrdU-positive hepatocytes compared with mice fed the normal rodent diet at 48 hours after thioacetamide treatment. To clarify the mechanisms by which the hepatic necrosis was attenuated, we investigated exposure to thioacetamide and one of its metabolites, the expression of CYP2E1, which converts thioacetamide to reactive metabolites, and the content of glutathione S-transferases in the liver. However, the reduced hepatocellular necrosis noted in mice fed the high-fat diet could not be explained by the differences in exposure to thioacetamide or thioacetamide sulfoxide or by differences in the expression of drug-metabolizing enzymes. On the other hand, at 8 hours after thioacetamide administration, hepatic total glutathione in mice fed the high-fat diet was significantly lower than that in mice fed the normal diet. Hence, decreased hepatic glutathione amount is a candidate for the mechanism of the attenuated necrosis. In conclusion, this study revealed that thioacetamide-induced hepatic necrosis was attenuated in mice fed the high-fat diet. PMID:23914059

  5. Different profiles of quercetin metabolites in rat plasma: comparison of two administration methods.

    PubMed

    Kawai, Yoshichika; Saito, Satomi; Nishikawa, Tomomi; Ishisaka, Akari; Murota, Kaeko; Terao, Junji

    2009-03-23

    The bioavailability of polyphenols in human and rodents has been discussed regarding their biological activity. We found different metabolite profiles of quercetin in rat plasma between two administration procedures. A single intragastric administration (50 mg/kg) resulted in the appearance of a variety of metabolites in the plasma, whereas only a major fraction was detected by free access (1% quercetin). The methylated/non-methylated metabolites ratio was much higher in the free access group. Mass spectrometric analyses showed that the fraction from free access contained highly conjugated quercetin metabolites such as sulfo-glucuronides of quercetin and methylquercetin. The metabolite profile of human plasma after an intake of onion was similar to that with intragastric administration in rats. In vitro oxidation of human low-density lipoprotein showed that methylation of the catechol moiety of quercetin significantly attenuated the antioxidative activity. These results might provide information about the bioavailability of quercetin when conducting animal experiments.

  6. Effects of vasopressin administration on diuresis of water immersion in normal humans

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Denunzio, A. G.; Loutzenhiser, R. D.

    1981-01-01

    The influence of vasopressin suppression on the diuresis encountered during water immersion is investigated in studies on normal humans immersed to the neck. Six hydrated male subjects were studied on two occasions while undergoing 6 h of immersion without or during the administration of aqueous vasopressin for the initial 4 h. Neck immersion is found to result in a significant increase in urinary flow rate beginning in the first hour and persisting throughout the immersion. The administration of vasopressin markedly attenuated the diuretic response throughout the period of infusion, while cessation of vasopressin administration during the final 2 h of immersion resulted in a marked offset of the antidiuresis. Results thus support the view that the suppression of antidiuretic hormone contributes to the immersion diuresis of hydrated subjects.

  7. Effects of taurine administration on exercise.

    PubMed

    Yatabe, Yoshihisa; Miyakawa, Shumpei; Ohmori, Hajime; Mishima, Hajime; Adachi, Takako

    2009-01-01

    Taurine concentration in rat skeletal muscles after endurance running, with and without taurine administration was studied. Taurine concentrations in skeletal muscles was significantly decreased in exercised groups without taurine administration. However, taurine administration reduced the decrease of taurine concentration in skeletal muscles in exercise. Oral administration of taurine has effect for maintaining taurine concentration in skeletal muscles in exercise. The duration of running time to exhaustion of rats, with and without taurine administration were studied. The duration of running time to exhaustion was significantly increased by taurine administration. Oral administration of taurine increases the ability of physical endurance. Rat urinary excretions of creatinine, creatine, 3-methylhistidine (3-MH) after treadmill running, with and without taurine administration were studied. Rat urinary excretions of creatinine, creatine, 3-MH after treadmill running was significantly decreased with taurine administration. Taurine administration was considered to reduce the exercise-induced muscle fatigue.

  8. Carnosine Reduces Oxidative Stress and Reverses Attenuation of Righting and Postural Reflexes in Rats with Thioacetamide-Induced Liver Failure.

    PubMed

    Milewski, Krzysztof; Hilgier, Wojciech; Fręśko, Inez; Polowy, Rafał; Podsiadłowska, Anna; Zołocińska, Ewa; Grymanowska, Aneta W; Filipkowski, Robert K; Albrecht, Jan; Zielińska, Magdalena

    2016-02-01

    Cerebral oxidative stress (OS) contributes to the pathogenesis of hepatic encephalopathy (HE). Existing evidence suggests that systemic administration of L-histidine (His) attenuates OS in brain of HE animal models, but the underlying mechanism is complex and not sufficiently understood. Here we tested the hypothesis that dipeptide carnosine (β-alanyl-L-histidine, Car) may be neuroprotective in thioacetamide (TAA)-induced liver failure in rats and that, being His metabolite, may mediate the well documented anti-OS activity of His. Amino acids [His or Car (100 mg/kg)] were administrated 2 h before TAA (i.p., 300 mg/kg 3× in 24 h intervals) injection into Sprague-Dawley rats. The animals were thus tested for: (i) brain prefrontal cortex and blood contents of Car and His, (ii) amount of reactive oxygen species (ROS), total antioxidant capacity (TAC), GSSG/GSH ratio and thioredoxin reductase (TRx) activity, and (iii) behavioral changes (several models were used, i.e. tests for reflexes, open field, grip test, Rotarod). Brain level of Car was reduced in TAA rats, and His administration significantly elevated Car levels in control and TAA rats. Car partly attenuated TAA-induced ROS production and reduced GSH/GSSG ratio, whereas the increase of TRx activity in TAA brain was not significantly modulated by Car. Further, Car improved TAA-affected behavioral functions in rats, as was shown by the tests of righting and postural reflexes. Collectively, the results support the hypothesis that (i) Car may be added to the list of neuroprotective compounds of therapeutic potential on HE and that (ii) Car mediates at least a portion of the OS-attenuating activity of His in the setting of TAA-induced liver failure.

  9. Rain attenuation statistics over millimeter wave bands in South Korea

    NASA Astrophysics Data System (ADS)

    Shrestha, Sujan; Choi, Dong-You

    2017-01-01

    Rain induced degradations are significant for terrestrial microwave links operating at frequencies higher than 10 GHz. Paper presents analyses done on rain attenuation and rainfall data for three years between 2013 till 2015, in 3.2 km experimental link of 38 GHz and 0.1 km link at 75 GHz. The less link distance is maintained for 75 GHz operating frequency in order to have better recording of propagation effect as such attenuation induced by rain. OTT Parsivel is used for collection of rain rate database which show rain rate of about 50 mm/h and attenuation values of 20.89 and 28.55 dB are obtained at 0.01% of the time for vertical polarization under 38 and 75 GHz respectively. Prediction models, namely, ITU-R P. 530-16, Da Silva Mello, Moupfouma, Abdulrahman, Lin and differential equation approach are analyzed. This studies help to identify most suitable rain attenuation model for higher microwave bands. While applying ITU-R P. 530-16, the relative error margin of about 3%, 38% and 42% along with 80, 70, 61% were obtained in 0.1%, 0.01% and 0.001% of the time for vertical polarization under 38 and 75 GHz respectively. Interestingly, ITU-R P. 530-16 shows relatively closer estimation to measured rain attenuation at 75 GHz with relatively less error probabilities and additionally, Abdulrahman and ITU-R P. 530-16 results in better estimation to the measured rain attenuation at 38 GHz link. The performance of prominent rain attenuation models are judged with different error matrices as recommended by ITU-R P. 311-15. Furthermore, the efficacy of frequency scaling technique of rain attenuation between links distribution are also discussed. This study shall be useful for making good considerations in rain attenuation predictions for terrestrial link operating at higher frequencies.

  10. Attenuation of paraquat-induced motor behavior and neurochemical disturbances by L-valine in vivo.

    PubMed

    Chanyachukul, Thida; Yoovathaworn, Krongtong; Thongsaard, Watchareewan; Chongthammakun, Sukumal; Navasumrit, Panida; Satayavivad, Jutamaad

    2004-05-02

    Alterations of motor behavioral patterns and monoamine contents in the discrete rat brain areas after acute paraquat exposure (3, 5, 10, 20 mg/kg, s.c.) have been studied. The results showed that paraquat at the doses of 5, 10, and 20 mg/kg significantly reduced locomotive, stereotypic, and rotational behaviors. Significant decreases of norepinephrine (NE) contents in cortex and hypothalamus, as well as striatal contents of dopamine (DA) and its acidic metabolites, were detected. In addition, L-valine (200 mg/kg, i.p.) significantly attenuated paraquat-induced toxicity at moderate dose (5 mg/kg) but not at high dose (20 mg/kg). The results provide evidence that paraquat can enter the brain as illustrated by the alterations in the motor behavioral pattern and neurochemical contents. Furthermore, the attenuation effect of L-valine against systemic administration of paraquat-induced motor behaviors was detected, with a slightly protective effect on paraquat-induced neurochemical alterations.

  11. Yulangsan polysaccharide attenuates withdrawal symptoms and regulates the NO pathway in morphine-dependent rats.

    PubMed

    Chen, Chunxia; Nong, Zhihuan; Huang, Jiangchun; Chen, Zhaoni; Zhang, Shijun; Jiao, Yang; Chen, Xiaoyu; Huang, Renbin

    2014-06-06

    Yulangsan polysaccharide (YLSP) has been utilized as a phytomedicine to managing nervous dysfunction in China. Thus, this study aimed to evaluate the potential YLSP-mediated detoxification role against morphine dependence in rats. The results indicated that the morphine dependence model significantly increased withdrawal symptoms, levels of NO and NOS (P<0.05). Furthermore, monoaminergic neurotransmitters, including DA and NE, were detected at elevated levels in the ventral tegmental area (VTA), hippocampus (HIP) and prefrontal cortex (PFC), respectively, while the level of DA was decreased and NE was increased in the nucleus accumbens (NAc). Conversely, YLSP administration significantly reversed naloxone-induced withdrawal symptoms, expression of brain NO and NOS, and monoaminergic neurotransmitters (P<0.05). Interestingly, YLSP shows an even more effective trend in attenuating withdrawal symptoms than does clonidine, although without a significant difference. These findings indicate that YLSP attenuation of the naloxone-induced withdrawal symptoms of morphine dependence may be mediated by regulation of the NO pathway and modulation of monoaminergic neurotransmitters.

  12. Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson's Disease

    PubMed Central

    Wang, Bing; Chen, Li-Hua

    2016-01-01

    In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE) precursor droxidopa (L-DOPS) or α2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA) or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain. PMID:27747105

  13. Resveratrol Attenuates Diabetic Nephropathy via Modulating Angiogenesis

    PubMed Central

    Zhang, Min; Zhang, Liying; Chen, Jing; Gu, Yong; Hao, Chuan-Ming

    2013-01-01

    Angiogenesis plays an important role in the pathogenesis of diabetic nephropathy (DN). In the present study, we investigated the therapeutic potential of resveratrol, a polyphenol with antiangiogenic activity in DN. In a type 1 diabetic rat model, resveratrol treatment blunted the increases of urine albumin excretion, kidney weight and creatinine clearance rate. The increases of glomerular diameter, mesangium accumulation, glomerular basement membrane thickness and renal fibrosis in diabetic rats were also reduced by resveratrol treatment. In the diabetic kidney, increased expression of vascular endothelial growth factor (VEGF), Flk-1 and angiopoietin 2, and reduced expression of Tie-2 were observed. These changes in angiogenic hormones and associated receptors were attenuated by resveratrol treatment. No changes in angiopoietin 1 expression were detected among each group of rats. Resveratrol also significantly downregulated high glucose-induced VEGF and Flk-1 expressions in cultured mouse glomerular podocytes and endothelial cells, respectively. These effects were attenuated by knocking-down silent information regulator 1 (Sirt1) expression. In contrast, upregulation of Sirt1 in cultured endothelial cells reduced Flk-1 expression. Increased permeability and cellular junction disruption of cultured endothelial cells caused by VEGF were also inhibited by resveratrol pretreatment. Taken together, the present study demonstrated that resveratrol may attenuate DN via modulating angiogenesis. PMID:24312656

  14. Practitioner perceptions of attenuated psychosis syndrome.

    PubMed

    Jacobs, Elizabeth; Kline, Emily; Schiffman, Jason

    2011-09-01

    The "Attenuated Psychosis Syndrome" (APS, sometimes referred to as the "schizophrenia prodrome") is characterized by subthreshold psychotic-like symptoms and functional decline, and is often associated with significant disability. These symptoms may cause impairment and are of further interest due to their predictive relation to schizophrenia and other psychotic disorders. These symptoms currently are not represented in the diagnostic system for mental health, and it is unclear how they are conceptualized by relevant professionals. The current study surveyed a national sample (n=303) of clinical psychologists, psychiatrists, and general practitioners regarding their clinical appraisal of APS. Practitioners were asked to respond to vignettes representing three conditions: psychosis, subthreshold psychosis (indicating 'attenuated' psychosis symptoms), and no psychotic symptoms. Practitioners' responses suggested that APS is viewed consistently with a DSM-IV-TR defined mental disorder and that most clinicians may diagnose this condition as a full threshold psychotic disorder. Findings tentatively suggest that the inclusion of an attenuated psychosis symptoms category in the forthcoming DSM-5 may be helpful in improving diagnostic reliability and facilitating best practice among community practitioners.

  15. Bubbles cause seismic wave attenuation: Laboratory measurements and numerical simulations

    NASA Astrophysics Data System (ADS)

    Tisato, Nicola; Quintal, Beatriz; Chapman, Samuel; Podladchikov, Yury; Grasselli, Giovanni; Burg, Jean-Pierre

    2015-04-01

    Seismic wave attenuation (1/Q) is a key to uncover the saturation and, in general, to improve the monitoring and surveying of subsurface domains. Nevertheless, how fluids that saturate rocks absorb elastic energy (i.e. cause 1/Q) is still poorly understood, studied and incorporated in geophysical methods. One of the invoked mechanisms, wave induced fluid flow (WIFF), is reputed to cause significant attenuation. This mechanism is governed by the flow of viscous fluids into a porous rock, and causes attenuation as a function of the fluid diffusivity [m2/s] and the pressure gradient [Pa/m], which is generated by the propagation of the elastic wave. However, some published, and newly acquired laboratory data-sets reporting 1/Q in almost fully saturated sandstones are difficult to explain with WIFF theories as they are frequency-dependent and have maximum of attenuation at frequencies

  16. Preservation of endothelium-dependent relaxation in cholesterol-fed and streptozotocin-induced diabetic mice by the chronic administration of cholestyramine.

    PubMed Central

    Kamata, K.; Sugiura, M.; Kojima, S.; Kasuya, Y.

    1996-01-01

    1. Experiments were designed to investigate the effects of the low density lipoprotein (LDL)-lowering drugs cholestyramine on serum LDL levels and endothelium-dependent relaxation to acetylcholine (ACh) in cholesterol-fed or streptozotocin (STZ)-induced diabetic mice. 2. In aortic rings from control mice, ACh or A23187 caused concentration-dependent relaxation. The relaxations caused by ACh or A23187 were significantly attenuated in aortic rings from cholesterol-fed and STZ-diabetic mice. The attenuated vasodilatation in both cholesterol-fed and diabetic mice was returned to normal by chronic administration of cholestyramine. The endothelium-independent relaxations of aortic rings induced by sodium nitroprusside (SNP) were not significantly different between control, cholesterol-fed and STZ-induced diabetic mice. 3. The increased LDL levels in cholesterol-fed and diabetic mice were returned to normal by the chronic administration of cholestyramine. Chronic administration of cholestyramine had no effects on serum glucose levels. 4. These results suggest that attenuated endothelium-dependent vasodilatations in both cholesterol-fed and STZ-diabetic mice are improved by the chronic administration of cholestyramine, and these effects are, at least in part, due to lowering serum LDL levels. PMID:8735642

  17. Ultrasound attenuation in normal and spontaneously degenerated articular cartilage.

    PubMed

    Nieminen, Heikki J; Saarakkala, Simo; Laasanen, Mikko S; Hirvonen, Jani; Jurvelin, Jukka S; Töyräs, Juha

    2004-04-01

    High-frequency ultrasound (US) measurements may provide means for the quantification of articular cartilage quality. Bovine patellar cartilage samples (n = 32) at various degenerative stages were studied using US attenuation measurements in the 5- to 9-MHz frequency range. The results were compared with the histologic, biochemical and mechanical parameters obtained for the same samples, to identify which structural or functional factors could be related to the attenuation and its variations. Attenuation, as calculated in the frequency or time domain, correlated significantly with the histologic tissue integrity (i.e., Mankin score, Spearman r = -0.576 or -0.571, p < 0.01), but the slope of attenuation vs. frequency was not related to Mankin score. Ultrasound speed was, however, the most sensitive indicator of Mankin score (r = -0.755, p < 0.01). Cartilage quality index (CQI), a combination of structural and functional parameters, correlated significantly with the attenuation or speed (r = -0.655 or -0.872, p < 0.01). Our results suggest that US attenuation and speed may be suited for the diagnostics of cartilage degeneration. (E-mail: )

  18. Targeting oxidative stress attenuates trinitrobenzene sulphonic acid induced inflammatory bowel disease like symptoms in rats: Role of quercetin

    PubMed Central

    Dodda, Dilip; Chhajed, Ruchi; Mishra, Jitendriya; Padhy, Monalisa

    2014-01-01

    Objective: This study was aimed to investigate the beneficial effects of quercetin (QCT) against trinitrobenzene sulfonic acid (TNBS) induced clinical, morphological, and biochemical alterations in rats. Materials and Methods: Colitis in rats was induced by administration of TNBS (25 mg dissolved in 0.25 ml of 30% ethanol) 8 cm into the rectum of the rat using a catheter. The animals were divided into six experimental groups (n = 6); naive (saline only without TNBS administration), control (saline + TNBS), standard (sulfasalazine 25 mg/kg + TNBS), QCT (25) (QCT 25 mg/kg + TNBS), QCT (50) (QCT 50 mg/kg + TNBS), QCT (100) (QCT 100 mg/kg + TNBS). Sulfasalazine (25 mg/kg) and QCT (25, 50 and 100 mg/kg) were administered per oral for 11 days and the colonic damage was evaluated in terms of macroscopical (body weight, stool consistency, rectal bleeding, and ulcer index) and biochemical parameters (myeloperoxidase activity, lipid peroxidation, nitrite, and glutathione). Results: Treatment with QCT (50, 100 mg/kg) for 10 days following TNBS administration significantly attenuated the clinical, morphological, and biochemical alterations induced by TNBS, whereas it was found to be not effective at its lower dose (25 mg/kg) throughout the experimental protocol. Conclusion: QCT attenuates the clinical, morphological and biochemical alterations induced by TNBS possibly via its antioxidant mechanism. PMID:24987175

  19. GABA(B) receptor agonist baclofen attenuates the development and expression of d-methamphetamine-induced place preference in rats.

    PubMed

    Li, S M; Yin, L L; Ren, Y H; Pan, L S; Zheng, J W

    2001-12-07

    The present study investigated the effect of systemic administration of the GABA(B) receptor agonist, baclofen, on the development and expression of d-methamphetamine (d-MA)-induced place preference in male Wistar rats. Using a biased and 8-day schedule of conditioning, it was found that administration of d-MA (0.5 mg/kg, i.p.) produced significant place preference. The administration of baclofen (2.5 and 5.0 mg/kg, i.p.) 30 min prior to the exposure to d-MA attenuated the development of d-MA-induced place preference (p<0.05). In addition, when it was acutely administered 30 min prior to the testing session of an already established d-MA place preference, baclofen (1.25-5.0 mg/kg, i.p.) attenuated the expression of this conditioned response in a dose-dependent manner. These results showed that baclofen suppressed the rewarding effect produced by d-MA and may be potentially effective in the treatment of methamphetamine dependence and craving.

  20. Exercise training attenuates anaphylactic venoconstriction in rat perfused liver, but does not affect anaphylactic hypotension in conscious rats.

    PubMed

    Cui, Sen; Shibamoto, Toshishige; Zhang, Wei; Kurata, Yasutaka; Kashimura, Osamu; Miyamae, Shunichi

    2010-09-01

    1. Exercise training attenuates circulatory shock due to haemorrhage, endotoxin or heatstroke. However, it remains unknown whether exercise training attenuates anaphylactic shock. Hepatic venoconstriction is involved in rat anaphylactic hypotension. In the present study, we determined the effects of exercise training on both anaphylaxis-induced segmental venoconstriction in rat perfused livers and systemic anaphylaxis in conscious rats. The role of nitric oxide (NO) in the effect of exercise on the venoconstriction of perfused livers was also examined. 2. Rats were subjected to running training on a motorized treadmill for 4 weeks. Two weeks prior to the anaphylaxis experiment, Sprague-Dawley rats were actively sensitized with the antigen ovalbumin. In isolated livers perfused portally with blood, the portal venous pressure (P(pv)) and sinusoidal pressure were measured to determine the pre- and post-sinusoidal resistances (R(pre) and R(post), respectively). In conscious rats, systemic arterial pressure (SAP) and P(pv) were determined. 3. In the perfused livers of sedentary rats, antigen administration led to a predominant presinusoidal constriction, as evidenced by 4.6- and 1.7-fold increases in R(pre) and R(post), respectively. The anaphylaxis-induced increase in R(pre) was significantly attenuated by 24% by exercise training. Inhibition of NO synthase with N(G)-nitro-L-arginine methyl ester (100 micromol/L) 10 min prior to the injection of antigen enhanced anaphylactic venoconstriction, but did not alter the effect of exercise training on the increase in R(pre). In contrast, exercise training did not attenuate either anaphylactic hypotension or portal hypertension in conscious rats. 4. In conclusion, exercise training attenuates the anaphylaxis-induced presinusoidal constriction in rat isolated perfused livers, independent of NO production. However, this action is not evident in conscious rats and exercise training does not affect anaphylactic hypotension in

  1. Triptans attenuate circadian responses to light.

    PubMed

    Basu, Priyoneel; Ie, Naomi; Wensel, Adrienne L; Baskerville, Joelle D; Smith, Victoria M; Antle, Michael C

    2015-10-01

    Daily exposure to light synchronizes the circadian clock, located in the suprachiasmatic nucleus (SCN), to external day/night cycles. These responses to light can be modified by serotonergic drugs, such as serotonin 5HT1B receptor agonists. Triptans are specific 5HT1B agonists prescribed to treat migraines. Here, we examined the effects of two triptans (zolmitriptan and sumatriptan) on photic phase resetting in Syrian hamsters. Pre-treatment with intra-SCN sumatriptan significantly attenuates, and at higher doses completely blocks, phase advances to light during the late night. Pre-treatment with systemic zolmitriptan significantly attenuates both light-induced phase advances and phase delays. Neither of these drugs, nor their vehicles, causes phase shifts on their own. Pre-treatment with zolmitriptan also significantly reduces the expression of light-induced c-fos in the SCN. Neither zolmitriptan nor vehicle alone induces significant c-fos expression in the SCN. Finally, pre-treatment with zolmitriptan does not attenuate phase shifts to intra-SCN N-methyl-d-aspartate injections, indicating that the mechanism of action for zolmitriptan is likely to be through activation of presynaptic 5HT1B receptors on retinal terminals, thereby decreasing light-induced neurotransmitter release. As triptans are commercially available medications, there is potential for their use in blocking unwanted photic phase shifting during shift-work or jet-lag. Additionally, triptans may also affect the circadian clock in patients receiving them regularly for migraines. Finally, our results may hint at the mechanism by which triptans can alleviate the photophobia that frequently accompanies migraines, namely by activating 5HT1B receptors on retinal terminals elsewhere in the brain, and thereby diminishing visually-evoked neurotransmitter signalling in those areas.

  2. Physiological and Perceptual Sensory Attenuation Have Different Underlying Neurophysiological Correlates

    PubMed Central

    Davare, Marco; Kilner, James M.

    2016-01-01

    Sensory attenuation, the top-down filtering or gating of afferent information, has been extensively studied in two fields: physiological and perceptual. Physiological sensory attenuation is represented as a decrease in the amplitude of the primary and secondary components of the somatosensory evoked potential (SEP) before and during movement. Perceptual sensory attenuation, described using the analogy of a persons' inability to tickle oneself, is a reduction in the perception of the afferent input of a self-produced tactile sensation due to the central cancellation of the reafferent signal by the efference copy of the motor command to produce the action. The fields investigating these two areas have remained isolated, so the relationship between them is unclear. The current study delivered median nerve stimulation to produce SEPs during a force-matching paradigm (used to quantify perceptual sensory attenuation) in healthy human subjects to determine whether SEP gating correlated with the behavior. Our results revealed that these two forms of attenuation have dissociable neurophysiological correlates and are likely functionally distinct, which has important implications for understanding neurological disorders in which one form of sensory attenuation but not the other is impaired. Time–frequency analyses revealed a negative correlation over sensorimotor cortex between gamma-oscillatory activity and the magnitude of perceptual sensory attenuation. This finding is consistent with the hypothesis that gamma-band power is related to prediction error and that this might underlie perceptual sensory attenuation. SIGNIFICANCE STATEMENT We demonstrate that there are two functionally and mechanistically distinct forms of sensory gating. The literature regarding somatosensory evoked potential (SEP) gating is commonly cited as a potential mechanism underlying perceptual sensory attenuation; however, the formal relationship between physiological and perceptual sensory

  3. Dexmedetomidine Attenuates Lipopolysaccharide Induced MCP-1 Expression in Primary Astrocyte

    PubMed Central

    Liu, Huan; Faez Abdelgawad, Amro

    2017-01-01

    Background. Neuroinflammation which presents as a possible mechanism of delirium is associated with MCP-1, an important proinflammatory factor which is expressed on astrocytes. It is known that dexmedetomidine (DEX) possesses potent anti-inflammatory properties. This study aimed to investigate the potential effects of DEX on the production of MCP-1 in lipopolysaccharide-stimulated astrocytes. Materials and Methods. Astrocytes were treated with LPS (10 ng/ml, 50 ng/ml, 100 ng/ml, and 1000 ng/ml), DEX (500 ng/mL), LPS (100 ng/ml), and DEX (10, 100, and 500 ng/mL) for a duration of three hours; expression levels of MCP-1 were measured by real-time PCR. The double immunofluorescence staining protocol was utilized to determine the expression of α2-adrenoceptors (α2AR) and glial fibrillary acidic protein (GFAP) on astrocytes. Results. Expressions of MCP-1 mRNA in astrocytes were induced dose-dependently by LPS. Administration of DEX significantly inhibited the expression of MCP-1 mRNA (P < 0.001). Double immunofluorescence assay showed that α2AR colocalize with GFAP, which indicates the expression of α2-adrenoceptors in astrocytes. Conclusions. DEX is a potent suppressor of MCP-1 in astrocytes induced with lipopolysaccharide through α2A-adrenergic receptors, which potentially explains its beneficial effects in the treatment of delirium by attenuating neuroinflammation. PMID:28286770

  4. Salicylic acid attenuates gentamicin-induced nephrotoxicity in rats.

    PubMed

    Randjelovic, Pavle; Veljkovic, Slavimir; Stojiljkovic, Nenad; Jankovic-Velickovic, Ljubinka; Sokolovic, Dusan; Stoiljkovic, Milan; Ilic, Ivan

    2012-01-01

    Gentamicin (GM) is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of salicylic acid (SA) in gentamicin-induced nephrotoxicity in rats. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of SA coadministration with gentamicin. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde (MDA) levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous SA administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by SA pretreatment. The results from our study indicate that SA supplement attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats.

  5. Catechin attenuates behavioral neurotoxicity induced by 6-OHDA in rats.

    PubMed

    Teixeira, M D A; Souza, C M; Menezes, A P F; Carmo, M R S; Fonteles, A A; Gurgel, J P; Lima, F A V; Viana, G S B; Andrade, G M

    2013-09-01

    This study was designed to investigate the beneficial effect of catechin in a model of Parkinson's disease. Unilateral, intrastriatal 6-hydroxydopamine (6-OHDA)-lesioned rats were pretreated with catechin (10 and 30 mg/kg) by intraperitoneal (i.p.) injection 2h before surgery and for 14 days afterwards. After treatments, apomorphine-induced rotations, locomotor activity, working memory and early and late aversive memories were evaluated. The mesencephalon was used to determine the levels of monoamines and measurement of glutathione (GSH). Immunohistochemical staining was also used to evaluate the expression of tyrosine hydroxylase (TH) in mesencephalic and striatal tissues. Catechin administration attenuated the increase in rotational behavior and the decrease in locomotor activity observed in lesioned rats. Although catechin did not rescue the impairment of late aversive memory, it protected the animals against 6-OHDA-induced working memory deficits. Furthermore, catechin treatment restored GSH levels, and significantly increased dopamine and DOPAC content, and TH-immunoreactivity in 6-OHDA-lesioned rats. Catechin protected 6-OHDA-lesioned rats due to its antioxidant action, indicating that it could be useful as an adjunctive therapy for the treatment of Parkinson's disease.

  6. Dexmedetomidine Attenuates Lipopolysaccharide Induced MCP-1 Expression in Primary Astrocyte.

    PubMed

    Liu, Huan; Davis, Jacques R J; Wu, Zhi-Lin; Faez Abdelgawad, Amro

    2017-01-01

    Background. Neuroinflammation which presents as a possible mechanism of delirium is associated with MCP-1, an important proinflammatory factor which is expressed on astrocytes. It is known that dexmedetomidine (DEX) possesses potent anti-inflammatory properties. This study aimed to investigate the potential effects of DEX on the production of MCP-1 in lipopolysaccharide-stimulated astrocytes. Materials and Methods. Astrocytes were treated with LPS (10 ng/ml, 50 ng/ml, 100 ng/ml, and 1000 ng/ml), DEX (500 ng/mL), LPS (100 ng/ml), and DEX (10, 100, and 500 ng/mL) for a duration of three hours; expression levels of MCP-1 were measured by real-time PCR. The double immunofluorescence staining protocol was utilized to determine the expression of α2-adrenoceptors (α2AR) and glial fibrillary acidic protein (GFAP) on astrocytes. Results. Expressions of MCP-1 mRNA in astrocytes were induced dose-dependently by LPS. Administration of DEX significantly inhibited the expression of MCP-1 mRNA (P < 0.001). Double immunofluorescence assay showed that α2AR colocalize with GFAP, which indicates the expression of α2-adrenoceptors in astrocytes. Conclusions. DEX is a potent suppressor of MCP-1 in astrocytes induced with lipopolysaccharide through α2A-adrenergic receptors, which potentially explains its beneficial effects in the treatment of delirium by attenuating neuroinflammation.

  7. Iron induced genotoxicity: attenuation by vitamin C and its optimization

    PubMed Central

    Parveen, Nuzhat; Ahmad, Shoeb

    2014-01-01

    Vitamin C (VC) is a well-known antioxidant and strong free radical scavenger. Its antioxidant activity is useful for protection of cellular macromolecules, particularly DNA, from oxidative damage induced by different agents. This study was undertaken to evaluate the optimum level of VC in attenuating the chromosome aberrations (CAs) and DNA damage after iron sulfate (FeSO4) acute administration in Wistar rats. The results exhibited that the increase of CAs and DNA damage induced by FeSO4, 200 mg Fe/kg, could be reduced significantly by VC pretreatment at the dose of 500 mg/kg (p<0.001), but not in the 100 mg/kg group. The findings provide evidence that VC at the dose of 500 mg/kg exerted a possible protective effect against FeSO4 induced CAs and DNA damage. The possible mechanisms of VC may be attributed to its property as a free radical scavenger or to its indirect action in reducing the level of reactive oxygen species (ROS). PMID:26109893

  8. Protective effects of branched-chain amino acids on hepatic ischemia-reperfusion-induced liver injury in rats: a direct attenuation of Kupffer cell activation.

    PubMed

    Kitagawa, Tomomi; Yokoyama, Yukihiro; Kokuryo, Toshio; Nagino, Masato

    2013-02-15

    We determined whether there is a protective effect of branched-chain amino acid (BCAA) on hepatic ischemia-reperfusion (I/R)-induced acute liver injury. Wister rats were divided into the following four groups: simple laparotomy with vehicle; simple laparotomy with BCAA (1 g/kg body wt orally); I/R (30 min clamp) with vehicle; and I/R with BCAA. Serum liver function tests and the gene expression of adhesion molecules (intercellular adhesion molecule and vascular cell adhesion molecule) and vasoconstrictor-related genes (endothelin-1) in the liver were examined. In the in vivo study, portal venous pressure, leukocyte adhesion, and hepatic microcirculation were evaluated. Furthermore, Kupffer cells were isolated and cultured with various concentrations of BCAA in the presence or absence of lipopolysaccharide (LPS). Increased levels of liver function tests following I/R were significantly attenuated by BCAA treatment. The increased expression of adhesion molecules and endothelin-1 was also significantly attenuated by BCAA treatment. Moreover, increased portal venous pressure, enhanced leukocyte adhesion, and deteriorated hepatic microcirculation following I/R were all improved by BCAA treatment. In the experiment using isolated Kupffer cells, the expression of interleukin-6, interleukin-1β, and endothelin-1 in response to LPS stimulation was attenuated by BCAA in a dose-dependent fashion. These results indicate that perioperative oral administration of BCAA has excellent therapeutic potential to reduce I/R-induced liver injury. These beneficial effects may result from the direct attenuation of Kupffer cell activation under stressful conditions.

  9. Intracerebroventricular administration of C-type natriuretic peptide suppresses food intake via activation of the melanocortin system in mice.

    PubMed

    Yamada-Goto, Nobuko; Katsuura, Goro; Ebihara, Ken; Inuzuka, Megumi; Ochi, Yukari; Yamashita, Yui; Kusakabe, Toru; Yasoda, Akihiro; Satoh-Asahara, Noriko; Ariyasu, Hiroyuki; Hosoda, Kiminori; Nakao, Kazuwa

    2013-05-01

    C-type natriuretic peptide (CNP) and its receptor are abundantly distributed in the brain, especially in the arcuate nucleus (ARC) of the hypothalamus associated with regulating energy homeostasis. To elucidate the possible involvement of CNP in energy regulation, we examined the effects of intracerebroventricular administration of CNP on food intake in mice. The intracerebroventricular administration of CNP-22 and CNP-53 significantly suppressed food intake on 4-h refeeding after 48-h fasting. Next, intracerebroventricular administration of CNP-22 and CNP-53 significantly decreased nocturnal food intake. The increment of food intake induced by neuropeptide Y and ghrelin was markedly suppressed by intracerebroventricular administration of CNP-22 and CNP-53. When SHU9119, an antagonist for melanocortin-3 and melanocortin-4 receptors, was coadministered with CNP-53, the suppressive effect of CNP-53 on refeeding after 48-h fasting was significantly attenuated by SHU9119. Immunohistochemical analysis revealed that intracerebroventricular administration of CNP-53 markedly increased the number of c-Fos-positive cells in the ARC, paraventricular nucleus, dorsomedial hypothalamus, ventromedial hypothalamic nucleus, and lateral hypothalamus. In particular, c-Fos-positive cells in the ARC after intracerebroventricular administration of CNP-53 were coexpressed with α-melanocyte-stimulating hormone immunoreactivity. These results indicated that intracerebroventricular administration of CNP induces an anorexigenic action, in part, via activation of the melanocortin system.

  10. SEISMIC ATTENUATION FOR RESERVOIR CHARACTERIZATION

    SciTech Connect

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

    2003-04-01

    In this report we will show results of seismic and well log derived attenuation attributes from a deep water Gulf of Mexico data set. This data was contributed by Burlington Resources and Seitel Inc. The data consists of ten square kilometers of 3D seismic data and three well penetrations. We have computed anomalous seismic absorption attributes on the seismic data and have computed Q from the well log curves. The results show a good correlation between the anomalous absorption (attenuation) attributes and the presence of gas as indicated by well logs.

  11. Aging attenuates the vestibulosympathetic reflex in humans

    NASA Technical Reports Server (NTRS)

    Ray, Chester A.; Monahan, Kevin D.

    2002-01-01

    BACKGROUND: The vestibular system contributes to sympathetic activation by engagement of the otolith organs. However, there is a significant loss of vestibular function with aging. Therefore, the purpose of the present study was to determine if young and older individuals differ in their cardiovascular and sympathetic responses to otolithic stimulation (ie, head-down rotation, HDR). We hypothesized that responses to otolithic stimulation would be attenuated in older adults because of morphological and physiological alterations that occur in the vestibular system with aging. METHODS AND RESULTS: Arterial blood pressure, heart rate, muscle sympathetic nerve activity (MSNA), and head rotation were measured during HDR in 11 young (26 +/- 1 years) and 11 older (64 +/- 1 years) subjects in the prone posture. Five older subjects performed head rotation (chin to chest) in the lateral decubitus position, which simulates HDR but does not alter afferent inputs from the vestibular system. MSNA responses to HDR were significantly attenuated in older as compared with young subjects (P<0.01). MSNA increased in the older subjects by only 12 +/- 5% as compared with 85 +/- 16% in the young. Furthermore, HDR elicited significant reductions in mean arterial blood pressure in older (Delta-6 +/- 1 mm Hg; P<0.01) but not young subjects (Delta1 +/- 1 mm Hg). In contrast to HDR, head rotation performed in the lateral decubitus position did not elicit hypotension. MSNA responses to baroreceptor unloading and the cold pressor test were not different between the age groups. CONCLUSIONS: These data indicate that aging attenuates the vestibulosympathetic reflex in humans and may contribute to the increased prevalence of orthostatic hypotension with age.

  12. Baclofen decreases methamphetamine self-administration in rats.

    PubMed

    Ranaldi, Robert; Poeggel, Kerry

    2002-07-02

    In the present study we tested the hypothesis that baclofen, a GABA-B receptor agonist, attenuates methamphetamine self-administration. Fifteen rats were trained to self-administer i.v. injections of methamphetamine (0, 0.0625, 0.125 and 0.25 mg/kg/injection) on a progressive ratio schedule of reinforcement, and then were tested under the influence of two doses of baclofen (2.5 or 5.0 mg/kg, i.p.). Baclofen significantly reduced break points at all doses of methamphetamine, producing a dose-orderly shift of the methamphetamine dose-response function to the right. These data suggest that pretreatment with baclofen reduces methamphetamine reward. These data are consistent with other studies showing impairment of drug reward after pretreatment with baclofen and add further support to the idea that GABA-B agonists may be useful in the treatment of drug addiction.

  13. S-Allylmercaptocysteine Attenuates Cisplatin-Induced Nephrotoxicity through Suppression of Apoptosis, Oxidative Stress, and Inflammation

    PubMed Central

    Zhu, Xiaosong; Jiang, Xiaoyan; Li, Ang; Zhao, Zhongxi; Li, Siying

    2017-01-01

    Cisplatin is a potent chemotherapeutic agent, but its clinical usage is limited by nephrotoxicity. S-allylmercaptocysteine (SAMC), one of the water-soluble organosulfur garlic derivatives, has antioxidant and anti-inflammatory properties and plays an important role in protecting cells from apoptosis. This study aims to examine the protective effects of SAMC on cisplatin nephrotoxicity and to explore the mechanism of its renoprotection. Rats were treated with cisplatin with or without pre-treatment with SAMC. Renal function, histological change, oxidative stress markers and antioxidant enzyme activities were investigated. Apoptotic marker, nuclearfactor (NF)-κB activity, expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase 1 (NQO1) and inflammatory cytokines were also examined. The effect of SAMC on cell viability and apoptosis was examined in cultured human kidney (HK-2) cells. SAMC was confirmed to significantly attenuate cisplatin-induced renal damage by using histological pathology and molecular biological method. Pre-treatment with SAMC reduced NF-κB activity, up-regulated Nrf2 and NQO1 expression and down-regulated inflammatory cytokine levels after cisplatin administration. Cisplatin-induced apoptosis in HK-2 cells was significantly attenuated by SAMC. Thus our results suggest that SAMC could be a potential therapeutic agent in the treatment of the cisplatin-induced nephrotoxicity through its anti-apoptotic, anti-oxidant and anti-inflammatory effects. PMID:28230744

  14. High plasma norepinephrine attenuates the dynamic heart rate response to vagal stimulation.

    PubMed

    Miyamoto, Tadayoshi; Kawada, Toru; Takaki, Hiroshi; Inagaki, Masashi; Yanagiya, Yusuke; Jin, Yintie; Sugimachi, Masaru; Sunagawa, Kenji

    2003-06-01

    To better understand the pathophysiological significance of high plasma norepinephrine (NE) concentration in regulating heart rate (HR), we examined the interactions between high plasma NE and dynamic vagal control of HR. In anesthetized rabbits with sinoaortic denervation and vagotomy, using a binary white noise sequence (0-10 Hz) for 10 min, we stimulated the right vagus and estimated the transfer function from vagal stimulation to HR response. The transfer function approximated a first-order low-pass filter with pure delay. Infusion of NE (100 microg. kg(-1) x h(-1) iv) attenuated the dynamic gain from 6.2 +/- 0.8 to 3.9 +/- 1.2 beats x min(-1) x Hz(-1) (n = 7, P < 0.05) without affecting the corner frequency or pure delay. Simultaneous intravenous administration of phentolamine (1 mg x kg(-1) x h(-1)) and NE (100 microg x kg(-1) x h(-1)) abolished the inhibitory effect of NE on the dynamic gain (6.3 +/- 0.8 vs. 6.4 +/- 1.3 beats x min(-1) x Hz(-1), not significant, n = 7). The inhibitory effect of NE at infusion rates of 10, 50, and 100 microg x kg(-1) x h(-1) on dynamic vagal control of HR was dose-dependent (n = 5). In conclusion, high plasma NE attenuated the dynamic HR response to vagal stimulation, probably via activation of alpha-adrenergic receptors on the preganglionic and/or postganglionic cardiac vagal nerve terminals.

  15. Blockade of neuronal dopamine D2 receptor attenuates morphine tolerance in mice spinal cord

    PubMed Central

    Dai, Wen-Ling; Xiong, Feng; Yan, Bing; Cao, Zheng-Yu; Liu, Wen-Tao; Liu, Ji-Hua; Yu, Bo-Yang

    2016-01-01

    Tolerance induced by morphine remains a major unresolved problem and significantly limits its clinical use. Recent evidences have indicated that dopamine D2 receptor (D2DR) is likely to be involved in morphine-induced antinociceptive tolerance. However, its exact effect and molecular mechanism remain unknown. In this study we examined the effect of D2DR on morphine antinociceptive tolerance in mice spinal cord. Chronic morphine treatment significantly increased levels of D2DR in mice spinal dorsal horn. And the immunoreactivity of D2DR was newly expressed in neurons rather than astrocytes or microglia both in vivo and in vitro. Blockade of D2DR with its antagonist (sulpiride and L-741,626, i.t.) attenuated morphine antinociceptive tolerance without affecting basal pain perception. Sulpiride (i.t.) also down-regulated the expression of phosphorylation of NR1, PKC, MAPKs and suppressed the activation of astrocytes and microglia induced by chronic morphine administration. Particularly, D2DR was found to interact with μ opioid receptor (MOR) in neurons, and chronic morphine treatment enhanced the MOR/D2DR interactions. Sulpiride (i.t.) could disrupt the MOR/D2DR interactions and attenuate morphine tolerance, indicating that neuronal D2DR in the spinal cord may be involved in morphine tolerance possibly by interacting with MOR. These results may present new opportunities for the treatment and management of morphine-induced antinociceptive tolerance which often observed in clinic. PMID:28004735

  16. Paeoniflorin attenuates hippocampal damage in a rat model of vascular dementia

    PubMed Central

    Zhang, Ying; Wang, Li-Li; Wu, Yan; Wang, Ning; Wang, Shang-Ming; Zhang, Bin; Shi, Cui-Ge; Zhang, Shu-Cheng

    2016-01-01

    Paeoniflorn (PF), the principal bioactive component of Paeoniae radix prescribed in traditional Chinese medicine, possesses a wide range of biological effects and exhibits neuroprotective effects in numerous diseases. Previous studies have demonstrated that PF significantly attenuates memory impairment in rats with vascular dementia (VD). In the present study, a bilateral common carotid artery occlusion (BCCAO) rat model was used to explore the underlying mechanisms of PF. The expression levels of neuron-specific enolase (NSE), S100β, B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein, cytochrome c and brain-derived neurotrophic factor (BDNF) in the hippocampus were measured by western blot analysis. The results showed that administration of PF for 28 days significantly decreased the expression levels of NSE and S100β, both sensitive markers for brain damage, in vascular dementia (VD) model rats. In addition, PF inhibited the initiation of apoptotic cell death and attenuated the decreased expression levels of BDNF induced by bilateral common carotid artery occlusion. These data confirm the neuroprotective effects of PF on VD and provide a novel insight into the long-term use of PF as a potential treatment in the stages of early cognitive impairment in VD. PMID:28101164

  17. Cardiovascular responses to intrathecal administration of endomorphins in anesthetized rats.

    PubMed

    Wang, Chang-Lin; Yu, Ye; Lai, Lu-Hao; Cui, Yun; Wang, Xiang; Wang, Rui

    2007-04-01

    Endomorphins (EMs), the endogenous, potent and selective mu-opioid receptor agonists, have been shown to decrease systemic arterial pressure (SAP) in rats after intravenous (i.v.) administration. In the present study, cardiovascular responses to intrathecal (i.t.) injection of EMs were investigated in urethane-anesthetized rats. It is noteworthy that EMs elicited decreases in SAP and heart rate (HR) in a dose-dependent manner; 10-300nmol/kg were injected intrathecally. Furthermore, these vasodepressor and bradycardic effects were significantly antagonized by naloxone (0.5mg/kg, i.t.). Interestingly, i.t. (5mg/kg) or i.v. (50mg/kg) administrations of N(omega)-nitro-l-arginine methylester (l-NAME) attenuated the vasodepressor and bradycardic effects. Moreover, pretreatment of the rats with muscarinic receptor antagonist atropine (2mg/kg, i.v.) and alpha-adrenoceptor antagonist phentolamine (1mg/kg, i.v.) significantly reduced the vasodepressor effects of EMs. Nevertheless, pretreatment with beta-adrenoceptor antagonist propranolol (2mg/kg, i.v.) could only block the bradycardia effects induced by EMs, but had no significant effects on the hypotension. In summary, all the results suggested that i.t. administration of EMs decreased SAP and HR which were possibly mediated by the activation of opioid receptors in the rat spinal cord. In addition, nitric oxide (NO) release in both the spinal cord and in peripheral tissues might regulate the cardiovascular activities of EMs, and the muscarinic receptor and adrenoceptor played an important role in the regulation of the cardiovascular responses to i.t. administration of EMs.

  18. Senior Administrators Should Have Administrative Contracts.

    ERIC Educational Resources Information Center

    Posner, Gary J.

    1987-01-01

    Recognizing that termination is viewed by the employee as the equivalent to capital punishment of a career, an administrative contract can reduce the emotional and financial entanglements that often result. Administrative contracts are described. (MLW)

  19. Correction for acoustic attenuation effects in optoacoustic tomographic reconstructions

    NASA Astrophysics Data System (ADS)

    Deán-Ben, X. Luís; Razansky, Daniel; Ntziachristos, Vasilis

    2011-07-01

    The feasibility of correcting for the effects of acoustic attenuation in optoacoustic tomographic reconstructions obtained with model-based inversion is shown in this work. Acoustic attenuation is a physical phenomenon that takes place inevitably in actual acoustic media and becomes significant at high ultrasonic frequencies. The frequency dependence of acoustic attenuation and the associated dispersion lead to reduction of amplitude and broadening of the optoacoustic signals, which in turn cause, respectively, quantification errors and loss of resolution in the reconstructed images. In this work we imaged an agar phantom with embedded microparticles in three different scenarios, namely with the signals acquired with no attenuation, with the signals collected by placing an attenuating sample in between the phantom and the ultrasonic transducer and with the signals corrected for the effects of acoustic attenuation. The results obtained show that the quantification inaccuracies and the loss of resolution of the images can be partially corrected at the expense of introducing noise at high spatial frequencies due to the amplification of the high frequency components of the noise in the signals.

  20. Pyruvate attenuates cardiac dysfunction and oxidative stress in isoproterenol-induced cardiotoxicity.

    PubMed

    Ojha, Shreesh; Goyal, Sameer; Kumari, Santosh; Arya, Dharamvir Singh

    2012-05-01

    Pyruvate, a potent endogenous antioxidant and an important metabolic fuel is essential for the cardiac function and tissue defense mechanism. The present study was evaluated to investigate whether pyruvate attenuates the development of cardiotoxicity in isoproterenol (ISO)-induced myocardial infarction by assessing hemodynamic, biochemical and histopathological parameters. Subcutaneous injection of ISO (85 mg/kg) administered for 2 days at an interval of 24h was used for induction of cardiotoxicity. ISO administration significantly decreased arterial pressure indices, heart rate, contractility {(+)LVdP/dt} and relaxation {(-)LVdP/dt} and increased left ventricular end-diastolic pressure. In addition, a significant reduction in activities of myocardial creatine phosphokinase-MB, lactate dehydrogenase, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione levels along with increase in thiobarbituric acid reactive substances were also observed following ISO administration. However, pretreatment with pyruvate (0.25, 0.5 and 1.0 g/kg, p.o.) favorably modulated all most every studied parameters in ISO-induced myocardial injury. Furthermore, protective effect of pyruvate was confirmed by histopathological studies. Rats pretreated only with pyruvate did not produce significant change in hemodynamic, biochemical and histopathological parameters. Pyruvate at 0.50 and 1.0 g/kg doses was found to exert optimal cardioprotective effect against ISO-induced myocardial infarction. The results of our study suggest that pyruvate possessing antioxidant activity has a significant cardioprotective effect against ISO-induced myocardial injury.

  1. SEISMIC ATTENUATION FOR RESERVOIR CHARACTERIZATION

    SciTech Connect

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

    2002-07-01

    In fully-saturated rock and at ultrasonic frequencies, the microscopic squirt flow induced between the stiff and soft parts of the pore space by an elastic wave is responsible for velocity-frequency dispersion and attenuation. In the seismic frequency range, it is the macroscopic cross-flow between the stiffer and softer parts of the rock. We use the latter hypothesis to introduce simple approximate equations for velocity-frequency dispersion and attenuation in a fully water saturated reservoir. The equations are based on the assumption that in heterogeneous rock and at a very low frequency, the effective elastic modulus of the fully-saturated rock can be estimated by applying a fluid substitution procedure to the averaged (upscaled) dry frame whose effective porosity is the mean porosity and the effective elastic modulus is the Backus-average (geometric mean) of the individual dry-frame elastic moduli of parts of the rock. At a higher frequency, the effective elastic modulus of the saturated rock is the Backus-average of the individual fully-saturated-rock elastic moduli of parts of the rock. The difference between the effective elastic modulus calculated separately by these two methods determines the velocity-frequency dispersion. The corresponding attenuation is calculated from this dispersion by using (e.g.) the standard linear solid attenuation model.

  2. Ancient administrative handwritten documents: X-ray analysis and imaging.

    PubMed

    Albertin, F; Astolfo, A; Stampanoni, M; Peccenini, Eva; Hwu, Y; Kaplan, F; Margaritondo, G

    2015-03-01

    Handwritten characters in administrative antique documents from three centuries have been detected using different synchrotron X-ray imaging techniques. Heavy elements in ancient inks, present even for everyday administrative manuscripts as shown by X-ray fluorescence spectra, produce attenuation contrast. In most cases the image quality is good enough for tomography reconstruction in view of future applications to virtual page-by-page `reading'. When attenuation is too low, differential phase contrast imaging can reveal the characters from refractive index effects. The results are potentially important for new information harvesting strategies, for example from the huge Archivio di Stato collection, objective of the Venice Time Machine project.

  3. Ancient administrative handwritten documents: X-ray analysis and imaging

    PubMed Central

    Albertin, F.; Astolfo, A.; Stampanoni, M.; Peccenini, Eva; Hwu, Y.; Kaplan, F.; Margaritondo, G.

    2015-01-01

    Handwritten characters in administrative antique documents from three centuries have been detected using different synchrotron X-ray imaging techniques. Heavy elements in ancient inks, present even for everyday administrative manuscripts as shown by X-ray fluorescence spectra, produce attenuation contrast. In most cases the image quality is good enough for tomography reconstruction in view of future applications to virtual page-by-page ‘reading’. When attenuation is too low, differential phase contrast imaging can reveal the characters from refractive index effects. The results are potentially important for new information harvesting strategies, for example from the huge Archivio di Stato collection, objective of the Venice Time Machine project. PMID:25723946

  4. Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone attenuates postincisional pain by regulating macrophage polarization

    SciTech Connect

    Hasegawa-Moriyama, Maiko; Ohnou, Tetsuya; Godai, Kohei; Kurimoto, Tae; Nakama, Mayo; Kanmura, Yuichi

    2012-09-14

    Highlights: Black-Right-Pointing-Pointer Rosiglitazone attenuated postincisional pain. Black-Right-Pointing-Pointer Rosiglitazone alters macrophage polarization to F4/80{sup +}CD206{sup +} M2 macrophages at the incisional sites. Black-Right-Pointing-Pointer Transplantation of rosiglitazone-treated macrophages produced analgesic effects. -- Abstract: Acute inflammation triggered by macrophage infiltration to injured tissue promotes wound repair and may induce pain hypersensitivity. Peroxisome proliferator-activated receptor {gamma} (PPAR){gamma} signaling is known to regulate heterogeneity of macrophages, which are often referred to as classically activated (M1) and alternatively activated (M2) macrophages. M1 macrophages have considerable antimicrobial activity and produce a wide variety of proinflammatory cytokines. In contrast, M2 macrophages are involved in anti-inflammatory and homeostatic functions linked to wound healing and tissue repair. Although it has been suggested that PPAR{gamma} agonists attenuate pain hypersensitivity, the molecular mechanism of macrophage-mediated effects of PPAR{gamma} signaling on pain development has not been explored. In this study, we investigated the link between the phenotype switching of macrophage polarization induced by PPAR{gamma} signaling and the development of acute pain hypersensitivity. Local administration of rosiglitazone significantly ameliorated hypersensitivity to heat and mechanical stimuli, and paw swelling. Consistent with the down-regulation of nuclear factor {kappa}B (NF{kappa}B) phosphorylation by rosiglitazone at the incisional sites, the number of F4/80{sup +}iNOS{sup +} M1 macrophages was decreased whereas numbers of F4/80{sup +}CD206{sup +} M2 macrophages were increased in rosiglitazone-treated incisional sites 24 h after the procedure. In addition, gene induction of anti-inflammatory M2-macrophage-associated markers such as arginase1, FIZZ1 and interleukin (IL)-10 were significantly increased, whereas

  5. Attenuation of insulin resistance, metabolic syndrome and hepatic oxidative stress by resveratrol in fructose-fed rats.

    PubMed

    Bagul, Pankaj K; Middela, Harish; Matapally, Saidulu; Padiya, Raju; Bastia, Tanmay; Madhusudana, K; Reddy, B Raghunath; Chakravarty, Sumana; Banerjee, Sanjay K

    2012-09-01

    Metabolic syndrome and oxidative stress are common complications of type 2 diabetes mellitus. The present study was designed to determine whether resveratrol, a widely used nutritional supplement, can improve insulin sensitivity, metabolic complication as well as hepatic oxidative stress in fructose-fed rats. Male Sprague Dawley rats (180-200 g) were divided into four groups with 8 animals each. Fructose-fed insulin resistant group (Dia) animals were fed 65% fructose (Research diet, USA) for a period of 8 weeks, whereas control group (Con) animals were fed 65% cornstarch (Research Diet, USA). Resveratrol, 10 mg/kg/day (Dia+Resv) or metformin 300 mg/kg/day (Dia+Met) were administered orally to the 65% fructose-fed rats for 8 weeks. At the end of the feeding schedule, Dia group had insulin resistance along with increased blood glucose, triglyceride, uric acid and nitric oxide (NO) levels. Significant (p<0.05) increase in hepatic TBARS and conjugated dienes, and significant (p<0.05) decrease in hepatic SOD and vitamin C was observed in Dia group compared to Con group. Administration of metformin or resveratrol significantly (p<0.05) normalized all the altered metabolic parameters. However, a marked insulin sensitizing action was only observed in the Dia+Resv group. Similarly, while metformin administration failed to normalize the increased TBARS levels and decreased SOD activity, resveratrol showed a more promising effect of all oxidative stress parameters measured in the present study. Attenuation of hepatic oxidative stress in fructose-fed rat liver after resveratrol administration was associated with significant (p<0.05) increase in nuclear level of NRF2 compared with other groups. The present study demonstrates that resveratrol is more effective than metformin in improving insulin sensitivity, and attenuating metabolic syndrome and hepatic oxidative stress in fructose-fed rats.

  6. Attenuating endogenous Fgfr2b ligands during bleomycin-induced lung fibrosis does not compromise murine lung repair

    PubMed Central

    MacKenzie, BreAnne; Henneke, Ingrid; Hezel, Stefanie; Al Alam, Denise; El Agha, Elie; Chao, Cho-Ming; Quantius, Jennifer; Wilhelm, Jochen; Jones, Matthew; Goth, Kerstin; Li, Xiaokun; Seeger, Werner; Königshoff, Melanie; Herold, Susanne; Rizvanov, Albert A.; Günther, Andreas

    2015-01-01

    Fibroblast growth factors (Fgfs) mediate organ repair. Lung epithelial cell overexpression of Fgf10 postbleomycin injury is both protective and therapeutic, characterized by increased survival and attenuated fibrosis. Exogenous administration of FGF7 (palifermin) also showed prophylactic survival benefits in mice. The role of endogenous Fgfr2b ligands on bleomycin-induced lung fibrosis is still elusive. This study reports the expression of endogenous Fgfr2b ligands, receptors, and signaling targets in wild-type mice following bleomycin lung injury. In addition, the impact of attenuating endogenous Fgfr2b-ligands following bleomycin-induced fibrosis was tested by using a doxycycline (dox)-based inducible, soluble, dominant-negative form of the Fgfr2b receptor. Double-transgenic (DTG) Rosa26rtTA/+;tet(O)solFgfr2b mice were validated for the expression and activity of soluble Fgfr2b (failure to regenerate maxillary incisors, attenuated recombinant FGF7 signal in the lung). As previously reported, no defects in lung morphometry were detected in DTG (+dox) mice exposed from postnatal days (PN) 1 through PN105. Female single-transgenic (STG) and DTG mice were subjected to various levels of bleomycin injury (1.0, 2.0, and 3.0 U/kg). Fgfr2b ligands were attenuated either throughout injury (days 0–11; days 0–28) or during later stages (days 6–28 and 14–28). No significant changes in survival, weight, lung function, confluent areas of fibrosis, or hydroxyproline deposition were detected in DTG mice. These results indicate that endogenous Fgfr2b ligands do not significantly protect against bleomycin injury, nor do they expedite the resolution of bleomycin-induced lung injury in mice. PMID:25820524

  7. Attenuating endogenous Fgfr2b ligands during bleomycin-induced lung fibrosis does not compromise murine lung repair.

    PubMed

    MacKenzie, BreAnne; Henneke, Ingrid; Hezel, Stefanie; Al Alam, Denise; El Agha, Elie; Chao, Cho-Ming; Quantius, Jennifer; Wilhelm, Jochen; Jones, Matthew; Goth, Kerstin; Li, Xiaokun; Seeger, Werner; Königshoff, Melanie; Herold, Susanne; Rizvanov, Albert A; Günther, Andreas; Bellusci, Saverio

    2015-05-15

    Fibroblast growth factors (Fgfs) mediate organ repair. Lung epithelial cell overexpression of Fgf10 postbleomycin injury is both protective and therapeutic, characterized by increased survival and attenuated fibrosis. Exogenous administration of FGF7 (palifermin) also showed prophylactic survival benefits in mice. The role of endogenous Fgfr2b ligands on bleomycin-induced lung fibrosis is still elusive. This study reports the expression of endogenous Fgfr2b ligands, receptors, and signaling targets in wild-type mice following bleomycin lung injury. In addition, the impact of attenuating endogenous Fgfr2b-ligands following bleomycin-induced fibrosis was tested by using a doxycycline (dox)-based inducible, soluble, dominant-negative form of the Fgfr2b receptor. Double-transgenic (DTG) Rosa26(rtTA/+);tet(O)solFgfr2b mice were validated for the expression and activity of soluble Fgfr2b (failure to regenerate maxillary incisors, attenuated recombinant FGF7 signal in the lung). As previously reported, no defects in lung morphometry were detected in DTG (+dox) mice exposed from postnatal days (PN) 1 through PN105. Female single-transgenic (STG) and DTG mice were subjected to various levels of bleomycin injury (1.0, 2.0, and 3.0 U/kg). Fgfr2b ligands were attenuated either throughout injury (days 0-11; days 0-28) or during later stages (days 6-28 and 14-28). No significant changes in survival, weight, lung function, confluent areas of fibrosis, or hydroxyproline deposition were detected in DTG mice. These results indicate that endogenous Fgfr2b ligands do not significantly protect against bleomycin injury, nor do they expedite the resolution of bleomycin-induced lung injury in mice.

  8. Ethanol co-administration moderates 3,4-methylenedioxymethamphetamine effects on human physiology.

    PubMed

    Dumont, G J H; Kramers, C; Sweep, F C G J; Willemsen, J J; Touw, D J; Schoemaker, R C; van Gerven, J M A; Buitelaar, J K; Verkes, R J

    2010-02-01

    Alcohol is frequently used in combination with 3,4-methylenedioxymethamphetamine (MDMA). Both drugs affect cardiovascular function, hydration and temperature regulation, but may have partly opposing effects. The present study aims to assess the acute physiologic effects of (co-) administration of MDMA and ethanol over time. A four-way, double blind, randomized, crossover, placebo-controlled study in 16 healthy volunteers (9 male and 7 female) between the ages of 18 and 29. MDMA (100 mg) was given orally and blood ethanol concentration was maintained at pseudo-steady state levels of 0.6 per thousand by a three-hour 10% intravenous ethanol clamp. Cardiovascular function, temperature and hydration measures were recorded throughout the study days. Ethanol did not significantly affect physiologic function, with the exception of a short lasting increase in heart rate. MDMA potently increased heart rate and blood pressure and induced fluid retention as well as an increase in temperature. Co-administration of ethanol with MDMA did not affect cardiovascular function compared to the MDMA alone condition, but attenuated the effects of MDMA on fluid retention and showed a trend for attenuation of MDMA-induced temperature increase. In conclusion, co-administration of ethanol and MDMA did not exacerbate physiologic effects compared to all other drug conditions, and moderated some effects of MDMA alone.

  9. Veterans Health Administration

    MedlinePlus

    ... code here VA » Veterans Health Administration Veterans Health Administration Marine Continues to Serve by Serving Veterans David ... Read more » VA Medical Centers The Veterans Health Administration is home to the United States’ largest integrated ...

  10. Ferrite attenuator modulation improves antenna performance

    NASA Technical Reports Server (NTRS)

    Hooks, J. C.; Larson, S. G.; Shorkley, F. H.; Williams, B. T.

    1970-01-01

    Ferrite attenuator inserted into appropriate waveguide reduces the gain of the antenna element which is causing interference. Modulating the ferrite attenuator to change the antenna gain at the receive frequency permits ground tracking until the antenna is no longer needed.

  11. Tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury in different models possibly through suppression of NF-κB activation.

    PubMed

    Zhao, Zhanzhong; Tang, Xiangfang; Zhao, Xinghui; Zhang, Minhong; Zhang, Weijian; Hou, Shaohua; Yuan, Weifeng; Zhang, Hongfu; Shi, Lijun; Jia, Hong; Liang, Lin; Lai, Zhi; Gao, Junfeng; Zhang, Keyu; Fu, Ling; Chen, Wei

    2014-07-01

    Tylvalosin, a new broad-spectrum, third-generation macrolides, may exert a variety of pharmacological activities. Here, we report on its anti-oxidative and anti-inflammatory activity in RAW 264.7 macrophages and mouse treated with lipopolysaccharide (LPS) as well as piglet challenged with porcine reproductive and respiratory syndrome virus (PRRSV). Tylvalosin treatment markedly decreased IL-8, IL-6, IL-1β, PGE2, TNF-α and NO levels in vitro and in vivo. LPS and PRRSV-induced reactive oxygen species (ROS) production, and the lipid peroxidation in mice lung tissues reduced after tylvalosin treatments. In mouse acute lung injury model induced by LPS, tylvalosin administration significantly attenuated tissues injury, and reduced the inflammatory cells recruitment and activation. The evaluated phospholipase A2 (PLA2) activity and the increased expressions of cPLA2-IVA, p-cPLA2-IVA and sPLA2-IVE were lowered by tylvalosin. Consistent with the mouse results, tylvalosin pretreatment attenuated piglet lung scores with improved growth performance and normal rectal temperature in piglet model induced by PRRSV. Furthermore, tylvalosin attenuated the IκBα phosphorylation and degradation, and blocked the NF-κB p65 translocation. These results indicate that in addition to its direct antimicrobial effect, tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury through suppression of NF-κB activation.

  12. Wogonin Induces Eosinophil Apoptosis and Attenuates Allergic Airway Inflammation

    PubMed Central

    Dorward, David A.; Sharma, Sidharth; Rennie, Jillian; Felton, Jennifer M.; Alessandri, Ana L.; Duffin, Rodger; Schwarze, Jurgen; Haslett, Christopher; Rossi, Adriano G.

    2015-01-01

    Rationale: Eosinophils are key effector cells in allergic diseases, including allergic rhinitis, eczema, and asthma. Their tissue presence is regulated by both recruitment and increased longevity at inflamed sites. Objectives: To investigate the ability of the flavone wogonin to induce eosinophil apoptosis in vitro and attenuate eosinophil-dominant allergic inflammation in vivo in mice. Methods: Human and mouse eosinophil apoptosis in response to wogonin was investigated by cellular morphology, flow cytometry, mitochondrial membrane permeability, and pharmacological caspase inhibition. Allergic lung inflammation was modeled in mice sensitized and challenged with ovalbumin. Bronchoalveolar lavage (BAL) and lung tissue were examined for inflammation, mucus production, and inflammatory mediator production. Airway hyperresponsiveness to aerosolized methacholine was measured. Measurements and Main Results: Wogonin induced time- and concentration-dependent human and mouse eosinophil apoptosis in vitro. Wogonin-induced eosinophil apoptosis occurred with activation of caspase-3 and was inhibited by pharmacological caspase inhibition. Wogonin administration attenuated allergic airway inflammation in vivo with reductions in BAL and interstitial eosinophil numbers, increased eosinophil apoptosis, reduced airway mucus production, and attenuated airway hyperresponsiveness. This wogonin-induced reduction in allergic airway inflammation was prevented by concurrent caspase inhibition in vivo. Conclusions: Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation, suggesting that it has therapeutic potential for the treatment of allergic inflammation in humans. PMID:25629436

  13. Calcitriol attenuates cardiac remodeling and dysfunction in a murine model of polycystic ovary syndrome.

    PubMed

    Gao, Ling; Cao, Jia-Tian; Liang, Yan; Zhao, Yi-Chao; Lin, Xian-Hua; Li, Xiao-Cui; Tan, Ya-Jing; Li, Jing-Yi; Zhou, Cheng-Liang; Xu, Hai-Yan; Sheng, Jian-Zhong; Huang, He-Feng

    2016-05-01

    Polycystic ovary syndrome (PCOS) is a complex reproductive and metabolic disorder affecting 10 % of reproductive-aged women, and is well associated with an increased prevalence of cardiovascular risk factors. However, there are few data concerning the direct association of PCOS with cardiac pathologies. The present study aims to investigate the changes in cardiac structure, function, and cardiomyocyte survival in a PCOS model, and explore the possible effect of calcitriol administration on these changes. PCOS was induced in C57BL/6J female mice by chronic dihydrotestosterone administration, as evidenced by irregular estrous cycles, obesity and dyslipidemia. PCOS mice progressively developed cardiac abnormalities including cardiac hypertrophy, interstitial fibrosis, myocardial apoptosis, and cardiac dysfunction. Conversely, concomitant administration of calcitriol significantly attenuated cardiac remodeling and cardiomyocyte apoptosis, and improved cardiac function. Molecular analysis revealed that the beneficial effect of calcitriol was associated with normalized autophagy function by increasing phosphorylation levels of AMP-activated protein kinase and inhibiting phosphorylation levels of mammalian target of rapamycin complex. Our findings provide the first evidence for the presence of cardiac remodeling in a PCOS model, and vitamin D supplementation may be a potential therapeutic strategy for the prevention and treatment of PCOS-related cardiac remodeling.

  14. Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury.

    PubMed

    Ma, Zhicong; Han, Qi; Wang, Xiaolei; Ai, Zisheng; Zheng, Yongjun

    2016-01-01

    Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the carbohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro-inflammatory response by recruiting and activating lymphocytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin (MCP), a gal3 inhibitor, reduces gal3 expression in dorsal root ganglions. MCP treatment also inhibits SNL-induced gal3 expression in primary rat microglia. SNL results in an increased activation of autophagy that contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of MCP significantly suppresses SNL-induced autophagy activation. MCP also inhibits lipopolysaccharide (LPS)-induced autophagy in cultured microglia in vitro. MCP further decreases LPS-induced expression of proinflammatory mediators including IL-1β, TNF-α and IL-6 by regulating autophagy. Intrathecal administration of MCP results in adecreased mechanical and cold hypersensitivity following SNL. These results demonstrated that gal3 inhibition is associated with the suppression of SNL-induced inflammatory process andneurophathic pain attenuation.

  15. Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury

    PubMed Central

    Ai, Zisheng; Zheng, Yongjun

    2016-01-01

    Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the carbohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro-inflammatory response by recruiting and activating lymphocytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin (MCP), a gal3 inhibitor, reduces gal3 expression in dorsal root ganglions. MCP treatment also inhibits SNL-induced gal3 expression in primary rat microglia. SNL results in an increased activation of autophagy that contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of MCP significantly suppresses SNL-induced autophagy activation. MCP also inhibits lipopolysaccharide (LPS)-induced autophagy in cultured microglia in vitro. MCP further decreases LPS-induced expression of proinflammatory mediators including IL-1β, TNF-α and IL-6 by regulating autophagy. Intrathecal administration of MCP results in adecreased mechanical and cold hypersensitivity following SNL. These results demonstrated that gal3 inhibition is associated with the suppression of SNL-induced inflammatory process andneurophathic pain attenuation. PMID:26872020

  16. Metformin attenuates gefitinib-induced exacerbation of pulmonary fibrosis by inhibition of TGF-β signaling pathway.

    PubMed

    Li, Li; Huang, Wenting; Li, Kunlin; Zhang, Kejun; Lin, Caiyu; Han, Rui; Lu, Conghua; Wang, Yubo; Chen, Hengyi; Sun, Fenfen; He, Yong

    2015-12-22

    Interstitial lung disease (ILD) is a serious side-effect of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment. Therefore, it is necessary to study underlying mechanisms for the development of pulmonary fibrosis induced by EGFR-TKI and potential approaches to attenuate it. Metformin is a well-established and widely prescribed oral hypoglycemic drug, and has gained attention for its potential anticancer effects. Recent reports have also demonstrated its role in inhibiting epithelial-mesenchymal transition and fibrosis. However, it is unknown whether metformin attenuates EGFR-TKI-induced pulmonary fibrosis. The effect of metformin on EGFR-TKI-induced exacerbation of pulmonary fibrosis was examined in vitro and in vivo using MTT, Ki67 incorporation assay, flow cytometry, immunostaining, Western blot analysis, and a bleomycin-induced pulmonary fibrosis rat model. We found that in lung HFL-1 fibroblast cells, TGF-β or conditioned medium from TKI-treated lung cancer PC-9 cells or conditioned medium from TKI-resistant PC-9GR cells, induced significant fibrosis, as shown by increased expression of Collegen1a1 and α-actin, while metformin inhibited expression of fibrosis markers. Moreover, metformin decreased activation of TGF-β signaling as shown by decreased expression of pSMAD2 and pSMAD3. In vivo, oral administration of gefitinib exacerbated bleomycin-induced pulmonary fibrosis in rats, as demonstrated by HE staining and Masson staining. Significantly, oral co-administration of metformin suppressed exacerbation of bleomycin-induced pulmonary fibrosis by gefitinib. We have shown that metformin attenuates gefitinib-induced exacerbation of TGF-β or bleomycin-induced pulmonary fibrosis. These observations indicate metformin may be combined with EGFR-TKI to treat NSCLC patients.

  17. Morphine Attenuates Testosterone Response to Central Injection of Kisspeptin in Male Rats

    PubMed Central

    Mahmoudi, Fariba; Khazali, Homayoun; Janahmadi, Mahyar

    2014-01-01

    Background Kisspeptin and naloxone stimulate the reproductive axis while morphine inhibits its function. We have investigated the effect of central injection of kisspeptin-10 on mean plasma testosterone concentration in morphine or naloxone pretreated rats. Materials and Methods In this experimental study, 60 male Wistar rats that were divid- ed into 12 groups (n=5 per group) received saline, kisspeptin (1 nmol, ICV), naloxone (2 mg/kg, subcutaneously), morphine (5 or 10 mg/kg, sc) or co-administrations of kisspeptin, morphine and naloxone at 09:00 - 09:30. In the co-administrated groups, kisspeptin was injected 15 minutes following morphine or naloxone injections. Blood samples were collected 60 minutes following injections via the tail vein. Plasma testosterone concentration was measured by a rat testosterone ELISA kit. Results Central injection of kisspeptin or subcutaneous injection of naloxone significantly increased the mean plasma testosterone concentration compared to saline while subcutaneous injections of different doses of morphine (5 or 10 mg/kg) significantly decreased testosterone compared to saline. The results revealed that morphine significantly attenuated the testosterone increase after kisspeptin injection compared to kisspeptin while a stimulatory additive effect was observed in the kisspeptin/naloxone group compared to either naloxone or kisspeptin. Conclusion Morphine and kisspeptin systems may interact with each other to control the hypothalamic-pituitary-gonadal (HPG) axis. PMID:25083187

  18. Intravenous injection of Xuebijing attenuates acute kidney injury in rats with paraquat intoxication

    PubMed Central

    Xu, Jia-jun; Zhen, Jian-tao; Tang, Li; Lin, Qing-ming

    2017-01-01

    BACKGROUND: The study aimed to investigate the therapeutic benefits of intravenous Xuebijing on acute kidney injury (AKI) in rats with paraquat intoxication. METHODS: Male Sprague-Dawley rats were randomly divided equally into three groups: sham group (n=8), paraquat group (n=8) and Xuebijing-treated group (n=8) using a random number table. The rats were intraperitoneally injected with 50 mg/kg of paraquat. One hour after paraquat administration, the rats were treated intravenously with Xuebijing (8 mL/kg). At 12 hours after paraquat administration, serum was collected to evaluate kidney function, then the rats were sacrificed and kidney samples were immediately harvested. AKI scores were evaluated by renal histopathology and pro-inflammatory cytokines mRNA levels in kidney were assayed using real-time RT-PCR. RESULTS: Serum urea nitrogen, creatinine and AKI scores were significantly higher in the paraquat group, compared with the sham group (P<0.05, respectively). Moreover, interleukin (IL)-1β, IL-6 and TNF-α mRNA levels were significantly higher in the paraquat group (P<0.01, respectively). However, intravenous Xuebijing significantly decreased serum urea nitrogen, creatinine, AKI scores and IL-1β, IL-6 and TNF-α mRNA levels, compared with the paraquat group (P<0.05, respectively). CONCLUSION: Intravenous Xuebijing attenuates AKI following paraquat poisoning by suppressing inflammatory response. PMID:28123623

  19. Angiopoietin-2 attenuates angiotensin II-induced aortic aneurysm and atherosclerosis in apolipoprotein E-deficient mice

    PubMed Central

    Yu, Hongyou; Moran, Corey S.; Trollope, Alexandra F.; Woodward, Lynn; Kinobe, Robert; Rush, Catherine M.; Golledge, Jonathan

    2016-01-01

    Angiogenesis and inflammation are implicated in aortic aneurysm and atherosclerosis and regulated by angiopoietin-2 (Angpt2). The effect of Angpt2 administration on experimental aortic aneurysm and atherosclerosis was examined. Six-month-old male apolipoprotein E deficient (ApoE−/−) mice were infused with angiotensin II (AngII) and administered subcutaneous human Fc-protein (control) or recombinant Angpt2 (rAngpt2) over 14 days. Administration of rAngpt2 significantly inhibited AngII-induced aortic dilatation and rupture of the suprarenal aorta (SRA), and development of atherosclerosis within the aortic arch. These effects were blood pressure and plasma lipoprotein independent and associated with Tie2 activation and down-regulation of monocyte chemotactic protein-1 (MCP-1) within the SRA. Plasma concentrations of MCP-1 and interleukin-6 were significantly lower in mice receiving rAngpt2. Immunostaining for the monocyte/macrophage marker MOMA-2 and the angiogenesis marker CD31 within the SRA were less in mice receiving rAngpt2 than controls. The percentage of inflammatory (Ly6Chi) monocytes within the bone marrow was increased while that in peripheral blood was decreased by rAngpt2 administration. In conclusion, administration of rAngpt2 attenuated angiotensin II-induced aortic aneurysm and atherosclerosis in ApoE−/− mice associated with reduced aortic inflammation and angiogenesis. Up-regulation of Angpt2 may have potential therapeutic value in patients with aortic aneurysm and atherosclerosis. PMID:27767064

  20. Characterization of Small Focal Renal Lesions: Diagnostic Accuracy with Single-Phase Contrast-enhanced Dual-Energy CT with Material Attenuation Analysis Compared with Conventional Attenuation Measurements.

    PubMed

    Marin, Daniele; Davis, Drew; Roy Choudhury, Kingshuk; Patel, Bhavik; Gupta, Rajan T; Mileto, Achille; Nelson, Rendon C

    2017-03-28

    Purpose To determine whether single-phase contrast material-enhanced dual-energy material attenuation analysis improves the characterization of small (1-4 cm) renal lesions compared with conventional attenuation measurements by using histopathologic analysis and follow-up imaging as the clinical reference standards. Materials and Methods In this retrospective, HIPAA-compliant, institutional review board-approved study, 136 consecutive patients (95 men and 41 women; mean age, 54 years) with 144 renal lesions (111 benign, 33 malignant) measuring 1-4 cm underwent single-energy unenhanced and contrast-enhanced dual-energy computed tomography (CT) of the abdomen. For each renal lesion, attenuation measurements were obtained; attenuation change of greater than or equal to 15 HU was considered evidence of enhancement. Dual-energy attenuation measurements were also obtained by using iodine-water, water-iodine, calcium-water, and water-calcium material basis pairs. Mean lesion attenuation values and material densities were compared between benign and malignant renal lesions by using the two-sample t test. Diagnostic accuracy of attenuation measurements and dual-energy material densities was assessed and validated by using 10-fold cross-validation to limit the effect of optimistic bias. Results By using cross-validated optimal thresholds at 100% sensitivity, iodine-water material attenuation images significantly improved specificity for differentiating between benign and malignant renal lesions compared with conventional enhancement measurements (93% [103 of 111]; 95% confidence interval: 86%, 97%; vs 81% [90 of 111]; 95% confidence interval: 73%, 88%) (P = .02). Sensitivity with iodine-water and calcium-water material attenuation images was also higher than that with conventional enhancement measurements, although the difference was not statistically significant. Conclusion Contrast-enhanced dual-energy CT with material attenuation analysis improves specificity for

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

    NASA Astrophysics Data System (ADS)

    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.

  2. ENHANCEMENTS TO NATURAL ATTENUATION: SELECTED CASE STUDIES

    SciTech Connect

    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).

  3. Grape Seed Extract Attenuates Hepatitis C Virus Replication and Virus-Induced Inflammation

    PubMed Central

    Chen, Wei-Chun; Tseng, Chin-Kai; Chen, Bing-Hung; Lin, Chun-Kuang; Lee, Jin-Ching

    2016-01-01

    Hepatitis C virus (HCV) infection is a causative factor leading to hepatocellular carcinoma due to chronic inflammation and cirrhosis. The aim of the study was first to explore the effects of grape seed extract (GSE) in HCV replication, and then to study mechanisms. The results indicated that a GSE treatment showed significant anti-HCV activity and suppressed HCV-elevated cyclooxygenase-2 (COX-2) expression. In contrast, exogenous COX-2 expression gradually attenuated antiviral effects of GSE, suggesting that GSE inhibited HCV replication by suppressing an aberrant COX-2 expression caused by HCV, which was correlated with the inactivation of IKK-regulated NF-κB and MAPK/ERK/JNK signaling pathways. In addition, GSE also attenuated HCV-induced inflammatory cytokine gene expression. Notably, a combined administration of GSE with interferon or other FDA-approved antiviral drugs revealed a synergistic anti-HCV effect. Collectively, these findings demonstrate the possibility of developing GSE as a dietary supplement to treat patients with a chronic HCV infection. PMID:28066241

  4. A Metabolically-Stabilized Phosphonate Analog of Lysophosphatidic Acid Attenuates Collagen-Induced Arthritis

    PubMed Central

    Sevastou, Ioanna; Sirioti, Ivi; Samiotaki, Martina; Madan, Damian; Prestwich, Glenn D.; Aidinis, Vassilis

    2013-01-01

    Rheumatoid arthritis (RA) is a destructive arthropathy with systemic manifestations, characterized by chronic synovial inflammation. Under the influence of the pro-inflammatory milieu synovial fibroblasts (SFs), the main effector cells in disease pathogenesis become activated and hyperplastic while releasing a number of signals that include pro-inflammatory factors and tissue remodeling enzymes. Activated RA SFs in mouse or human arthritic joints express significant quantities of autotaxin (ATX), a lysophospholipase D responsible for the majority of lysophosphatidic acid (LPA) production in the serum and inflamed sites. Conditional genetic ablation of ATX from SFs resulted in attenuation of disease symptoms in animal models, an effect attributed to diminished LPA signaling in the synovium, shown to activate SF effector functions. Here we show that administration of 1-bromo-3(S)-hydroxy-4-(palmitoyloxy)butyl-phosphonate (BrP-LPA), a metabolically stabilized analog of LPA and a dual function inhibitor of ATX and pan-antagonist of LPA receptors, attenuates collagen induced arthritis (CIA) development, thus validating the ATX/LPA axis as a novel therapeutic target in RA. PMID:23923032

  5. Pretreatment or Posttreatment with Aripiprazole Attenuates Methamphetamine-induced Stereotyped Behavior in Mice

    PubMed Central

    Kitanaka, Nobue; Kitanaka, Junichi; Hall, F. Scott; Kayama, Masaru; Sugimori, Hironobu; Uhl, George R.; Takemura, Motohiko

    2015-01-01

    Aripiprazole is a third-generation atypical antipsychotic and a dopamine D2 receptor partial agonist. In the present study, we investigated whether a single administration of aripiprazole to mice, either as a pretreatment or as a posttreatment, would affect stereotypy induced by methamphetamine (METH). Pretreatment of male ICR mice with aripiprazole (1 or 10 mg/kg, i.p.) attenuated the incidence of METH-induced stereotypical behavior in a dose-dependent manner. Pretreatment of mice with 1 mg/kg aripiprazole produced an increase in the locomotor activity in mice treated with METH compared with mice treated with vehicle plus METH and with 10 mg/kg aripiprazole plus METH. This increase in locomotion is indicative of a rightward shift in the dose–response curve for METH, consistent with a shift in the type of stereotypical behavior observed from biting to sniffing. Aripiprazole posttreatment, after METH-induced stereotypical behavior, was fully expressed and also significantly attenuated overall stereotypy in an aripiprazole dose-dependent manner. These data suggest that the antagonism of METH effects by aripiprazole should be investigated as a potential treatment for acute METH overdose. PMID:26525833

  6. Chlorine signal attenuation in concrete.

    PubMed

    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.

  7. Ultrasound fields in attenuating media.

    PubMed

    Lerch, R; Friedrich, W

    1986-10-01

    For medical ultrasonic imaging and for nondestructive testing, the attenuation of pressure waves and the resulting shift in wave velocity are important features in commonly used transmission media such as biological tissue. An algorithm for the numerical evaluation of pressure field distributions generated by ultrasonic transducers is presented. The attenuation and dispersion of the sound transmission medium are taken into consideration. The sound fields are computed numerically for continuous wave as well as pulse excitation. The transducer has plane or gently curved geometry and is embedded in a plane rigid baffle. The numerically determined pressure fields are presented as 3D plots, as gray-scale images for a fixed time stamp (like a snapshot), or as isobars regarding the maximum values over time for each local point in the area under investigation. The algorithm described here can be utilized as a tool for design of ultrasound transducers, especially array antennas.

  8. Patient position alters attenuation effects in multipinhole cardiac SPECT

    SciTech Connect

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

    2015-03-15

    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

  9. In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry

    SciTech Connect

    Weaver, John; Yang, Yirong; Purvis, Rebecca; Weatherwax, Theodore; Rosen, Gerald M.; Liu, Ke Jian

    2014-03-01

    Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O{sub 2} may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O{sub 2} is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO{sub 2}in vivo remains largely uncharacterized. This study investigated striatal tissue pO{sub 2} changes in male C57BL/6 mice (16–20 g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO{sub 2}in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO{sub 2} was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO{sub 2} to 64%. More importantly, pO{sub 2} did not recover fully to control levels even 24 h after administration of a single dose of METH and continual exposure to METH exacerbates the condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO{sub 2} indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO{sub 2}, which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults. - Highlights: • Explored striatal tissue pO{sub 2}in vivo after METH administration by EPR oximetry. • pO{sub 2} was reduced by 81% after a single dose and 64% after 3 consecutive daily doses. • pO{sub 2} did not recover fully to control levels even 24 h after a single dose. • Decrease in brain tissue pO{sub 2} may be associated with a decrease in

  10. Attenuation Correction for MR Coils in Combined PET/MR Imaging: A Review

    PubMed Central

    Eldib, Mootaz; Bini, Jason; Faul, David D.; Oesingmann, Niels; Tsoumpas, Charalampos; Fayad, Zahi A.

    2015-01-01

    Synopsis With the introduction of clinical PET/MR systems, novel attenuation correction methods are needed, as there are no direct or indirect MR methods to measure the attenuation of the objects in the FOV. A unique challenge for PET/MR attenuation correction is that coils for MR data acquisition are located in the FOV of the PET detector and could induce significant quantitative errors. In this review, we summarize and evaluate current methods and techniques to correct for the attenuation of a variety of coils. PMID:26952728

  11. Influence of attenuation on acoustic emission signals in carbon fiber reinforced polymer panels.

    PubMed

    Asamene, Kassahun; Hudson, Larry; Sundaresan, Mannur

    2015-05-01

    Influence of attenuation on acoustic emission (AE) signals in Carbon Fiber Reinforced Polymer (CFRP) crossply and quasi-isotropic panels is examined in this paper. Attenuation coefficients of the fundamental antisymmetric (A0) and symmetric (S0) wave modes were determined experimentally along different directions for the two types of CFRP panels. In the frequency range from 100 kHz to 500 kHz, the A0 mode undergoes significantly greater changes due to material related attenuation compared to the S0 mode. Moderate to strong changes in the attenuation levels were noted with propagation directions. Such mode and frequency dependent attenuation introduces major changes in the characteristics of AE signals depending on the position of the AE sensor relative to the source. Results from finite element simulations of a microscopic damage event in the composite laminates are used to illustrate attenuation related changes in modal and frequency components of AE signals.

  12. Attenuation by creatine of myocardial metabolic stress in Brattleboro rats caused by chronic inhibition of nitric oxide synthase.

    PubMed Central

    Constantin-Teodosiu, D.; Greenhaff, P. L.; Gardiner, S. M.; Randall, M. D.; March, J. E.; Bennett, T.

    1995-01-01

    1. The present experiment was undertaken to investigate: (a) the effect of nitric oxide synthase (NOS) inhibition, mediated by oral supplementation of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on measures of myocardial energy metabolism and function: (b) the effect of oral creatine supplementation on these variables, in the absence and presence of L-NAME. 2. In one series of experiments, 4 weeks oral administration of L-NAME (0.05 mg ml-1 day-1 in the drinking water) to Brattleboro rats caused significant reductions in myocardial ATP, creatine, and total creatine concentrations and an accumulation of tissue lactate when compared with control animals. Administration of creatine (0.63 mg ml-1 day-1 in the drinking water) for 4 weeks elevated myocardial creatine and total creatine concentrations and reduced lactate accumulation, but did not significantly affect ATP or phosphocreatine (PCr). Concurrent treatment with creatine and L-NAME prevented the reduction in creatine and total creatine concentrations, and significantly attenuated the accumulation of lactate and the reduction in ATP seen with L-NAME alone. 3. In a second series of experiments, 4 weeks treatment with L-NAME and creatine plus L-NAME increased mean arterial blood pressure in conscious Brattleboro rats. Hearts isolated from these animals showed decreased coronary flow and left ventricular developed pressure (LVDP), and total mechanical performance. Treatment with creatine alone had no measurable effect on either mean arterial blood pressure or coronary flow in isolated hearts. However, there was an increase in LVDP, but not in total mechanical performance, because there was a bradycardia. 4. These results indicate that creatine supplementation can attenuate the metabolic stress associated with L-NAME administration and that this effect occurs as a consequence of the action of creatine on myocardial energy metabolism. PMID:8719809

  13. Mapping Lateral Pn Attenuation Variation in Asia

    NASA Astrophysics Data System (ADS)

    Yang, X.; Phillips, W. S.; Randall, G. E.

    2009-12-01

    Pn travels most of its path in the uppermost mantle. Mapping of the lateral variation of Pn amplitude attenuation may shed light on the physical and chemical state, and dynamics of the upper mantle. In addition to material attenuation, Pn amplitudes are affected by other factors including the spherical shape of the Earth and Moho topography. In order to derive reliable Pn attenuation, we adopt a frequency-dependent Pn geometric-spreading model, which was designed to account for the effect of the Earth’s sphericity, to correct Pn amplitudes in preparation for attenuation estimation. We obtain physically reasonable attenuation estimates from Pn amplitudes corrected using the new spreading model. Pn amplitudes corrected using the traditional frequency-independent power-law spreading model, on the other hand, yield attenuation estimates that are either too large or negative. Using properly geometric-spreading corrected Pn amplitudes, we conducted attenuation tomography and developed 2D Pn attenuation models at multiple frequencies from 0.5 Hz to 8 Hz for Asia. Overall Pn attenuation patterns correlate, to some degree, with our current knowledge of the state of the upper mantle of the region. We see consistent low attenuation in cratonic regions and high attenuation along the western Pacific Ocean. The attenuation pattern in the Tibetan Plateau region seems to be frequency dependent with high attenuation around 1 Hz and low attenuation at 8 Hz. Application of the attenuation model to the nuclear-explosion discrimination problem leads to appreciable improvements of the discriminant compared with currently adopted method.

  14. Polyphenolic Extract of Euphorbia supina Attenuates Manganese-Induced Neurotoxicity by Enhancing Antioxidant Activity through Regulation of ER Stress and ER Stress-Mediated Apoptosis

    PubMed Central

    Bahar, Entaz; Lee, Geum-Hwa; Bhattarai, Kashi Raj; Lee, Hwa-Young; Choi, Min-Kyung; Rashid, Harun-Or; Kim, Ji-Ye; Chae, Han-Jung; Yoon, Hyonok

    2017-01-01

    Manganese (Mn) is an important trace element present in human body, which acts as an enzyme co-factor or activator in various metabolic reactions. While essential in trace amounts, excess levels of Mn in human brain can produce neurotoxicity, including idiopathic Parkinson’s disease (PD)-like extrapyramidal manganism symptoms. This study aimed to investigate the protective role of polyphenolic extract of Euphorbia supina (PPEES) on Mn-induced neurotoxicity and the underlying mechanism in human neuroblastoma SKNMC cells and Sprague-Dawley (SD) male rat brain. PPEES possessed significant amount of total phenolic and flavonoid contents. PPEES also showed significant antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and reducing power capacity (RPC) assays. Our results showed that Mn treatment significantly reduced cell viability and increased lactate dehydrogenase (LDH) level, which was attenuated by PPEES pretreatment at 100 and 200 µg/mL. Additionally, PPEES pretreatment markedly attenuated Mn-induced antioxidant status alteration by resolving the ROS, MDA and GSH levels and SOD and CAT activities. PPEES pretreatment also significantly attenuated Mn-induced mitochondrial membrane potential (ΔΨm) and apoptosis. Meanwhile, PPEES pretreatment significantly reversed the Mn-induced alteration in the GRP78, GADD34, XBP-1, CHOP, Bcl-2, Bax and caspase-3 activities. Furthermore, administration of PPEES (100 and 200 mg/kg) to Mn exposed rats showed improvement of histopathological alteration in comparison to Mn-treated rats. Moreover, administration of PPEES to Mn exposed rats showed significant reduction of 8-OHdG and Bax immunoreactivity. The results suggest that PPEES treatment reduces Mn-induced oxidative stress and neuronal cell loss in SKNMC cells and in the rat brain. Therefore, PPEES may be considered as potential treat-ment in Mn-intoxicated patients. PMID:28146110

  15. Promises and pitfalls of live attenuated pneumococcal vaccines.

    PubMed

    Rosch, Jason W

    2014-01-01

    The pneumococcus is a remarkably adaptable pathogen whose disease manifestations range from mucosal surface infections such as acute otitis media and pneumonia to invasive infections such as sepsis and meningitis. Currently approved vaccines target the polysaccharide capsule, of which there are over 90 distinct serotypes, leading to rapid serotype replacement in vaccinated populations. Substantial progress has been made in the development of a universal pneumococcal vaccine, with efforts focused on broadly conserved and protective protein antigens. An area attracting considerable attention is the potential application of live attenuated vaccines to confer serotype-independent protection against mucosal and systemic infection. On the basis of recent work to understand the mucosal and systemic responses to nasal administration of pneumococci and to develop novel attenuation strategies, the prospect of a practical and protective live vaccine remains promising.

  16. The sesame lignan sesamin attenuates vascular dysfunction in streptozotocin diabetic rats: involvement of nitric oxide and oxidative stress.

    PubMed

    Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad; Jalali Nadoushan, Mohammad-Reza; Vaez Mahdavi, Mohammad-Reza; Kalalian-Moghaddam, Hamid; Roghani-Dehkordi, Farshad; Dariani, Sharareh; Raoufi, Safoura

    2013-01-05

    The effect of chronic administration of sesamin was studied on aortic reactivity of streptozotocin diabetic rats. Male diabetic rats received sesamin for 7 weeks after diabetes induction. Contractile responses to KCl and phenylephrine and relaxation response to acetylcholine were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to phenylephrine was significantly lower in sesamin-treated diabetic rats relative to untreated diabetics and endothelium removal abolished this difference. Meanwhile, endothelium-dependent relaxation to acetylcholine was significantly higher in sesamin-treated diabetic rats as compared to diabetic ones and pretreatment of rings with nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester significantly attenuated the observed response. Two-month diabetes also resulted in an elevation of malondialdehyde and decreased superoxide dismutase activity and sesamin treatment significantly improved these changes. Therefore, chronic treatment of diabetic rats with sesamin could prevent some abnormal changes in vascular reactivity in diabetic rats through nitric oxide and via attenuation of oxidative stress and tissue integrity of endothelium is necessary for its beneficial effect.

  17. Attenuating effect of bromocriptine on cysteamine anticarcinogenesis of stomach cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine

    SciTech Connect

    Tatsuta, M.; Iishi, H.; Baba, M.; Ichii, M.; Nakaizumi, A.; Uehara, H.; Taniguchi, H. )

    1990-09-01

    The effect of bromocriptine on inhibition by cysteamine of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine was investigated in inbred Wistar rats. After 25 weeks of p.o. treatment with N-methyl-N'-nitro-N-nitrosoguanidine, rats were given injections every other day: cysteamine (50 mg/kg body weight); cysteamine (50 mg/kg body weight) plus bromocriptine (0.5 or 0.25 mg/kg body weight); or bromocriptine (0.5 or 0.25 mg/kg body weight). In week 52, the group treated with cysteamine showed a significantly decreased incidence of gastric cancers. Concomitant treatment with bromocriptine at 0.5 but not at 0.25 mg/kg body weight significantly attenuated the inhibitory effect of cysteamine on gastric carcinogenesis. Administration of bromocriptine alone at either dosage had no influence on gastric carcinogenesis. The labeling index of the antral mucosa was significantly reduced in rats treated with cysteamine and significantly higher in those treated concomitantly with bromocriptine at 0.5 mg/kg body weight than in those treated with cysteamine alone. These findings indicate that cysteamine suppressed gastric carcinogenesis and that bromocriptine at high dosage attenuated this inhibition. These findings also suggest that dopamine is involved in the mechanism of inhibition of gastric carcinogenesis by cysteamine.

  18. Attenuation of morphine tolerance by minocycline and pentoxifylline in naive and neuropathic mice.

    PubMed

    Mika, Joanna; Wawrzczak-Bargiela, Agnieszka; Osikowicz, Maria; Makuch, Wioletta; Przewlocka, Barbara

    2009-01-01

    We have previously demonstrated that glial inhibitors reduce the development of allodynia and hyperalgesia, potentiating the effect of a single morphine dose in a neuropathic pain model. This study explores the effects of two glial activation inhibitors, minocycline and pentoxifylline, on the development of tolerance to morphine in naive and chronic constriction injury (CCI)-exposed mice. Administration of morphine to naive (20 mg/kg; i.p.) and CCI-exposed mice (40 mg/kg; i.p.) twice daily resulted in tolerance to its anti-nociceptive effect after 6 days. Injections of morphine were combined with minocycline (30 mg/kg, i.p.) or pentoxifylline (20 mg/kg, i.p.) administered as two preemptive doses before first morphine administration in naive or pre-injury in CCI-exposed mice, and repeated twice daily 30 min before each morphine administration. With treatment, development of morphine tolerance was delayed by 5 days (from 6 to 11 days), as measured by the tail-flick test in naive and by tail-flick, von Frey, and cold plate tests in CCI-exposed mice. Western blot analysis of CD11b/c and GFAP protein demonstrated that minocycline and pentoxifylline, at doses delaying development of tolerance to morphine analgesia, significantly diminished the morphine-induced increase in CD11b/c protein level. We found that repeated systemic administration of glial inhibitors significantly delays development of morphine tolerance by attenuating the level of this microglial marker under normal and neuropathic pain conditions. Our results support the idea that targeting microglial activation during morphine therapy/treatment is a novel and clinically promising method for enhancing morphine's analgesic effects, especially in neuropathic pain.

  19. Dexamethasone loaded nanoparticles exert protective effects against Cisplatin-induced hearing loss by systemic administration.

    PubMed

    Sun, Changling; Wang, Xueling; Chen, Dongye; Lin, Xin; Yu, Dehong; Wu, Hao

    2016-04-21

    Ototoxicity is one of the most important adverse effects of cisplatin chemotherapy. As a common treatment of acute sensorineural hearing loss, systemic administration of steroids was demonstrated ineffective against cisplatin-induced hearing loss (CIHL) in published studies. The current study aimed to evaluate the potential protective effect of dexamethasone (DEX) encapsulated in polyethyleneglycol-coated polylactic acid (PEG-PLA) nanoparticles (DEX-NPs) against cisplatin-induced hearing loss following systemic administration. DEX was fabricated into PEG-PLA nanoparticles using emulsion and evaporation technique as previously reported. DEX or DEX-NPs was administered intraperitoneally to guinea pigs 1h before cisplatin administration. Auditory brainstem response (ABR) threshold shifts were measured at four frequencies (4, 8, 16, and 24kHz) 1 day before and three days after cisplatin injection. Cochlear morphology was examined to evaluate inner ear injury induced by cisplatin exposure. A single dose of DEX-NPs 1h before cisplatin treatment resulted in a significant preservation of the functional and structural properties of the cochlea, which was equivalent to the effect of multidose (3 days) DEX injection. In contrast, no significant protective effect was observed by single dose injection of DEX. The results of histological examination of the cochleae were consistent with the functional measurements. In conclusion, a single dose DEX-NPs significantly attenuated cisplatin ototoxicity in guinea pigs after systemic administration at both histological and functional levels indicating the potential therapeutic benefits of these nanoparticles for enhancing the delivery of DEX in acute sensorineural hearing loss.

  20. Immune responses to a recombinant attenuated Salmonella typhimurium strain expressing a Taenia solium oncosphere antigen TSOL18.

    PubMed

    Ding, Juntao; Zheng, Yadong; Wang, Ying; Dou, Yongxi; Chen, Xiaoyu; Zhu, Xueliang; Wang, Shuai; Zhang, Shaohua; Liu, Zhenyong; Hou, Junling; Zhai, Junjun; Yan, Hongbin; Luo, Xuenong; Cai, Xuepeng

    2013-01-01

    A tapeworm, Taenia solium, remains a great threat to human health, particularly in developing countries. The life cycle of T. solium is thought to be terminated via vaccination of intermediate hosts. In this study, we constructed a recombinant attenuated Salmonella typhimurium live vaccine strain χ4558 expressing a TSOL18 antigen. SDS-PAGE and Western blot confirmed the expression of the interest protein and its antigenic property. The recombinant strain stably propagated in vitro, of which the growth was not reversely influenced by TSOL18 protein expressed. It was also shown that mice survived 10(12) CFU of S. typhimurium χ4558, while all mice infected with 10(7) CFU of the wild-type died within five days. The mouse experiment indicated that vaccine strain χ4558 induced a high titer of specific antibody for a long time. In contrast to the controls, the vaccinated mice had an obvious augment of CD4(+) and CD8(+) T lymphocytes and the percentage of helper CD4(+)/CD8(+) T lymphocytes was significantly increased (p<0.01). After oral administration, S. typhimurium χ4558 was first colonized mainly in the Peyer's patches and then predominantly in the mesenteric lymph nodes and spleens in the vaccinated mice. In addition, the high levels of specific anti-TSOL18 antibodies were also observed in pigs administrated with S. typhimurium χ4558. Collectively, these results demonstrate the possibility of use of an attenuated S. typhimurium strain as a vector to deliver protective antigens of T. solium.

  1. Paine Appointed Administrator

    NASA Technical Reports Server (NTRS)

    1969-01-01

    President Richard M. Nixon announcing the appointment of Dr. Thomas O. Paine as Administrator for the National Aeronautics and Space Administration. The ceremony was held at the White House. Paine had been serving as acting administrator. From left to right: President Richard M. Nixon NASA Administrator Dr. Thomas O. Paine Vice President Spiro T. Agnew

  2. Vinpocetine attenuates lipid accumulation and atherosclerosis formation

    SciTech Connect

    Cai, Yujun; Li, Jian-Dong; Yan, Chen

    2013-05-10

    Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.

  3. The effects of acoustic attenuation in optoacoustic signals.

    PubMed

    Deán-Ben, X Luís; Razansky, Daniel; Ntziachristos, Vasilis

    2011-09-21

    In this paper, it is demonstrated that the effects of acoustic attenuation may play a significant role in establishing the quality of tomographic optoacoustic reconstructions. Accordingly, spatially dependent reduction of signal amplitude leads to quantification errors in the reconstructed distribution of the optical absorption coefficient while signal broadening causes loss of image resolution. Here we propose a correction algorithm for accounting for attenuation effects, which is applicable in both the time and frequency domains. It is further investigated which part of the optoacoustic signal spectrum is practically affected by those effects in realistic imaging scenarios. The validity and benefits of the suggested modelling and correction approaches are experimentally validated in phantom measurements.

  4. Development of live attenuated Streptococcus agalactiae vaccine for tilapia via continuous passage in vitro.

    PubMed

    Li, L P; Wang, R; Liang, W W; Huang, T; Huang, Y; Luo, F G; Lei, A Y; Chen, M; Gan, X

    2015-08-01

    Fish Streptococcus agalactiae (S. agalactiae) seriously harms the world's aquaculture industry and causes huge economic losses. This study aimed to develop a potential live attenuated vaccine of S. agalactiae. Pre-screened vaccine candidate strain S. agalactiae HN016 was used as starting material to generate an attenuated strain S. agalactiae YM001 by continuous passage in vitro. The biological characteristics, virulence, and stability of YM001 were detected, and the protective efficacy of YM001 immunization in tilapia was also determined. Our results indicated that the growth, staining, characteristics of pulsed-field gel electrophoresis (PFGE) genotype, and virulence of YM001 were changed significantly as compared to the parental strain HN016. High doses of YM001 by intraperitoneal (IP) injection (1.0 × 10(9) CFU/fish) and oral gavage (1.0 × 10(10) CFU/fish) respectively did not cause any mortality and morbidity in tilapia. The relative percent survivals (RPSs) of fishes immunized with YM001 (1.0 × 10(8) CFU/fish, one time) via injection, immersion, and oral administration were 96.88, 67.22, and 71.81%, respectively, at 15 days, and 93.61, 60.56, and 53.16%, respectively, at 30 days. In all tests with 1-3 times of immunization in tilapia, the dosages at 1 × 10(8) and 1 × 10(9) CFU/fish displayed the similar best results, whereas the immunoprotection of the dosages at 1 × 10(6) and 1 × 10(7) CFU/fish declined significantly (P < 0.01), and 1 × 10(5) CFU/fish hardly displayed any protective effect. In addition, the efficacy of 2-3 times of immunization was significantly higher than that of single immunization (P < 0.01) while no significant difference in the efficacy between twice and thrice of immunization was seen (P > 0.05). The level of protective antibody elicited by oral immunization was significantly higher compared to that of the control group (P < 0.01), and the antibody reached their maximum levels 14-21 days after the immunization but decreased

  5. Antagonism of metabotropic glutamate 1 receptors attenuates behavioral effects of cocaine and methamphetamine in squirrel monkeys.

    PubMed

    Achat-Mendes, Cindy; Platt, Donna M; Spealman, Roger D

    2012-10-01

    Within the group I family of metabotropic glutamate receptors (mGluRs), substantial evidence points to a role for mGluR5 mechanisms in cocaine's abuse-related behavioral effects, but less is understood about the contribution of mGluR1, which also belongs to the group I mGluR family. The selective mGluR1 antagonist JNJ16259685 [(3,4-dihydro-2H-pyrano-[2,3-b]quinolin-7-yl)-(cis-4-methoxycyclohexyl)-methanone] was used to investigate the role of mGluR1 in the behavioral effects of cocaine and methamphetamine. In drug discrimination experiments, squirrel monkeys were trained to discriminate cocaine from saline by using a two-lever, food-reinforced operant procedure. JNJ16259685 (0.56 mg/kg) pretreatments significantly attenuated cocaine's discriminative stimulus effects and the cocaine-like discriminative stimulus effects of methamphetamine. In monkeys trained to self-administer cocaine or methamphetamine under a second-order schedule of intravenous drug injection, JNJ16259685 (0.56 mg/kg) significantly reduced drug-reinforced responding, resulting in a downward displacement of dose-response functions. In reinstatement studies, intravenous priming with cocaine accompanied by restoration of a cocaine-paired stimulus reinstated extinguished cocaine-seeking behavior, which was significantly attenuated by JNJ16259685 (0.56 mg/kg). Finally, in experiments involving food rather than drug self-administration, cocaine and methamphetamine increased the rate of responding, and the rate-increasing effects of both psychostimulants were significantly attenuated by JNJ16259685 (0.3 mg/kg). At the doses tested, JNJ16259685 did not significantly suppress food-reinforced behavior (drug discrimination or fixed-interval schedule of food delivery), but did significantly reduce species-typical locomotor activity in observational studies. To the extent that the psychostimulant-antagonist effects of JNJ16259685 are independent of motor function suppression, further research is warranted to

  6. Beneficial effect of zinc chloride and zinc ionophore pyrithione on attenuated cardioprotective potential of preconditioning phenomenon in STZ-induced diabetic rat heart.

    PubMed

    Jamwal, Sumit; Kumar, Kushal; Reddy, B V Krishna

    2016-05-01

    Ischemic preconditioning (IPC) is well demonstrated to produce cardioprotection by phosphorylation and subsequent inactivation of glycogen synthase kinase-3β (GSk-3β) in the normal rat heart, but its effect is attenuated in the diabetic rat heart. This study was designed to investigate the effect of zinc chloride and zinc ionophore pyrithione (ZIP) on the attenuated cardioprotective potential of IPC in the diabetic rat heart. Diabetes mellitus (DM) was induced by a single intraperitoneal administration of streptozotocin (STZ) (50 mg/kg; i.p). The isolated perfused rat heart was subjected to 30 minutes of ischemia followed by 120 minutes of reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining and cardiac injury was measured by estimating lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in the coronary effluent. Also, GSK-3β was measured and neutrophil accumulation was measured by estimating myeloperoxidase (MPO) levels. IPC significantly decreased the myocardial infarct size, the release of LDH and CK-MB, the GSK-3β levels and the MPO levels in the normal rat heart. Pre- and post-ischemic treatment with zinc chloride and zinc ionophore pyrithione (ZIP) in the normal and diabetic rat hearts significantly decreased the myocardial infarct size, the level of CK-MB and LDH in the coronary effluent and GSK-3β and MPO levels. Our results suggest that pharmacological preconditioning with zinc chloride and ZIP significantly restored the attenuated cardioprotective potential of IPC in the diabetic rat heart.

  7. Red Palm Oil Attenuates Lead Acetate Induced Testicular Damage in Adult Male Sprague-Dawley Rats.

    PubMed

    Jegede, A I; Offor, U; Azu, O O; Akinloye, O

    2015-01-01

    To study the protective effect of Red Palm Oil (RPO) on testicular damage induced by administration of lead acetate on male Sprague-Dawley rats, 28 rats divided into four groups of 7 animals each were used. They were administered orally with RPO (1 mL and 2 mL) and lead acetate (i.p.) 6 mg/kg body weight/day, respectively. Treatment was conducted for 8 weeks, and 24 hrs after the last treatment the rats were sacrificed using cervical dislocation. Sperms collected from epididymis were used for seminal fluid analyses; while the testes sample was used for ROS and oxidative enzyme activities assessment. Statistical analysis was carried out using GraphPad Prism 5.02 statistical analysis package. Administration of lead acetate increased generation of reactive oxygen species (ROS) significantly (p < 0.05) as evidenced by the elevated value of H2O2 and LPO and decreased GSH level. Also there was reduced epididymal sperm count, poor grade of sperm motility, and lower percentage of normal sperm morphology significantly. Coadministration with RPO, however, has a protective effect against lead toxicity by decreasing H2O2 production, increased GSH level, and increased sperm qualities especially. This shows that RPO has a potential to attenuate the toxic effect of lead on testicular cells preventing possible resultant male infertility.

  8. Red Palm Oil Attenuates Lead Acetate Induced Testicular Damage in Adult Male Sprague-Dawley Rats

    PubMed Central

    Jegede, A. I.; Offor, U.; Azu, O. O.; Akinloye, O.

    2015-01-01

    To study the protective effect of Red Palm Oil (RPO) on testicular damage induced by administration of lead acetate on male Sprague-Dawley rats, 28 rats divided into four groups of 7 animals each were used. They were administered orally with RPO (1 mL and 2 mL) and lead acetate (i.p.) 6 mg/kg body weight/day, respectively. Treatment was conducted for 8 weeks, and 24 hrs after the last treatment the rats were sacrificed using cervical dislocation. Sperms collected from epididymis were used for seminal fluid analyses; while the testes sample was used for ROS and oxidative enzyme activities assessment. Statistical analysis was carried out using GraphPad Prism 5.02 statistical analysis package. Administration of lead acetate increased generation of reactive oxygen species (ROS) significantly (p < 0.05) as evidenced by the elevated value of H2O2 and LPO and decreased GSH level. Also there was reduced epididymal sperm count, poor grade of sperm motility, and lower percentage of normal sperm morphology significantly. Coadministration with RPO, however, has a protective effect against lead toxicity by decreasing H2O2 production, increased GSH level, and increased sperm qualities especially. This shows that RPO has a potential to attenuate the toxic effect of lead on testicular cells preventing possible resultant male infertility. PMID:26516332

  9. Captopril and telmisartan treatments attenuate cadmium-induced testicular toxicity in rats.

    PubMed

    Fouad, Amr A; Jresat, Iyad

    2013-04-01

    The possible protective effect of captopril, an angiotensin-converting enzyme inhibitor, vs. telmisartan, an angiotensin II-receptor antagonist, was investigated in rats with testicular injury induced by a single i.p. injection of cadmium chloride (2 mg/kg). Captopril (60 mg/kg/day, p.o.) and telmisartan (10 mg/kg/day, p.o.) were given for five consecutive days, starting 3 days before cadmium administration. Both agents significantly increased serum testosterone level, which was reduced by cadmium, suppressed lipid peroxidation, restored the depleted reduced glutathione, decreased the elevations of nitric oxide, tumor necrosis factor-α, and cadmium ion levels, and attenuated the reductions of selenium and zinc ions in testicular tissue resulted from cadmium administration. Immunohistochemical analysis revealed that both captopril and telmisartan significantly reduced the cadmium-induced expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand, and caspase-3 in testicular tissue. The differences between the results obtained with captopril and telmisartan were insignificant, suggesting that both drugs equally protected the testicular tissue from the detrimental effects of cadmium.

  10. Rebamipide attenuates 5-Fluorouracil-induced small intestinal mucositis in a mouse model.

    PubMed

    Kim, Hyun Jin; Kim, Jin Hyun; Moon, Won; Park, Jongha; Park, Seun Ja; Song, Geun Am; Han, Seung Hee; Lee, Jong Hun

    2015-01-01

    5-Fluorouracil (5-FU)-induced intestinal mucositis is one of the most common morbidities in chemotherapy and involves the reactive oxygen species (ROS) system, apoptosis, and inflammatory cytokines. Rebamipide exerts a mucosal-protective effect, mediated through several mechanisms. The aim of this study was to evaluate the effects of rebamipide in 5-FU-induced mouse small-intestinal mucositis. BALB/c mice were assigned randomly to four groups; (1) control group (n=10; receiving saline orally for 6 d), (2) rebamipide group (n=10; 150 mg/kg rebamipide for 6 d orally), (3) 5-FU group (n=10; 30 mg/kg 5-FU for 5 d, intraperitoneally (i.p.)), and (4) rebamipide +5-FU group (n=10; 150 mg/kg rebamipide for 6 d orally and 30 mg/kg 5-FU for 5 d, i.p.). Body weights and diarrhea scales were assessed. At day 5, the mice were sacrificed. Small intestinal tissue was used for: (1) hematoxylin and eosin (HE) staining for determination of small intestinal villi height, (2) terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay, (3) immunohistochemistry for inducible nitric oxide synthase (iNOS), F4/80, and transforming growth factor (TGF)-β1, (4) measurement of serum and tissue GSH levels, and (5) measurement of serum tumor necrosis factor (TNF)-α levels. Rebamipide attenuated the severity of mucosal injury reflected by body weight changes, degrees of diarrhea, and heights of villi. Rebamipide reduced the expression of iNOS and TGF-β1, apoptosis, macrophage accumulation, serum TNF-α levels, and prevented reductions in serum and tissue glutathione (GSH) levels by 5-FU administration. These results suggest that rebamipide promotes several mechanisms of mucosal protection and attenuated the 5-FU-induced mucosal injury. In conclusion, administration of rebamipide may have significant protective effects against 5-FU-induced intestinal mucositis.

  11. TNF-α receptor antagonist attenuates isoflurane-induced cognitive impairment in aged rats

    PubMed Central

    YANG, NENGLI; LIANG, YAFENG; YANG, PEI; WANG, WEIJIAN; ZHANG, XUEZHENG; WANG, JUNLU

    2016-01-01

    Postoperative cognitive dysfunction (POCD), a common clinical in aged patients, is characterized by deficits in cognitive functions in patients following anesthesia and surgery. It has been demonstrated that isoflurane may lead to cognitive impairment in aged rats; however, effective clinical interventions for preventing this disorder are limited. Tumor necrosis factor (TNF)-α has been suggested to be involved in neuroinflammation as well as the development of POCD. Accordingly, the present study aimed to investigate whether TNF-α signaling is involved in the isoflurane-induced cognitive impairment in aged rats, and whether TNF-α receptor antagonist are able to attenuate isoflurane-induced cognitive impairment in aged rats. A population of 20-month-old rats were administered TNF-α receptor antagonist R-7050 or an equal volume of saline by intraperitoneal injection 12 h prior to exposure to isoflurane to model cognitive impairment following anesthesia in old patients. Then the rats were exposed to 1.3% isoflurane for 4 h. In the control group, rats showed impaired cognitive functions evaluated by Morris water maze assay after isoflurane exposure. Furthermore, isoflurane exposure induced marked upregulation of proinflammatory cytokines, including interleukin (IL)-1β, TNF-α, IL-6 and IL-8 in the hippocampus tissue. In the experimental group, intracisternal administration of TNF-α receptor antagonist R-7050 significantly attenuated isoflurane-induced cognitive impairment and upregulation of proinflammatory cytokines. Further investigation revealed that intracisternal administration of TNF-α receptor antagonist R-7050 notably suppressed isoflurane-induced activation of NF-κB and MAPK signaling. Collectively, the present results suggest that TNF-α receptor antagonist may serve as a potential agent for the prevention of anesthesia-induced cognitive decline in aged patients. PMID:27347079

  12. Ontology representation and analysis of vaccine formulation and administration and their effects on vaccine immune responses

    PubMed Central

    2012-01-01

    Background A vaccine is a processed material that if administered, is able to stimulate an adaptive immune response to prevent or ameliorate a disease. A vaccination process may protect the host against subsequent exposure to an infectious agent and result in reduced disease or total prevention of the disease. Vaccine formulation and administration methods may affect vaccine safety and efficacy significantly. Results In this report, the detailed classification and definitions of vaccine components and vaccine administration processes are represented using OWL within the framework of the Vaccine Ontology (VO). Different use cases demonstrate how different vaccine formulations and routes of vaccine administration affect the protection efficacy, general immune responses, and adverse events following vaccination. For example, vaccinations of mice with Brucella abortus vaccine strain RB51 using intraperitoneal or intranasal administration resulted in different protection levels. As shown in the vaccine adverse event data provided by US FDA, live attenuated and nonliving vaccines are usually administered in different routes and have different local and systematic adverse effect manifestations. Conclusions Vaccine formulation and administration route can independently or collaboratively affect host response outcomes (positive protective immunity or adverse events) after vaccination. Ontological representation of different vaccine and vaccination factors in these two areas allows better understanding and analysis of the causal effects between different factors and immune responses. PMID:23256535

  13. N-acetylcysteine attenuates dimethylnitrosamine induced oxidative stress in rats.

    PubMed

    Sathish, Priya; Paramasivan, Vijayalakshmi; Palani, Vivekanandan; Sivanesan, Karthikeyan

    2011-03-05

    Oxidative stress has been implicated in the pathogenesis and progression of various hepatic disorders and hence screening for a good hepatoprotective and antioxidant agent is the need of the hour. The present study was aimed to investigate the hepatoprotective and antioxidant property of N-acetylcysteine (NAC) against dimethylnitrosamine (DMN) induced oxidative stress and hepatocellular damage in male Wistar albino rats. Administration of single dose of DMN (5mg/kg b.w.; i.p.) resulted in significant elevation in the levels of serum aspartate transaminase and alanine transaminase, indicating hepatocellular damage. Oxidative stress induced by DMN treatment was confirmed by an elevation in the status of lipid peroxidation (LPO) and reduction in the activities of enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase and in the levels of non-enzymic antioxidants, reduced glutathione, vitamin-C and vitamin-E in the liver tissue. DMN induced oxidative stress and hepatocellular membrane instability was further substantiated by a decline in the status of the membrane bound ATPases in the liver tissue. Post-treatment with NAC (50mg/kg b.w.; p.o.) for 7days effectively protected against the DMN induced insult to liver by preventing the elevation in the status of the serum marker enzymes and LPO, and restoring the activities of both the enzymic and non-enzymic antioxidants and membrane bound ATPases towards normalcy. These results demonstrate that NAC acts as a good hepatoprotective and antioxidant agent in attenuating DMN induced oxidative stress and hepatocellular damage.

  14. SEISMIC ATTENUATION FOR RESERVOIR CHARACTERIZATION

    SciTech Connect

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

    2003-04-01

    In this report we will show some new Q related seismic attributes on the Burlington-Seitel data set. One example will be called Energy Absorption Attribute (EAA) and is based on a spectral analysis. The EAA algorithm is designed to detect a sudden increase in the rate of exponential decay in the relatively higher frequency portion of the spectrum. In addition we will show results from a hybrid attribute that combines attenuation with relative acoustic impedance to give a better indication of commercial gas saturation.

  15. Resveratrol attenuates acute kidney injury by inhibiting death receptor-mediated apoptotic pathways in a cisplatin-induced rat model

    PubMed Central

    Hao, Qiufa; Xiao, Xiaoyan; Zhen, Junhui; Feng, Jinbo; Song, Chun; Jiang, Bei; Hu, Zhao

    2016-01-01

    Acute kidney injury is a clinical syndrome characterized by a loss of renal function and acute tubular necrosis. Resveratrol exerts a wide range of pharmacological effects based on its anti-inflammatory, antioxidant and cytoprotective properties. The present study aimed to evaluate whether resveratrol attenuates acute kidney injury in a cisplatin-induced rat model and to investigate the potential mechanisms involved. Rats were randomly divided into four treatment groups: Control, cisplatin, resveratrol, and cisplatin plus resveratrol. Rats exposed to cisplatin displayed acute kidney injury, identified by analysis of renal function and histopathological observation. Resveratrol significantly ameliorated the increased serum creatinine, blood urea nitrogen, renal index and histopathological damage induced by cisplatin. Furthermore, compared with untreated control animals, cisplatin lead to significantly increased expression of Fas ligand, tumor necrosis factor-α (TNF-α), caspase-8 and Bcl-2 associated protein X apoptosis regulator (Bax), and decreased expression of anti-apoptosis regulators, BH3 interacting domain death agonist (BID) and B cell lymphoma 2 apoptosis regulator (Bcl-2). Administration of resveratrol significantly reversed the cisplatin-induced alteration in these apoptosis-associated proteins. In conclusion, these findings suggest that resveratrol attenuates cisplatin-induced acute kidney injury through inactivation of the death receptor-mediated apoptotic pathway, and may provide a new therapeutic strategy to ameliorate the process of acute kidney injury. PMID:27600998

  16. Cannabinoid CB2 receptor stimulation attenuates brain edema and neurological deficits in a germinal matrix hemorrhage rat model.

    PubMed

    Tao, Yihao; Tang, Jun; Chen, Qianwei; Guo, Jing; Li, Lin; Yang, Liming; Feng, Hua; Zhu, Gang; Chen, Zhi

    2015-03-30

    Germinal matrix hemorrhage (GMH) is one of the most common and devastating cerebrovascular events that affect premature infants, resulting in a significant socioeconomic burden. However, GMH has been largely unpreventable, and clinical treatments are mostly inadequate. In the present study, we tested the hypothesis that JWH133, a selective CB2 receptor agonist, could attenuate brain injury and neurological deficits in a clostridial collagenase VII induced GMH model in seven-day-old (P7) S-D rat pups. Up to 1h post-injury, the administration of JWH133 (1mg/kg, intraperitoneal injection) significantly attenuated brain edema at 24h post-GMH, which was reversed by a selective CB2R antagonist, SR144528 (3mg/kg, intraperitoneal injection). Long-term brain morphology and neurofunctional outcomes were also improved. In contrast, JWH133 did not have a noticeable effect on the hematoma volume during the acute phase. These data also showed that microglia activation and inflammatory cytokine (TNF-α) release were significantly inhibited by JWH133 after GMH. This current study suggests a potential clinical utility for CB2R agonists as a potential therapy to reduce neurological injury and improve patient outcomes after GMH.

  17. Aspirin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing the ERK/MAPK pathway.

    PubMed

    Gao, Hua; Cheng, Yuqing; Zong, Liguo; Huang, Linian; Qiao, Chenchen; Li, Wei; Gong, Beilei; Hu, Junfeng; Liu, Haitao; Wang, Xiaojing; Zhao, Chengling

    2017-01-01

    This study aimed to investigate the therapeutic effects of aspirin (ASA) and its potential mechanisms of action in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. PAH was induced in a rat model by a single intraperitoneal (IP) injection of MCT. Saline was injected in a control group. Two weeks following MCT injection, right ventricular systolic pressure (RVSP) and systolic blood pressure (SBP) were measured in six rats from each group to confirm establishment of a PAH model. The remaining MCT-treated rats were randomly allocated to receive IP injection of saline, ASA, or ERK1/2 inhibitor PD98059. Four weeks following treatment, RVSP was measured and all rats were sacrificed for histological study. There was no significant difference in SBP in any group two weeks following MCT administration. Nonetheless RVSP was significantly increased in the MCT group compared with the control group. At 6 weeks, ASA treatment remarkably attenuated MCT-induced increased RVSP, RV hypertrophy, and pulmonary artery remodeling compared with the MCT group. The density of pulmonary capillaries in ASA-treated rats was also dramatically increased. Treatment with ASA significantly inhibited the increased p-ERK1/2 and restored the impaired endothelial nitric oxide synthase (eNOS) in MCT-treated rats. This study demonstrated that ASA distinctively attenuates MCT-induced PAH by inhibition of the ERK1/2 signaling pathway.

  18. Imaging Rayleigh wave attenuation with USArray

    NASA Astrophysics Data System (ADS)

    Bao, Xueyang; Dalton, Colleen A.; Jin, Ge; Gaherty, James B.; Shen, Yang

    2016-07-01

    The EarthScope USArray provides an opportunity to obtain detailed images of the continental upper mantle at an unprecedented scale. The majority of mantle models derived from USArray data to date contain spatial variations in seismic-wave speed; however, in many cases these data sets do not by themselves allow a non-unique interpretation. Joint interpretation of seismic attenuation and velocity models can improve upon the interpretations based only on velocity and provide important constraints on the temperature, composition, melt content, and volatile content of the mantle. The surface wave amplitudes that constrain upper-mantle attenuation are sensitive to factors in addition to attenuation, including the earthquake source excitation, focusing and defocusing by elastic structure, and local site amplification. Because of the difficulty of isolating attenuation from these other factors, little is known about the attenuation structure of the North American upper mantle. In this study, Rayleigh wave traveltime and amplitude in the period range 25-100 s are measured using an interstation cross-correlation technique, which takes advantage of waveform similarity at nearby stations. Several estimates of Rayleigh wave attenuation and site amplification are generated at each period, using different approaches to separate the effects of attenuation and local site amplification on amplitude. It is assumed that focusing and defocusing effects can be described by the Laplacian of the traveltime field. All approaches identify the same large-scale patterns in attenuation, including areas where the attenuation values are likely contaminated by unmodelled focusing and defocusing effects. Regionally averaged attenuation maps are constructed after removal of the contaminated attenuation values, and the variations in intrinsic shear attenuation that are suggested by these Rayleigh wave attenuation maps are explored.

  19. Psoralea corylifolia L. Seed Extract Attenuates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice.

    PubMed

    Seo, Eunhui; Oh, Yoon Sin; Jun, Hee-Sook

    2016-02-06

    Nonalcoholic fatty liver disease (NAFLD), along with obesity, is increasing world-wide and is one of the major causes of chronic hepatic disease. The present study evaluated the ameliorative effect of extract of Psoralea corylifolia L. seed (PCS) on high fat diet-induced NAFLD in C57BL/6 mice after daily administration at 300 or 500 mg/kg for 12 weeks. Treatment with PCS extract significantly reduced body weight and blood glucose levels and improved glucose tolerance and insulin sensitivity. In addition, PCS extract treatment significantly attenuated lipid accumulation in liver and adipose tissue and reduced serum lipid and hepatic triglyceride levels. Furthermore, the expression of lipogenic genes and inflammatory genes were reduced, and the expression of fat oxidation-related genes was increased in the liver of PCS extract-treated mice compared with control mice. Our study suggests the therapeutic potential of PCS extract for NAFLD by inhibiting lipid accumulation and inflammation in liver.

  20. Psoralea corylifolia L. Seed Extract Attenuates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice

    PubMed Central

    Seo, Eunhui; Oh, Yoon Sin; Jun, Hee-Sook

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), along with obesity, is increasing world-wide and is one of the major causes of chronic hepatic disease. The present study evaluated the ameliorative effect of extract of Psoralea corylifolia L. seed (PCS) on high fat diet-induced NAFLD in C57BL/6 mice after daily administration at 300 or 500 mg/kg for 12 weeks. Treatment with PCS extract significantly reduced body weight and blood glucose levels and improved glucose tolerance and insulin sensitivity. In addition, PCS extract treatment significantly attenuated lipid accumulation in liver and adipose tissue and reduced serum lipid and hepatic triglyceride levels. Furthermore, the expression of lipogenic genes and inflammatory genes were reduced, and the expression of fat oxidation-related genes was increased in the liver of PCS extract-treated mice compared with control mice. Our study suggests the therapeutic potential of PCS extract for NAFLD by inhibiting lipid accumulation and inflammation in liver. PMID:26861390

  1. Attenuation of Scattered Thermal Energy Atomic Oxygen

    NASA Technical Reports Server (NTRS)

    Banks, Bruce a.; Seroka, Katelyn T.; McPhate, Jason B.; Miller, Sharon K.

    2011-01-01

    The attenuation of scattered thermal energy atomic oxygen is relevant to the potential damage that can occur within a spacecraft which sweeps through atomic oxygen in low Earth orbit (LEO). Although there can be significant oxidation and resulting degradation of polymers and some metals on the external surfaces of spacecraft, there are often openings on a spacecraft such as telescope apertures, vents, and microwave cavities that can allow atomic oxygen to enter and scatter internally to the spacecraft. Atomic oxygen that enters a spacecraft can thermally accommodate and scatter to ultimately react or recombine on surfaces. The atomic oxygen that does enter a spacecraft can be scavenged by use of high erosion yield polymers to reduce its reaction on critical surfaces and materials. Polyoxymethylene and polyethylene can be used as effective atomic oxygen scavenging polymers.

  2. Omega-3 polyunsaturated fatty acid and ursodeoxycholic acid have an additive effect in attenuating diet-induced nonalcoholic steatohepatitis in mice.

    PubMed

    Kim, Ja Kyung; Lee, Kwan Sik; Lee, Dong Ki; Lee, Su Yeon; Chang, Hye Young; Choi, Junjeong; Lee, Jung Il

    2014-12-19

    Nonalcoholic steatohepatitis (NASH) can progress into liver cirrhosis; however, no definite treatment is available. Omega-3 polyunsaturated fatty acid (omega-3) has been reported to alleviate experimental NASH, although its beneficial effect was not evident when tested clinically. Thus, this study aimed to investigate the additive effect of omega-3 and ursodeoxycholic acid (UDCA) on diet-induced NASH in mice. C57BL/6 mice were given a high-fat diet (HFD) for 24 weeks, at which point the mice were divided into three groups and fed HFD alone, HFD with omega-3 or HFD with omega-3 in combination with UDCA for another 24 weeks. Feeding mice an HFD and administering omega-3 improved histologically assessed liver fibrosis, and UDCA in combination with omega-3 further attenuated this disease. The assessment of collagen α1(I) expression agreed with the histological evaluation. Omega-3 in combination with UDCA resulted in a significant attenuation of inflammation whereas administering omega-3 alone failed to improve histologically assessed liver inflammation. Quantitative analysis of tumor necrosis factor α showed an additive effect of omega-3 and UDCA on liver inflammation. HFD-induced hepatic triglyceride accumulation was attenuated by omega-3 and adding UDCA accentuated this effect. In accordance with this result, the expression of sterol regulatory binding protein-1c decreased after omega-3 administration and adding UDCA further diminished SREBP-1c expression. The expression of inducible nitric oxide synthase (iNOS), which may reflect oxidative stress-induced tissue damage, was suppressed by omega-3 administration and adding UDCA further attenuated iNOS expression. These results demonstrated an additive effect of omega-3 and UDCA for alleviating fibrosis, inflammation and steatosis in diet-induced NASH.

  3. Oral administration of corn zein hydrolysate stimulates GLP-1 and GIP secretion and improves glucose tolerance in male normal rats and Goto-Kakizaki rats.

    PubMed

    Higuchi, Noriyuki; Hira, Tohru; Yamada, Nao; Hara, Hiroshi

    2013-09-01

    We have previously demonstrated that ileal administration of the dietary protein hydrolysate prepared from corn zein (ZeinH) stimulated glucagon-like peptide-1 (GLP-1) secretion and attenuated hyperglycemia in rats. In this study, to examine whether oral administration of ZeinH improves glucose tolerance by stimulating GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion, glucose tolerance tests were performed in normal Sprague-Dawley male rats and diabetic Goto-Kakizaki (GK) male rats. The test solution was gavaged before ip glucose injection in normal rats or gavaged together with glucose in GK rats. Blood samples were collected from the tail vein or by using the jugular catheter to measure glucose, insulin, GLP-1, and GIP levels. In the ip glucose tolerance test, oral administration of ZeinH (2 g/kg) significantly suppressed the glycemic response accompanied by an immediate increase in plasma GLP-1 and GIP levels in normal rats. In contrast, oral administration of another dietary peptide, meat hydrolysate, did not elicit a similar effect. The glucose-lowering effect of ZeinH was attenuated by a GLP-1 receptor antagonist or by a GIP receptor antagonist. Furthermore, oral ZeinH induced GLP-1 secretion and reduced glycemic response in GK rats under the oral glucose tolerance test. These results indicate that the oral administration of the dietary peptide ZeinH improves glucose tolerance in normal and diabetic rats by its incretin-releasing activity, namely, the incretinotropic effect.

  4. Experimental study of seismic attenuation in partially saturated porous media

    NASA Astrophysics Data System (ADS)

    Barrière, Julien; Bordes, Clarisse; Sénéchal, Pascale

    2010-05-01

    Nowadays, it is well admitted that hydrogeological properties of the porous media (porosity, fluid saturation and permeability) can influence seismic properties. In geophysics, the major theory which links hydrogeological and seismic parameters is poroelasticity proposed by Biot (1956). The Biot relaxation process is due to the relative displacement of fluid in comparison to the solid which causes a significant attenuation of seismic waves, notably in unconsolidated medium. In partially saturated medium, pore fluids are considered as a perfect mixture and so called 'effective fluid'. However, in more consolidated rocks, the Biot theory is not sufficient to explain the attenuation level as measured from field seismic and sonic log data. In the last decade, some authors provide new theories to understand the attenuation caused by the interaction of the different fluids. Most experiments are done in the ultrasonic frequency range, where sources of attenuation (like scattering or local fluid flow) are different as in the low frequency range where the wavelength is greater than heterogeneities size. In this way, we propose a forward-looking experiment with the use of a vertical impulsionnal seismic source which have a strong amplitude spectrum ranging from 100Hz to 8kHz. We study three different unconsolidated porous media at atmospheric pressure: fine-grained sand, coarsed-grained sand and coarse gravel. Water content is measured with a calibrated capacitance probe and temperature effects are corrected. Seismic wave propagation is recorded by piezoelectric accelerometers designed for frequencies below 10kHz. The water injection is done by imbibition. We propose to analyse the attenuation in the [100Hz-1.5kHz] frequency range for the studied media with various water saturation levels. The attenuation varies according to the porous medium and the water content and appears more significant at dry condition and at high saturation level. The weak cohesion at dry condition

  5. Space Shuttle Crawler Transporter Sound Attenuation Study

    NASA Technical Reports Server (NTRS)

    Margasahayam, Ravi N.; MacDonald, Rod; Faszer, Clifford

    2004-01-01

    The crawler transporter (CT) is the world's largest tracked vehicle known, weighing 6 million pounds with a length of 131 feet and a width of 113 feet. The Kennedy Space Center (KSC) has two CTs that were designed and built for the Apollo program in the 1960's, maintained and retrofitted for use in the Space Shuttle program. As a key element of the Space Shuttle ground systems, the crawler transports the entire 12-million-pound stack comprising the orbiter, the mobile launch platform (MLP), the external tank (ET), and the solid rocket boosters (SRB) from the Vehicle Assembly Building (VAB) to the launch pad. This rollout, constituting a 3.5-5.0-mile journey at a top speed of 0.9 miles-per-hour, requires over 8 hours to reach either Launch Complex 39A or B. This activity is only a prelude to the spectacle of sound and fury of the Space Shuttle launch to orbit in less than 10 minutes and traveling at orbital velocities of Mach 24. This paper summarizes preliminary results from the Crawler Transporter Sound Attenuation Study, encompassing test and engineering analysis of significant sound sources to measure and record full frequency spectrum and intensity of the various noise sources and to analyze the conditions of vibration. Additionally, data such as ventilation criteria, plus operational procedures were considered to provide a comprehensive noise suppression design for implementation. To date, sound attenuation study and results on Crawler 2 have shown significant noise reductions ranging from 5 to 24 dBA.

  6. SEISMIC ATTENUATION FOR RESERVOIR CHARACTERIZATION

    SciTech Connect

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

    2003-12-01

    We have developed and tested technology for a new type of direct hydrocarbon detection. The method uses inelastic rock properties to greatly enhance the sensitivity of surface seismic methods to the presence of oil and gas saturation. These methods include use of energy absorption, dispersion, and attenuation (Q) along with traditional seismic attributes like velocity, impedance, and AVO. Our approach is to combine three elements: (1) a synthesis of the latest rock physics understanding of how rock inelasticity is related to rock type, pore fluid types, and pore microstructure, (2) synthetic seismic modeling that will help identify the relative contributions of scattering and intrinsic inelasticity to apparent Q attributes, and (3) robust algorithms that extract relative wave attenuation attributes from seismic data. This project provides: (1) Additional petrophysical insight from acquired data; (2) Increased understanding of rock and fluid properties; (3) New techniques to measure reservoir properties that are not currently available; and (4) Provide tools to more accurately describe the reservoir and predict oil location and volumes. These methodologies will improve the industry's ability to predict and quantify oil and gas saturation distribution, and to apply this information through geologic models to enhance reservoir simulation. We have applied for two separate patents relating to work that was completed as part of this project.

  7. Musa sapientum with exercises attenuates hyperglycemia and pancreatic islet cells degeneration in alloxan-diabetic rats

    PubMed Central

    Akinlolu, Adelaja Abdulazeez; Salau, Bamidele A.; Ekor, Martins; Otulana, Jubril

    2015-01-01

    Aim: We tested the hypothesis that administrations of methanolic extracts of Musa sapientum sucker (MEMS) with exercises attenuated hyperglycemia in alloxan-diabetic rats. Materials and Methods: A total of 40 adult male rats were divided into equal eight groups. Normoglycemic Group A was Control. Alloxan (180 mg/kg, i.p.) was administered to rats in Groups B - H to induce diabetes. Group B (diabetic control) received physiological saline. Groups C - H received MEMS (5 mg/kg), MEMS (10 mg/kg), Glibenclamide (5 mg/kg), MEMS (5 mg/kg) + exercises, MEMS (10 mg/kg) + exercises and Exercises only, respectively. Changes in body weight, blood glucose levels (BGL) and pancreatic histology were evaluated during or at the end of experiment. Body weights and BGL of rats were expressed as mean ± standard deviation and analyzed using the statistical software program SPSS 15. Statistical comparisons were done using the Student’s t-test for unpaired samples. Differences between groups were determined as significant at P ≤ 0.05. Results: Significantly (P < 0.05) decreased bodyweight was observed in B and H compared to A and C - G. Treatment with MEMS significantly (P < 0.05) decreased elevated BGL in C and D. Hypoglycemic effect of MEMS appeared enhanced with exercises in F and G. Exercises regimen alone (H) resulted in percentage reduction in BGL lower than those of C - G. Histopathological examinations revealed normal pancreas (A), atrophied islet cells (B), hyperplasia with adequate population of islet cells (C - G), and reduced hyperplasia of islet cells (H). Conclusion: MEMS with exercises attenuated hyperglycemia in alloxan-diabetic rats. PMID:26401408

  8. Transportation Security Administration

    MedlinePlus

    ... content Official website of the Department of Homeland Security Transportation Security Administration A - Z Index What Can I Bring? ... form Search the Site Main menu Administrator Travel Security Screening Special Procedures TSA Pre✓® Passenger Support Travel ...

  9. Administration on Aging

    MedlinePlus

    ... Federal Initiatives Career Opportunities Contact Us Administration on Aging (AoA) The Administration on Aging (AOA) is the ... themselves. Back to top Older Americans Act and Aging Network To meet the diverse needs of the ...

  10. Rehabilitation Services Administration

    MedlinePlus

    ... Contacts OSEP Reports & Resources RSA Welcome to RSA Rehabilitation Services Administration RSA Spotlight News Commissioner's Quarterly Newsletter ... The Office of Special Education and Rehabilitative Services’ Rehabilitation Services Administration is proud to announce the publication ...

  11. Administration on Aging

    MedlinePlus

    ... Administration on Aging Administration on Disabilities Center for Integrated Programs Center for Performance and Evaluation National Institute ... Project Aging Statistics Profile of Older Americans AGing Integrated Database (AGID) Census Data & Population Estimates Projected Future ...

  12. Orally administered live attenuated Salmonella Typhimurium protects mice against lethal infection with H1N1 influenza virus.

    PubMed

    Kamble, Nitin Machindra; Hajam, Irshad Ahmed; Lee, John Hwa

    2017-03-01

    Pre-stimulation of toll-like receptors (TLRs) by agonists has been shown to increase protection against influenza virus infection. In this study, we evaluated the protective response generated against influenza A/Puerto Rico/8/1934 (PR8; H1N1) virus by oral and nasal administration of live attenuated Salmonella enterica serovar Typhimurium, JOL911 strain, in mice. Oral and nasal inoculation of JOL911 significantly increased the mRNA copy number of TLR-2, TLR4 and TLR5, and downstream type I interferon (IFN) molecules, IFN-α and IFN-β, both in peripheral blood mononuclear cells (PBMCs) and in lung tissue. Similarly, the mRNA copy number of interferon-inducible genes (ISGs), Mx and ISG15, were significantly increased in both the orally and the nasally inoculated mice. Post PR8 virus lethal challenge, the nasal JOL911 and the PBS control group mice showed significant loss of body weight with 70% and 100% mortality, respectively, compared to only 30% mortality in the oral JOL911 group mice. Post sub-lethal challenge, the significant reduction in PR8 virus copy number in lung tissue was observed in oral [on day 4 and 6 post-challenge (dpc)] and nasal (on 4dpc) than the PBS control group mice. The lethal and sub-lethal challenge showed that the generated stimulated innate resistance (StIR) in JOL911 inoculated mice conferred resistance to acute and initial influenza infection but might not be sufficient to prevent the PR8 virus invasion and replication in the lung. Overall, the present study indicates that oral administration of attenuated S. Typhimurium can pre-stimulate multiple TLR pathways in mice to provide immediate early StIR against a lethal H1N1 virus challenge.

  13. Caffeine Attenuates Decreases in Leg Power Without Increased Muscle Damage.

    PubMed

    Ribeiro, Beatriz G; Morales, Anderson P; Sampaio-Jorge, Felipe; Barth, Thiago; de Oliveira, Marcio B C; Coelho, Gabriela M D O; Leite, Tiago C

    2016-08-01

    Ribeiro, BG, Morales, AP, Sampaio-Jorge, F, Barth, T, de Oliveira, MBC, Coelho, GMdO, and Leite, TC. Caffeine attenuates decreases in leg power without increased muscle damage. J Strength Cond Res 30(8): 2354-2360, 2016-Caffeine ingestion has been shown to be an effective ergogenic aid in several sports. Caffeine administration may increase exercise capacity, which could lead to a greater degree of muscle damage after exercise. This was a randomized, double-blind, placebo-controlled crossover study. Six male handball athletes ingested placebo (PLA) or caffeine (CAF) (6 mg·kg body mass) capsules on 2 different occasions. Sixty minutes after ingestion of the capsules, serum CAF levels were evaluated. Thereafter, all participants performed a protocol of vertical jumps (VJs). The protocol consisted of 4 sets of 30 seconds of continuous VJs with 60 seconds of recovery between sets. Blood lactate (LAC) and creatine kinase (CK) levels were determined before and after the protocol. We found significant differences in serum CAF levels between PLA (0.09 ± 0.18 µg·ml) vs. CAF (6.59 ± 4.44 µg·ml) (p < 0.001). Caffeine elicited a 5.23% (p ≤ 0.05) improvement in the leg power compared with PLA. The CAF trial displayed higher LAC (p ≤ 0.05) compared with PLA (6.26 ± 2.01 vs. 4.39 ± 2.42 mmol·L, respectively) after protocol of VJs, whereas no difference in CK was observed between trials (p > 0.05). These results indicate that immediate ingestion of CAF (6 mg·kg body weight) can reduce the level of muscle fatigue and preserve leg power during the test, possibly resulting in increase in LAC. There was no increase in muscle damage, which indicates that immediate administration of (6 mg·kg body weight) CAF is safe. Thus, nutritional interventions with CAF could help athletes withstand a greater physiological overload during high-intensity training sessions. The results of this study would be applicable to sports and activities that require repetitive leg power.

  14. MTBE, TBA, and TAME attenuation in diverse hyporheic zones

    USGS Publications Warehouse

    Landmeyer, J.E.; Bradley, P.M.; Trego, D.A.; Hale, K.G.; Haas, J.E.

    2010-01-01

    Groundwater contamination by fuel-related compounds such as the fuel oxygenates methyl tert-butyl ether (MTBE), tert-butyl alcohol (TBA), and tert-amyl methyl ether (TAME) presents a significant issue to managers and consumers of groundwater and surface water that receives groundwater discharge. Four sites were investigated on Long Island, New York, characterized by groundwater contaminated with gasoline and fuel oxygenates that ultimately discharge to fresh, brackish, or saline surface water. For each site, contaminated groundwater discharge zones were delineated using pore water geochemistry data from 15 feet (4.5 m) beneath the bottom of the surface water body in the hyporheic zone and seepage-meter tests were conducted to measure discharge rates. These data when combined indicate that MTBE, TBA, and TAME concentrations in groundwater discharge in a 5-foot (1.5-m) thick section of the hyporheic zone were attenuated between 34% and 95%, in contrast to immeasurable attenuation in the shallow aquifer during contaminant transport between 0.1 and 1.5 miles (0.1 to 2.4 km). The attenuation observed in the hyporheic zone occurred primarily by physical processes such as mixing of groundwater and surface water. Biodegradation also occurred as confirmed in laboratory microcosms by the mineralization of U- 14C-MTBE and U- 14C-TBA to 14CO2 and the novel biodegradation of U- 14C-TAME to 14CO2 under oxic and anoxic conditions. The implication of fuel oxygenate attenuation observed in diverse hyporheic zones suggests an assessment of the hyporheic zone attenuation potential (HZAP) merits inclusion as part of site assessment strategies associated with monitored or engineered attenuation. ?? 2009 National Ground Water Association.

  15. Legal and Administrative Language

    ERIC Educational Resources Information Center

    Schwarz, Hans

    1977-01-01

    A discussion of legal and administrative language, and the necessity for accurate translation of this language in the field of international relations. Topics treated are: characteristic features of legal and administrative terminology; the interpretation of it; and the technique of translating legal and administrative texts. (AMH)

  16. Women in Administration 1978.

    ERIC Educational Resources Information Center

    National Association of State Universities and Land Grant Colleges, Washington, DC. Office of Communications Services.

    In a survey by the National Association of State Universities and Land-Grant Colleges (NASULGC), women are shown to hold 2,905 of the 13,638 administrative positions reported by 106 major U.S. public universities--slightly more than 21 percent of the administrators at state and land-grant universities. The median number of women administrators at…

  17. School Business Administration.

    ERIC Educational Resources Information Center

    Jordan, K. Forbis; And Others

    This textbook reviews the principal concerns within each of 13 major responsibility areas in school business administration. The first chapter assesses the political, social, and economic context in which schools function and school administrators work. The role and function of the school business administrator within this context is addressed in…

  18. Calculation Of Pneumatic Attenuation In Pressure Sensors

    NASA Technical Reports Server (NTRS)

    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.

  19. Global Attenuation Model of the Upper Mantle

    NASA Astrophysics Data System (ADS)

    Adenis, A.; Debayle, E.; Ricard, Y. R.

    2015-12-01

    We present a three-dimensional shear attenuation model based on a massive surface wave data-set (372,629 Rayleigh waveforms analysed in the period range 50-300s by Debayle and Ricard, 2012). For each seismogram, this approach yields depth-dependent path average models of shear velocity and quality factor, and a set of fundamental and higher-mode dispersion and attenuation curves. We combine these attenuation measurements in a tomographic inversion after a careful rejection of the noisy data. We first remove data likely to be biased by a poor knowledge of the source. Then we assume that waves corresponding to events having close epicenters and recorded at the same station sample the same elastic and anelastic structure, we cluster the corresponding rays and average the attenuation measurements. Logarithms of the attenuations are regionalized using the non-linear east square formalism of Tarantola and Valette (1982), resulting in attenuation tomographic maps between 50s and 300s. After a first inversion, outlyers are rejected and a second inversion yields a moderate variance reduction of about 20%. We correct the attenuation curves for focusing effect using the linearized ray theory of Woodhouse and Wong (1986). Accounting for focussing effects allows building tomographic maps with variance reductions reaching 40%. In the period range 120-200s, the root mean square of the model perturbations increases from about 5% to 20%. Our 3-D attenuation models present strong agreement with surface tectonics at period lower than 200s. Areas of low attenuation are located under continents and areas of high attenuation are associated with oceans. Surprisingly, although mid oceanic ridges are located in attenuating regions, their signature, even if enhanced by focusing corrections, remains weaker than in the shear velocity models. Synthetic tests suggests that regularisation contributes to damp the attenuation signature of ridges, which could therefore be underestimated.

  20. General relationships between ultrasonic attenuation and dispersion

    NASA Technical Reports Server (NTRS)

    Odonnell, M.; Jaynes, E. T.; Miller, J. G.

    1978-01-01

    General relationships between the ultrasonic attenuation and dispersion are presented. The validity of these nonlocal relationships hinges only on the properties of causality and linearity, and does not depend upon details of the mechanism responsible for the attenuation and dispersion. Approximate, nearly local relationships are presented and are demonstrated to predict accurately the ultrasonic dispersion in solutions of hemoglobin from the results of attenuation measurements.

  1. Optimal ultrasonic array focusing in attenuative media.

    PubMed

    Ganguli, A; Gao, R X; Liang, K; Jundt, J

    2011-12-01

    This paper presents a parametric study on the efficiency of ultrasound focusing in an attenuative medium, using phased arrays. Specifically, an analytical model of ultrasound wave focusing in a homogeneous, isotropic and attenuative fluid with point sources is presented. Calculations based on the model have shown that in an attenuative medium, an optimum frequency exists for the best focusing performance for a particular size of aperture and focal distance. The effect of different f numbers on the focusing performance in the attenuative medium is further investigated. The information obtained from the analytical model provides insights into the design and installation of a phased transducer array for energy efficient wave focusing.

  2. Differential dust attenuation in CALIFA galaxies

    NASA Astrophysics Data System (ADS)

    Vale Asari, N.; Cid Fernandes, R.; Amorim, A. L.; Lacerda, E. A. D.; Schlickmann, M.; Wild, V.; Kennicutt, R. C.

    2016-06-01

    Dust attenuation has long been treated as a simple parameter in SED fitting. Real galaxies are, however, much more complicated: The measured dust attenuation is not a simple function of the dust optical depth, but depends strongly on galaxy inclination and the relative distribution of stars and dust. We study the nebular and stellar dust attenuation in CALIFA galaxies, and propose some empirical recipes to make the dust treatment more realistic in spectral synthesis codes. By adding optical recombination emission lines, we find better constraints for differential attenuation. Those recipes can be applied to unresolved galaxy spectra, and lead to better recovered star formation rates.

  3. Attenuation of gentamycin-induced nephrotoxicity in rats by dietary inclusion of ginger (Zingiber officinale) and turmeric (Curcuma longa) rhizomes.

    PubMed

    Ademiluyi, Adedayo O; Oboh, Ganiyu; Ogunsuyi, Opeyemi B; Akinyemi, Ayodele J

    2012-10-01

    This study sought to investigate the modulatory effects of dietary inclusion of ginger (Zingiber officinale) and turmeric (Curcuma longa) rhizomes on antioxidant status and renal damage induced by gentamycin in rats. Renal damage was induced in albino rats pretreated with dietary inclusion of ginger and turmeric (2% and 4%) by intraperitoneal (i.p.) administration of gentamycin (100 mg/kg body weight) for three days. Assays for renal damage biomarkers (plasma creatinine, plasma urea, blood urea nitrogen and plasma uric acid), malondialdehyde (MDA) content and reduced glutathione (GSH) content as well as renal antioxidant enzymes (catalase, glutathione-S-transferase (GST), glutathione peroxidase (GPx) and superoxide dismutase (SOD)) were carried out. The study revealed significant (p < 0.05) increases in renal damage biomarkers following gentamycin administration with severe alteration in kidney antioxidant status. However, pretreatment with ginger and turmeric rhizome (2% and 4%) prior to gentamycin administration significantly (p < 0.05) protected the kidney and attenuated oxidative stress by modulating renal damage and antioxidant indices. This finding therefore suggests that dietary inclusion of ginger and turmeric rhizomes may protect against gentamycin-induced nephrotoxicity and oxidative stress.

  4. Acetaminophen Attenuates Lipid Peroxidation in Children Undergoing Cardiopulmonary Bypass

    PubMed Central

    Simpson, Scott A.; Zaccagni, Hayden; Bichell, David P.; Christian, Karla G.; Mettler, Bret A.; Donahue, Brian S.; Roberts, L. Jackson; Pretorius, Mias

    2014-01-01

    Objective Hemolysis, occurring during cardiopulmonary bypass (CPB), is associated with lipid peroxidation and postoperative acute kidney injury (AKI). Acetaminophen (ApAP) inhibits lipid peroxidation catalyzed by hemeproteins and in an animal model attenuated rhabdomyolysis-induced AKI. This pilot study tests the hypothesis that ApAP attenuates lipid peroxidation in children undergoing CPB. Design Single center prospective randomized double blinded study. Setting University-affiliated pediatric hospital. Patients Thirty children undergoing elective surgical correction of a congenital heart defect. Interventions Patients were randomized to ApAP (OFIRMEV® (acetaminophen) injection, Cadence Pharmaceuticals, San Diego, CA) or placebo every 6 hours for 4 doses starting before the onset of CPB. Measurement and Main Results Markers of hemolysis, lipid peroxidation (isofurans and F2-isoprostanes) and AKI were measured throughout the perioperative period. CPB was associated with a significant increase in free hemoglobin (from a pre-bypass level of 9.8±6.2 mg/dl to a peak of 201.5±42.6 mg/dl post-bypass). Plasma and urine isofuran and F2-isoprostane concentrations increased significantly during surgery. The magnitude of increase in plasma isofurans was greater than the magnitude in increase in plasma F2-isoprostanes. ApAP attenuated the increase in plasma isofurans compared to placebo (P=0.02 for effect of study drug). There was no significant effect of ApAP on plasma F2-isoprostanes or urinary makers of lipid peroxidation. ApAP did not affect postoperative creatinine, urinary neutrophil gelatinase-associated lipocalin or prevalence of AKI. Conclusion CPB in children is associated with hemolysis and lipid peroxidation. ApAP attenuated the increase in plasma isofuran concentrations. Future studies are needed to establish whether other therapies that attenuate or prevent the effects of free hemoglobin result in more effective inhibition of lipid peroxidation in patients

  5. Effects of Proton Pump Inhibitor Administration and Intake of a Combination of Yogurt and Galactooligosaccharides on Bone and Mineral Metabolism in Rats

    PubMed Central

    Takasugi, Satoshi; Shioyama, Miho; Kitade, Masami; Nagata, Masashi; Yamaji, Taketo

    2016-01-01

    The aim of this study was to investigate the effects of proton pump inhibitor (PPI), the most potent acid-suppressing drug, administration and intake of a combination of yogurt and galactooligosaccharides (YG) on bone and mineral metabolism in adult rats. Twelve-week-old male Wistar rats were divided into three groups: a control group fed the control diet with vehicle administration, a PPI group fed the control diet with PPI administration and a YG + PPI group fed the YG diet with PPI administration. All of the groups received their respective experimental diets and daily subcutaneous injection of the vehicle or PPI for 12 weeks. The PPI group showed significantly lower bone mineral density (BMD) of the femur and the lumbar vertebrae and serum fibroblast growth factor 23 (FGF23) and significantly higher phosphorus absorption and serum 1,25-dihydroxyvitamin D (1,25(OH)2D) than the control group, although PPI did not affect calcium absorption. The PPI + YG group showed significantly higher BMD and serum FGF23 and significantly lower phosphorus absorption and serum 1,25(OH)2D than the PPI group. Furthermore, the PPI + YG group showed higher calcium absorption than the control group. These results suggest that although PPI administration did not affect calcium absorption, it adversely affected BMD and influenced phosphorus metabolism in adult rats. Furthermore, the YG diet beneficially affected BMD and attenuated the effects of PPI administration on phosphorus metabolism. PMID:27775655

  6. Ghrelin Attenuates Intestinal Barrier Dysfunction Following Intracerebral Hemorrhage in Mice

    PubMed Central

    Cheng, Yijun; Wei, Yongxu; Yang, Wenlei; Cai, Yu; Chen, Bin; Yang, Guoyuan; Shang, Hanbing; Zhao, Weiguo

    2016-01-01

    Intestinal barrier dysfunction remains a critical problem in patients with intracerebral hemorrhage (ICH) and is associated with poor prognosis. Ghrelin, a brain-gut peptide, has been shown to exert protection in animal models of gastrointestinal injury. However, the effect of ghrelin on intestinal barrier dysfunction post-ICH and its possible underlying mechanisms are still unknown. This study was designed to investigate whether ghrelin administration attenuates intestinal barrier dysfunction in experimental ICH using an intrastriatal autologous blood infusion mouse model. Our data showed that treatment with ghrelin markedly attenuated intestinal mucosal injury at both histomorphometric and ultrastructural levels post-ICH. Ghrelin reduced ICH-induced intestinal permeability according to fluorescein isothiocyanate conjugated-dextran (FITC-D) and Evans blue extravasation assays. Concomitantly, the intestinal tight junction-related protein markers, Zonula occludens-1 (ZO-1) and claudin-5 were upregulated by ghrelin post-ICH. Additionally, ghrelin reduced intestinal intercellular adhesion molecule-1 (ICAM-1) expression at the mRNA and protein levels following ICH. Furthermore, ghrelin suppressed the translocation of intestinal endotoxin post-ICH. These changes were accompanied by improved survival rates and an attenuation of body weight loss post-ICH. In conclusion, our results suggest that ghrelin reduced intestinal barrier dysfunction, thereby reducing mortality and weight loss, indicating that ghrelin is a potential therapeutic agent in ICH-induced intestinal barrier dysfunction therapy. PMID:27929421

  7. Aripiprazole attenuates established behavioral sensitization induced by methamphetamine.

    PubMed

    Futamura, Takashi; Akiyama, Satoshi; Sugino, Haruhiko; Forbes, Andy; McQuade, Robert D; Kikuchi, Tetsuro

    2010-08-16

    Psychostimulant-induced behavioral sensitization is an experimental model of the stimulant psychosis and the vulnerability to relapse in schizophrenia. This study investigated the effects of aripiprazole, an antipsychotic drug that has dopamine D2 receptor partial agonist activity, on established sensitization induced by methamphetamine (MAP) in mice. Repeated treatment with MAP (1.0mg/kg, s.c.) for 10 days progressively increased the ability of MAP to increase locomotor activity. The enhanced locomotion induced by a challenge dose of MAP (0.24 mg/kg, s.c.) also occurred after withdrawal from MAP pretreatment. Repeated treatment with aripiprazole from days 10 to 14 during withdrawal from MAP administration attenuated the effect of MAP pretreatment, enhancing the motor response to a challenge dose of stimulant 3 days after the aripiprazole preparation. In contrast, sulpiride, a dopamine D2 receptor specific antagonist, and risperidone, a serotonin 5-HT2 and dopamine D2 receptor antagonist, did not show effects similar to aripiprazole. The attenuation effect of aripiprazole was blocked by pretreatment with the specific serotonin 5-HT1A antagonist WAY100635. These results of aripiprazole suggest that the attenuation effect of aripiprazole was mediated by 5-HT1A receptors and imply that aripiprazole may have therapeutic value in treating drug-induced psychosis and schizophrenia.

  8. Resveratrol Attenuates Both Small Bowel and Liver Changes in Obstructive Jaundice

    PubMed Central

    Temi, Volkan; Okay, Erdem; Güneş, Abdullah; Şimşek, Turgay; Çekmen, Mustafa; Bilgili, Ümit; Gürbüz, Yeşim

    2014-01-01

    Background: It is well known that mucosal changes and alterations in liver function occur in the experimental obstructive jaundice model. Aims: We aimed to evaluate the effect of resveratrol on obstructive jaundice-induced changes in the small bowel mucosa and liver using ischaemia-modified albumin as a marker of oxidative damage. Study Design: Animal experimentation. Methods: The study used a rodent experimental model of obstructive jaundice, including a sham group (1), a control group (2), and a study group (3). Wistar albino rats were used. Jaundice was produced by ligation of the bile duct in Groups 2 and 3. In Group 3, resveratrol was administered intraperitoneally for 14 days. Results: In terms of the structure and the size of the mucosal villi, significant thickening and blunting were detected in Group 2 compared with Group 1. These changes were significantly less noticeable in Group 3 compared with Group 2. Levels of ischaemia-modified albumin were significantly higher in Group 2 compared with those in Group 1, and they were significantly decreased in Group 3 compared with Group 2. Conclusion: Resveratrol administration to obstructive jaundiced rats reduced the organic effects of obstructive jaundice on small bowel mucosa and liver oxidative stress. We believe that this reduction might attenuate bacterial translocation and systemic effects of secreted cytokines. PMID:25207176

  9. Homocysteine-induced attenuation of vascular endothelium-dependent hyperalgesia in the rat

    PubMed Central

    Joseph, Elizabeth K.; Green, Paul G.; Ferrari, Luiz F.; Levine, Jon D.

    2014-01-01

    We have recently demonstrated a role of the vascular endothelium in peripheral pain mechanism by disrupting endothelial cell function using intravascular administration of octoxynol-9, a non-selective membrane active agent. As an independent test of the role of endothelial cells in pain mechanisms, we evaluated the effect of homocysteine, an agent that damages endothelial cell function. Mechanical stimulus-induced enhancement of endothelin-1 hyperalgesia in the gastrocnemius muscle of the rat was first prevented then enhanced by intravenous administration of homocysteine, but was only inhibited by its precursor, methionine. Both homocysteine and methionine significantly attenuated mechanical hyperalgesia in two models of ergonomic muscle pain, induced by exposure to vibration, and by eccentric exercise, and cutaneous mechanical hyperalgesia in an ischemia-reperfusion injury model of Complex Regional Pain Syndrome type I, all previously shown responsive to octoxynol-9. This study provides independent support for a role of the endothelial cell in pain syndromes thought to have a vascular basis, and suggests that substances that are endothelial cell toxins can enhance vascular pain. PMID:25451284

  10. Attenuation of allergic airway inflammation and hyperresponsiveness in a murine model of asthma by silver nanoparticles

    PubMed Central

    Park, Hee Sun; Kim, Keun Hwa; Jang, Sunhyae; Park, Ji Won; Cha, Hye Rim; Lee, Jeong Eun; Kim, Ju Ock; Kim, Sun Young; Lee, Choong Sik; Kim, Joo Pyung; Jung, Sung Soo

    2010-01-01

    The use of silver in the past demonstrated the certain antimicrobial activity, though this has been replaced by other treatments. However, nanotechnology has provided a way of producing pure silver nanoparticles, and it shows cytoprotective activities and possible pro-healing properties. But, the mechanism of silver nanoparticles remains unknown. This study was aimed to investigate the effects of silver nanoparticles on bronchial inflammation and hyperresponsiveness. We used ovalbumin (OVA)-inhaled female C57BL/6 mice to evaluate the roles of silver nanoparticles and the related molecular mechanisms in allergic airway disease. In this study with an OVA-induced murine model of allergic airway disease, we found that the increased inflammatory cells, airway hyperresponsiveness, increased levels of IL-4, IL-5, and IL-13, and the increased NF-κB levels in lungs after OVA inhalation were significantly reduced by the administration of silver nanoparticles. In addition, we have also found that the increased intracellular reactive oxygen species (ROS) levels in bronchoalveolar lavage fluid after OVA inhalation were decreased by the administration of silver nanoparticles. These results indicate that silver nanoparticles may attenuate antigen-induced airway inflammation and hyperresponsiveness. And antioxidant effect of silver nanoparticles could be one of the molecular bases in the murine model of asthma. These findings may provide a potential molecular mechanism of silver nanoparticles in preventing or treating asthma. PMID:20957173

  11. Tyrosol attenuates ischemia-reperfusion-induced kidney injury via inhibition of inducible nitric oxide synthase.

    PubMed

    Wang, Pengqi; Zhu, Qingjun; Wu, Nan; Siow, Yaw L; Aukema, Harold; O, Karmin

    2013-04-17

    Tyrosol is a natural phenolic antioxidant compound. Oxidative stress represents one of the important mechanisms underlying ischemia-reperfusion-induced kidney injury. The aim of this study was to investigate the effect of tyrosol against ischemia-reperfusion-induced acute kidney injury. The left kidney of Sprague-Dawley rats was subjected to 45 min of ischemia followed by reperfusion for 6 h. Ischemia-reperfusion caused an increase in peroxynitrite formation and lipid peroxidation. The level of nitric oxide (NO) metabolites and the mRNA of inducible nitric oxide synthase (iNOS) were elevated in ischemia-reperfused kidneys. Administration of tyrosol (100 mg/kg body weight) to rats prior to the induction of ischemia significantly reduced peroxynitrite formation, lipid peroxidation, and the level of NO metabolites. Tyrosol administration also attenuated ischemia-reperfusion-induced NF-κB activation and iNOS expression. Such a treatment improved kidney function. Results suggest that tyrosol may have a protective effect against acute kidney injury through inhibition of iNOS-mediated oxidative stress.

  12. 6-Hydroxydopamine injections into the nigrostriatal pathway attenuate striatal malonate and 3-nitropropionic acid lesions.

    PubMed

    Maragos, W F; Jakel, R J; Pang, Z; Geddes, J W

    1998-12-01

    The mitochondrial inhibitors malonate and 3-nitropropionic (3NP) acid are potent neurotoxins in vivo. Administration of these compounds results in neuronal loss similar to that seen in Huntington's disease. Although the mechanism of cell death produced by these compounds likely involves activation of N-methyl-D-aspartate receptors, it remains unclear why the striatum demonstrates regional susceptibility to the toxicity of these and other mitochondrial poisons. We hypothesized that dopamine, a weak neurotoxin that occurs in high concentrations in the striatum, may contribute to the neuronal damage caused by mitochondrial inhibition. We investigated whether depletion of striatal dopamine using the catecholaminergic toxin 6-hydroxydopamine would attenuate lesions induced by mitochondrial inhibition. We found that dopamine depletion reduced significantly the extent of histological damage in the striatum elicited by both intraparenchymal injections of 0.8 micromol malonate and 20 mg/kg systemic administration of 3NP. These data suggest that dopamine or one of its metabolites may contribute to mitochondrial toxin-induced cell death.

  13. Puerarin, isolated from Pueraria lobata (Willd.), protects against diabetic nephropathy by attenuating oxidative stress.

    PubMed

    Xu, Xiaohui; Zheng, Ni; Chen, Zhaoni; Huang, Wansu; Liang, Tao; Kuang, Hai

    2016-10-15

    In this study, we evaluated the effect of puerarin (PR) on diabetic nephropathy (DN) in streptozotocin (STZ)-induced diabetic mice. The fasting blood glucose (FBG), blood urea nitrogen (BUN) and serum creatinine (Scr), as well as 24-hour urine protein levels were effectively ameliorated in DN mice treated with PR (20, 40, 80mg/kg/day). Furthermore, PR treatment markedly resulted in down-regulation of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS) in kidney. Interestingly, the activities of manganese superoxide dismutase (MnSOD) and catalase (CAT) were increased by PR. An improvement in kidney tissue damage could be observed after PR administration. Further ultrastructural investigation revealed a dramatically ameliorative effect of PR on mitochondrial damage. Meanwhile, the silent information regulator 1 (SIRT1), forkhead box protein O1 (FOXO1) and alpha subunit of peroxisome proliferators-activated receptor-gamma coactivator-1 (PGC-1α) expressions were significantly up-regulated at protein level by PR administration in renal cortex. However, the protein expression of nuclear-factor kappa B (NF-κB) was down-regulated in PR groups. Our present study demonstrates the hypoglycemic and renal protective effects of PR in DN mice, which support its anti-diabetic property. PR exerts its renal protection effect probably via the mechanism of attenuating SIRT1/FOXO1 pathway for renal protection.

  14. Aerosols attenuating the solar radiation collected by solar tower plants: The horizontal pathway at surface level

    NASA Astrophysics Data System (ADS)

    Elias, Thierry; Ramon, Didier; Dubus, Laurent; Bourdil, Charles; Cuevas-Agulló, Emilio; Zaidouni, Taoufik; Formenti, Paola

    2016-05-01

    Aerosols attenuate the solar radiation collected by solar tower plants (STP), along two pathways: 1) the atmospheric column pathway, between the top of the atmosphere and the heliostats, resulting in Direct Normal Irradiance (DNI) changes; 2) the grazing pathway close to surface level, between the heliostats and the optical receiver. The attenuation along the surface-level grazing pathway has been less studied than the aerosol impact on changes of DNI, while it becomes significant in STP of 100 MW or more. Indeed aerosols mostly lay within the surface atmospheric layer, called the boundary layer, and the attenuation increases with the distance covered by the solar radiation in the boundary layer. In STP of 100 MW or more, the distance between the heliostats and the optical receiver becomes large enough to produce a significant attenuation by aerosols. We used measured aerosol optical thickness and computed boundary layer height to estimate the attenuation of the solar radiation at surface level at Ouarzazate (Morocco). High variabilities in aerosol amount and in vertical layering generated a significant magnitude in the annual cycle and significant inter-annual changes. Indeed the annual mean of the attenuation caused by aerosols over a 1-km heliostat-receiver distance was 3.7% in 2013, and 5.4% in 2014 because of a longest desert dust season. The monthly minimum attenuation of less than 3% was observed in winter and the maximum of more than 7% was observed in summer.

  15. Estradiol attenuates spinal cord injury-induced pain by suppressing microglial activation in thalamic VPL nuclei of rats.

    PubMed

    Saghaei, Elham; Abbaszadeh, Fatemeh; Naseri, Kobra; Ghorbanpoor, Samar; Afhami, Mina; Haeri, Ali; Rahimi, Farzaneh; Jorjani, Masoumeh

    2013-04-01

    In our previous study we showed that central pain syndrome (CPS) induced by electrolytic injury caused in the unilateral spinothalamic tract (STT) is a concomitant of glial alteration at the site of injury. Here, we investigated the activity of glial cells in thalamic ventral posterolateral nuclei (VPL) and their contribution to CPS. We also examined whether post-injury administration of a pharmacological dose of estradiol can attenuate CPS and associated molecular changes. Based on the results,in the ipsilateral VPL the microglial phenotype switched o hyperactive mode and Iba1 expression was increased significantly on days 21 and 28 post-injury. The same feature was observed in contralateral VPL on day 28 (P<.05). These changes were strongly correlated with the onset of CPS (r(2)=0.670). STT injury did not induce significant astroglial response in both ipsilateral and contralateral VPL. Estradiol attenuated bilateral mechanical hypersensitivity 14 days after STT lesion (P<.05). Estradiol also suppressed microglial activation in the VPL. Taken together, these findings indicate that selective STT lesion induces bilateral microglia activation in VPL which might contribute to mechanical hypersensitivity. Furthermore, a pharmacological dose of estradiol reduces central pain possibly via suppression of glial activity in VPL region.

  16. Paeoniflorin attenuates neuroinflammation and dopaminergic neurodegeneration in the MPTP model of Parkinson's disease by activation of adenosine A1 receptor.

    PubMed

    Liu, Hua-Qing; Zhang, Wei-Yu; Luo, Xue-Ting; Ye, Yang; Zhu, Xing-Zu

    2006-06-01

    1. This study examined whether Paeoniflorin (PF), the major active components of Chinese herb Paeoniae alba Radix, has neuroprotective effect in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). 2. Subcutaneous administration of PF (2.5 and 5 mg kg(-1)) for 11 days could protect tyrosine hydroxylase (TH)-positive substantia nigra neurons and striatal nerve fibers from death and bradykinesia induced by four-dose injection of MPTP (20 mg kg(-1)) on day 8. 3. When given at 1 h after the last dose of MPTP, and then administered once a day for the following 3 days, PF (2.5 and 5 mg kg(-1)) also significantly attenuated the dopaminergic neurodegeneration in a dose-dependent manner. Post-treatment with PF (5 mg kg(-1)) significantly attenuated MPTP-induced proinflammatory gene upregulation and microglial and astrocytic activation. 4. Pretreatment with 0.3 mg kg(-1) 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A1 receptor (A1AR) antagonist, 15 min before each dose of PF, reversed the neuroprotective and antineuroinflammatory effects of PF. 5. In conclusion, this study demonstrated that PF could reduce the MPTP-induced toxicity by inhibition of neuroinflammation by activation of the A1AR, and suggested that PF might be a valuable neuroprotective agent for the treatment of PD.

  17. Inhibition of leukotriene B4 receptor 1 attenuates lipopolysaccharide-induced cardiac dysfunction: role of AMPK-regulated mitochondrial function

    PubMed Central

    Sun, Meng; Wang, Rui; Han, Qinghua

    2017-01-01

    Leukotriene B4 (LTB4)-mediated leukocyte recruitment and inflammatory cytokine production make crucial contributions to chronic inflammation and sepsis; however, the role of LTB4 in lipopolysaccharide (LPS)-induced cardiac dysfunction remains unclear. Therefore, the present study addressed this issue using an LTB4 receptor 1 (BLT1) inhibitor. Administration of LPS to mice resulted in decreased cardiovascular function. Inhibition of LTB4/BLT1 with the BLT1 inhibitor U75302 significantly improved survival and attenuated the LPS-induced acute cardiac dysfunction. During LPS challenge, the phosphorylated AMPK/ACC signaling pathway was slightly activated, and this effect was enhanced by U75302. Additionally, pNF-κB, Bax and cleaved caspase-3 were upregulated by LPS, and Bcl-2, IκB-α, mitochondrial complex I, complex II, and OPA1 were downregulated; however, these effects were reversed by U75302. The results indicated that the BLT1 antagonist suppressed cardiac apoptosis, inflammation, and mitochondrial impairment. Furthermore, the protection provided by the BLT1 inhibitor against LPS-induced cardiac dysfunction was significantly reversed by the AMPK inhibitor Compound C. In conclusion, inhibiting the LTB4/BLT1 signaling pathway via AMPK activation is a potential treatment strategy for septic cardiac dysfunction because it efficiently attenuates cardiac apoptosis, which may occur via the inhibition of inflammation and mitochondrial dysfunction. PMID:28290498

  18. Attenuation of experimental autoimmune neuritis with locally administered lovastatin-encapsulating poly(lactic-co-glycolic) acid nanoparticles.

    PubMed

    Langert, Kelly A; Goshu, Bruktawit; Stubbs, Evan B

    2017-01-01

    Acute inflammatory demyelinating polyneuropathy (AIDP) is an aggressive antibody- and T-cell-mediated variant of Guillain-Barré Syndrome (GBS), a prominent and debilitating autoimmune disorder of the peripheral nervous system. Despite advancements in clinical management, treatment of patients with AIDP/GBS and its chronic variant CIDP remains palliative and relies on the use of non-specific immunemodulating therapies. Our laboratory has previously reported that therapeutic administration of statins safely attenuates the clinical severity of experimental autoimmune neuritis (EAN), a well-characterized animal model of AIDP/GBS, by restricting the migration of autoreactive leukocytes across peripheral nerve microvascular endoneurial endothelial cells that form the blood-nerve barrier. Despite these advancements, the clinical application of systemically administered statins for the management of inflammatory disorders remains controversial as a result of disappointingly inconclusive phase trials. Here, poly(lactic-co-glycolic) acid (PLGA) nanoparticles were evaluated as an alternative strategy by which to locally administer statins for the management of EAN. When tested in vitro, lovastatin-encapsulating PLGA nanoparticles elicited a marked increase in RhoB mRNA content in peripheral nerve microvascular endoneurial endothelial cells, similar to cells treated with activated unencapsulated lovastatin. Unilateral peri-neural administration of lovastatin-encapsulating PLGA nanoparticles, but not empty nanoparticles, to naïve Lewis rats similarly enhanced RhoB mRNA content in adjacent nerve and muscle tissue. When administered in this manner, serum levels of lovastatin were below the level of detection. Bilateral peri-neural administration of lovastatin-encapsulating PLGA nanoparticles to EAN-induced Lewis rats significantly attenuated EAN clinical severity while protecting against EAN-induced peripheral nerve morphological and functional deficits. This study provides

  19. Engineering a Light-Attenuating Artificial Iris

    PubMed Central

    Shareef, Farah J.; Sun, Shan; Kotecha, Mrignayani; Kassem, Iris; Azar, Dimitri; Cho, Michael

    2016-01-01

    Purpose Discomfort from light exposure leads to photophobia, glare, and poor vision in patients with congenital or trauma-induced iris damage. Commercial artificial iris lenses are static in nature to provide aesthetics without restoring the natural iris's dynamic response to light. A new photo-responsive artificial iris was therefore developed using a photochromic material with self-adaptive light transmission properties and encased in a transparent biocompatible polymer matrix. Methods The implantable artificial iris was designed and engineered using Photopia, a class of photo-responsive materials (termed naphthopyrans) embedded in polyethylene. Photopia was reshaped into annular disks that were spin-coated with polydimethylsiloxane (PDMS) to form our artificial iris lens of controlled thickness. Results Activated by UV and blue light in approximately 5 seconds with complete reversal in less than 1 minute, the artificial iris demonstrates graded attenuation of up to 40% of visible and 60% of UV light. There optical characteristics are suitable to reversibly regulate the incident light intensity. In vitro cell culture experiments showed up to 60% cell death within 10 days of exposure to Photopia, but no significant cell death observed when cultured with the artificial iris with protective encapsulation. Nuclear magnetic resonance spectroscopy confirmed these results as there was no apparent leakage of potentially toxic photochromic material from the ophthalmic device. Conclusions Our artificial iris lens mimics the functionality of the natural iris by attenuating light intensity entering the eye with its rapid reversible change in opacity and thus potentially providing an improved treatment option for patients with iris damage. PMID:27116547

  20. Ultrasonic attenuation in molecular crystals

    NASA Astrophysics Data System (ADS)

    Perrin, Bernard

    1981-11-01

    It is now well established from an experimental point of view that, concerning the ultrasonic attenuation, molecular crystals exhibit a specific behavior among dielectric crystals. This fact suggests the presence of a relaxation process. Liebermann, who has introduced this field, has proposed a way to analyze this problem and in particular has given an expression for the ultrasonic absorption coefficient in terms of a relaxation time and some thermodynamic quantities. In contrast to Liebermann's approach, a solid-state viewpoint is presented here, and it is shown that this ultrasonic relaxation can be taken into account in the framework of Akhieser's theory. A general expression of the ultrasonic absorption coefficient is calculated in terms of the phonon collision operator using the Boltzmann-equation approach of Woodruff and Ehrenreich. The collision-time approximation widely used in dielectric crystals fails in molecular crystals for which the presence of slow relaxation times in the collision operator prevents the thermalization of the whole set of phonons and gives rise to an ultrasonic relaxation. Thus a more suitable approximation is suggested here, which leads to a new expression of the ultrasonic attenuation valid in molecular crystals. Different forms of this expression are discussed, and comparison with Liebermann's expression used in most of the previous papers shows that the present treatment takes better account of the anisotropy of the solid state. The fit of experimental results obtained for some ionic-molecular crystals also shows that the expression derived here gives better agreement than does Liebermann's. Finally, it is shown that in the framework of the present treatment and under rather general conditions, the anisotropy affects primarily the magnitude of the ultrasonic absorption due to the molecular relaxation, but it does not affect its frequency dependence.

  1. DIVERGENCE, NOT DIVERSITY OF AN ATTENUATED EQUINE LENTIVIRUS VACCINE STRAIN CORRELATES WITH PROTECTION FROM DISEASE

    PubMed Central

    Craigo, Jodi K.; Barnes, Shannon; Cook, Sheila J.; Issel, Charles J.; Montelaro, Ronald C.

    2010-01-01

    We recently reported an attenuated EIAV vaccine study that directly examined the effect of lentiviral envelope sequence variation on vaccine efficacy. The study [1] demonstrated for the first time the failure of an ancestral vaccine to protect and revealed a significant, inverse, linear relationship between envelope divergence and protection from disease. In the current study we examine in detail the evolution of the attenuated vaccine strain utilized in this previous study. We demonstrate here that the attenuated strain progressively evolved during the six-month pre-challenge period and that the observed protection from disease was significantly associated with divergence from the original vaccine strain. PMID:20955830

  2. A GIS TECHNIQUE FOR ESTIMATING NATURAL ATTENUATION RATES AND MASS BALANCES

    EPA Science Inventory

    ABSTRACT: Regulatory approval of monitored natural attenuation (MNA) as a component for site remediation often requires a demonstration that contaminant mass has decreased significantly over time. Successful approval of MNA also typically requires an estimate of past and future n...

  3. Effects of medullary administration of a nitric oxide precursor on cardiovascular responses and neurotransmission during static exercise following ischemic stroke.

    PubMed

    Phattanarudee, Siripan; Towiwat, Pasarapa; Maher, Timothy J; Ally, Ahmmed

    2013-07-01

    We have reported that in rats with a 90 min left middle cerebral artery occlusion (MCAO) and 24 h reperfusion, pressor responses during muscle contractions were attenuated, as were glutamate concentrations in the left rostral ventrolateral medulla (RVLM) and left caudal VLM (CVLM), but gamma-aminobutyric acid (GABA) levels increased in left RVLM and CVLM. This study determined the effects of L-arginine, a nitric oxide (NO) precursor, within the RVLM and (or) CVLM on cardiovascular activity and glutamate/GABA levels during static exercise in left-sided MCAO rats. Microdialysis of L-arginine into left RVLM had a greater attenuation of cardiovascular responses, a larger decrease in glutamate, and a significant increase in GABA levels during muscle contractions in stroke rats. Administration of N(G)-monomethyl-L-arginine, an NO-synthase inhibitor, reversed the effects. In contrast, L-arginine administration into left CVLM evoked a greater potentiation of cardiovascular responses, increased glutamate, and decreased GABA levels during contractions in stroked rats. However, L-arginine administration into both left RVLM and left CVLM elicited responses similar to its infusion into the left RVLM. These results suggest that NO within the RVLM and CVLM modulates cardiovascular responses and glutamate/GABA neurotransmission during static exercise following stroke, and that a RVLM-NO mechanism has a dominant effect in the medullary regulation of cardiovascular function.

  4. Exposure to 1 ppm ozone attenuates the immediate antigenic response of canine peripheral airways

    SciTech Connect

    Kleeberger, S.R.; Kolbe, J.; Turner, C.; Spannhake, E.W. )

    1989-01-01

    The effect of oxidant exposure on the immediate airway response to immunologic challenge is controversial. We investigated the response of canine peripheral airways to antigen aerosol, 1-3 h and 24 h after a 5-min exposure to 1 ppm ozone. In dogs that were natively sensitive to Ascaris suum antigen, resistance to flow through the collateral system (Rcs) was measured using the wedged bronchoscope technique. In eight dogs, four sublobar segments of each lung were wedged: two were exposed to ozone for 5 min and two (control) received air with 5% CO2. Ozone caused a mean ( +/- SE) increase in Rcs of 75 +/- 15%, which returned to baseline after 1-3 h. The increase in Rcs elicited by subsequent administration of antigen aerosol (25 microliters, 0.27 mg protein/ml) to the ozone-exposed segments (312.0 +/- 70.6%) was attenuated by 22% compared to controls (398.9 +/- 83.0%; p less than .05). In another series of experiments (n = 5), segments were exposed to ozone or air and challenged with antigen 24 h later and a significant attenuation (38%) of the antigen-induced increase in Rcs was detected compared to controls (178.5 +/- 57.9 vs 289.0 +/- 62.2; p less than .05). Cellular influx of polymorphonuclear leukocytes (PMNs) was not detected by bronchoalveolar lavage (BAL) 1-3 h after ozone, but was found after 24 h (19.8 vs. 4.7%; p less than .01). A significant increase in PMNs was detected in exposed subepithelial tissues 1-3 h after ozone compared to unexposed tissues. Tissue PMNs were not significantly different from unexposed tissues after 24 h, but a shift toward degranulation of mast cells was detected in ozone-exposed tissues at this time. These data suggest that the Rcs response to antigen is attenuated 1-3 h and 24 h after acute (5 min) exposure to 1 ppm ozone, and this effect occurs independently of PMNs in the airways.

  5. Baicalin Attenuates IL-17-Mediated Acetaminophen-Induced Liver Injury in a Mouse Model

    PubMed Central

    Liao, Chia-Chih; Day, Yuan-Ji; Lee, Hung-Chen; Liou, Jiin-Tarng; Chou, An-Hsun; Liu, Fu-Chao

    2016-01-01

    Background IL-17 has been shown to be involved in liver inflammatory disorders in both mice and humans. Baicalin (BA), a major compound extracted from traditional herb medicine (Scutellariae radix), has potent hepatoprotective properties. Previous study showed that BA inhibits IL-17-mediated lymphocyte adhesion and downregulates joint inflammation. The aim of this study is to investigate the role of IL-17 in the hepatoprotective effects of BA in an acetaminophen (APAP)-induced liver injury mouse model. Methods Eight weeks male C57BL/6 (B6) mice were used for this study. Mice received intraperitoneal hepatotoxic injection of APAP (300 mg/kg) and after 30 min of injection, the mice were treated with BA at a concentration of 30 mg/kg. After 16 h of treatment, mice were killed. Blood samples and liver tissues were harvested for analysis of liver injury parameters. Results APAP overdose significantly increased the serum alanine transferase (ALT) levels, hepatic activities of myeloperoxidase (MPO), expression of cytokines (TNF-α, IL-6, and IL-17), and malondialdehyde (MDA) activity when compared with the control animals. BA treatment after APAP administration significantly attenuated the elevation of these parameters in APAP-induced liver injury mice. Furthermore, BA treatment could also decrease hepatic IL-17-producing γδT cells recruitment, which was induced after APAP overdose. Conclusion Our data suggested that baicalin treatment could effectively decrease APAP-induced liver injury in part through attenuation of hepatic IL-17 expression. These results indicate that baicalin is a potential hepatoprotective agent. PMID:27855209

  6. Zingiber officinale attenuates retinal microvascular changes in diabetic rats via anti-inflammatory and antiangiogenic mechanisms

    PubMed Central

    Dongare, Shirish; Mathur, Rajani; Saxena, Rohit; Mathur, Sandeep; Agarwal, Renu; Nag, Tapas C.; Srivastava, Sushma; Kumar, Pankaj

    2016-01-01

    Purpose Diabetic retinopathy is a common microvascular complication of long-standing diabetes. Several complex interconnecting biochemical pathways are activated in response to hyperglycemia. These pathways culminate into proinflammatory and angiogenic effects that bring about structural and functional damage to the retinal vasculature. Since Zingiber officinale (ginger) is known for its anti-inflammatory and antiangiogenic properties, we investigated the effects of its extract standardized to 5% 6-gingerol, the major active constituent of ginger, in attenuating retinal microvascular changes in rats with streptozotocin-induced diabetes. Methods Diabetic rats were treated orally with the vehicle or the ginger extract (75 mg/kg/day) over a period of 24 weeks along with regular monitoring of bodyweight and blood glucose and weekly fundus photography. At the end of the 24-week treatment, the retinas were isolated for histopathological examination under a light microscope, transmission electron microscopy, and determination of the retinal tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), and vascular endothelial growth factor (VEGF) levels. Results Oral administration of the ginger extract resulted in significant reduction of hyperglycemia, the diameter of the retinal vessels, and vascular basement membrane thickness. Improvement in the architecture of the retinal vasculature was associated with significantly reduced expression of NF-κB and reduced activity of TNF-α and VEGF in the retinal tissue in the ginger extract–treated group compared to the vehicle-treated group. Conclusions The current study showed that ginger extract containing 5% of 6-gingerol attenuates the retinal microvascular changes in rats with streptozotocin-induced diabetes through anti-inflammatory and antiangiogenic actions. Although precise molecular targets remain to be determined, 6-gingerol seems to be a potential candidate for further investigation. PMID:27293376

  7. Diabetes attenuates the inhibitory effects of endomorphin-2, but not endomorphin-1 on gastrointestinal transit in mice.

    PubMed

    Wang, Chang-lin; Diao, Yu-xiang; Xiang, Qiong; Ren, Yu-kun; Gu, Ning

    2014-09-05

    Diabetes affects the entire gastrointestinal tract from the esophagus to the anus. In the present study, the charcoal meal test was undertaken to evaluate and compare the effects of intracerebroventricular (i.c.v.) administration of endomorphins (EMs) on gastrointestinal transit in non-diabetic and diabetic mice. Significantly delayed gastrointestinal transit was found in both 4 and 8 weeks alloxan-induced diabetes compared to non-diabetes. Moreover, i.c.v. EM-1 and EM-2 dose-dependently delayed gastrointestinal transit in non-diabetes and diabetes. The EM-1-induced inhibitory effects of gastrointestinal transit in 4 weeks diabetes were qualitatively similar to those of non-diabetes. However, at higher doses, the EM-1-induced effects in 8 weeks diabetes were largely enhanced. Different to EM-1, the EM-2-induced inhibition of gastrointestinal transit in diabetic mice was significantly attenuated compared to non-diabetic mice. Moreover, these effects were further decreased in 8 weeks diabetes. The delayed gastrointestinal transit effects caused by EM-1 may be primarily mediated by μ2-opioid receptor in both non-diabetes and 4 weeks diabetes. Interestingly, in 8 weeks diabetes, these effects were mediated by μ2- and δ-receptors. However, the inhibitory effects of EM-2 were mediated by μ1-opioid receptor, which exerted a reduced function in diabetes. Also, poor blood glucose control might result in the attenuated effects of EM-2. Our present results demonstrated that diabetes attenuates the inhibitory effects of EM-2, but not EM-1 on gastrointestinal transit in mice. The different effects of EM-1 and EM-2 on gastrointestinal transit in diabetes may be due to changes of opioid receptor subtypes and their functional responses.

  8. A finite element simulation of sound attenuation in a finite duct with a peripherally variable liner

    NASA Technical Reports Server (NTRS)

    Watson, W. R.

    1977-01-01

    Using multimodal analysis, a variational finite element method is presented for analyzing sound attenuation in a three-dimensional finite duct with a peripherally variable liner in the absence of flow. A rectangular element, with cubic shaped functions, is employed. Once a small portion of a peripheral liner is removed, the attenuation rate near the frequency where maximum attenuation occurs drops significantly. The positioning of the liner segments affects the attenuation characteristics of the liner. Effects of the duct termination are important in the low frequency ranges. The main effect of peripheral variation of the liner is a broadening of the attenuation characteristics in the midfrequency range. Because of matrix size limitations of the presently available computer program, the eigenvalue equations should be solved out of core in order to handle realistic sources.

  9. Attenuation by d-limonene of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

    PubMed

    Yano, H; Tatsuta, M; Iishi, H; Baba, M; Sakai, N; Uedo, N

    1999-08-27

    The effects of prolonged administration of d-limonene, a monocyclic monoterpene, on sodium chloride-enhanced induction of gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine, the labeling and apoptotic indices, and ornithine decarboxylase (ODC) activity of gastric cancers were investigated in Wistar rats. After 25 weeks of carcinogen treatment, rats were given chow pellets containing 10% sodium chloride and 1% limonene ad libitum. In week 52, the incidence of gastric cancers, the labeling index and ODC activity were significantly higher and the apoptotic index was significantly lower in rats given sodium chlolide than in untreated control rats. However, in rats given both sodium chloride and d-limonene, the incidence of gastric cancers, the labeling index and ODC activity were significantly lower and the apoptotic index was significantly higher than in rats given sodium chloride alone. Our findings suggest that limonene attenuates the gastric carcinogenesis enhanced by sodium chloride via increased apoptosis and decreased ODC activity in gastric cancers.

  10. Effects of Chronic Buspirone Treatment on Cocaine Self-Administration

    PubMed Central

    Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J; Bergman, Jack

    2013-01-01

    Cocaine abuse and dependence is a major public health problem that continues to challenge medication-based treatment. Buspirone (Buspar) is a clinically available, non-benzodiazepine anxiolytic medication that acts on both serotonin and dopamine systems. In recent preclinical studies, acute buspirone treatment reduced cocaine self-administration at doses that did not also decrease food-reinforced behavior in rhesus monkeys (Bergman et al, 2012). The present study evaluated the effectiveness of chronic buspirone treatment on self-administration of cocaine and food. Five adult rhesus monkeys (Macaca mulatta) were trained to self-administer cocaine and food during four 1-h daily sessions under a second-order schedule of reinforcement (FR2 [VR 16:S]). Buspirone (0.32 and 0.56 mg/kg/h) was administered intravenously through one lumen of a double-lumen catheter every 20 min for 23 h each day for 7–10 consecutive days. Each buspirone treatment period was followed by saline control treatment until drug- and food-maintained responding returned to baseline levels. Buspirone significantly reduced responding maintained by cocaine, and shifted the dose–effect curve downwards. Buspirone had minimal effects on food-maintained responding. In cocaine discrimination studies, buspirone (0.1–0.32 mg/kg, IM) did not antagonize the discriminative stimulus and rate-altering effects of cocaine in four of six monkeys. These findings indicate that buspirone selectively attenuates the reinforcing effects of cocaine in a nonhuman primate model of cocaine self-administration, and has variable effects on cocaine discrimination. PMID:23072835

  11. Effects of chronic buspirone treatment on cocaine self-administration.

    PubMed

    Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J; Bergman, Jack

    2013-02-01

    Cocaine abuse and dependence is a major public health problem that continues to challenge medication-based treatment. Buspirone (Buspar) is a clinically available, non-benzodiazepine anxiolytic medication that acts on both serotonin and dopamine systems. In recent preclinical studies, acute buspirone treatment reduced cocaine self-administration at doses that did not also decrease food-reinforced behavior in rhesus monkeys (Bergman et al, 2012). The present study evaluated the effectiveness of chronic buspirone treatment on self-administration of cocaine and food. Five adult rhesus monkeys (Macaca mulatta) were trained to self-administer cocaine and food during four 1-h daily sessions under a second-order schedule of reinforcement (FR2 [VR 16:S]). Buspirone (0.32 and 0.56 mg/kg/h) was administered intravenously through one lumen of a double-lumen catheter every 20 min for 23 h each day for 7-10 consecutive days. Each buspirone treatment period was followed by saline control treatment until drug- and food-maintained responding returned to baseline levels. Buspirone significantly reduced responding maintained by cocaine, and shifted the dose-effect curve downwards. Buspirone had minimal effects on food-maintained responding. In cocaine discrimination studies, buspirone (0.1-0.32 mg/kg, IM) did not antagonize the discriminative stimulus and rate-altering effects of cocaine in four of six monkeys. These findings indicate that buspirone selectively attenuates the reinforcing effects of cocaine in a nonhuman primate model of cocaine self-administration, and has variable effects on cocaine discrimination.

  12. The contribution of activated processes to Q. [stress corrosion cracking in seismic wave attenuation

    NASA Technical Reports Server (NTRS)

    Spetzler, H. A.; Getting, I. C.; Swanson, P. L.

    1980-01-01

    The possible role of activated processes in seismic attenuation is investigated. In this study, a solid is modeled by a parallel and series configuration of dashpots and springs. The contribution of stress and temperature activated processes to the long term dissipative behavior of this system is analyzed. Data from brittle rock deformation experiments suggest that one such process, stress corrosion cracking, may make a significant contribution to the attenuation factor, Q, especially for long period oscillations under significant tectonic stress.

  13. LONG TERM MONITORING FOR NATURAL ATTENUATION

    EPA Science Inventory

    We have good statistical methods to: (1) determine whether concentrations of a contaminant are attenuating over time, (2) determine the rate of attenuation and confidence interval on the rate, and (3) determine whether concentrations have met a particular clean up goal. We do no...

  14. On the level-dependent attenuation of a perforated device.

    PubMed

    Chen, Lan; Sang, Jinqiu; Li, Xiaodong

    2009-05-01

    To investigate the physical principle governing the level-dependent attenuation of a perforated earplug, a mathematical model is first established with the transfer-matrix method to calculate the noise reduction through a simplified device, one perforated panel with back cavity, mounted in an impedance tube. The model prediction is compared with the measured noise reduction through two series of large-scale devices and one device with the dimensions of the ear canal under continuous noise and sinusoidal excitations. The model helps to improve significantly the level-dependent attenuation of the large-scale device. It also illustrates that the attenuation is not solely determined by the resistance of the orifice, which has been a well accepted design concept, but resulted from an incorporated effect of the acoustic filter comprised of the acoustic impedance of the orifice and other elements in the earplug-ear-canal system. This mechanism can interpret a resonance at low incident levels on improper design and reveal approaches to eliminate it. Finally, the model's potential contributions to the design of a perforated earplug are discussed, along with the threshold of level-dependent attenuation supported with experimental evidence.

  15. Low-energy gamma ray attenuation characteristics of aviation fuels

    NASA Technical Reports Server (NTRS)

    Singh, Jag J.; Shen, Chih-Ping; Sprinkle, Danny R.

    1990-01-01

    Am241 (59.5 keV) gamma ray attenuation characteristics were investigated in 270 aviation fuel (Jet A and Jet A-1) samples from 76 airports around the world as a part of world wide study to measure the variability of aviation fuel properties as a function of season and geographical origin. All measurements were made at room temperature which varied from 20 to 27 C. Fuel densities (rho) were measured concurrently with their linear attenuation coefficients (mu), thus providing a measure of mass attenuation coefficient (mu/rho) for the test samples. In 43 fuel samples, rho and mu values were measured at more than one room temperature, thus providing mu/rho values for them at several temperatures. The results were found to be independent of the temperature at which mu and rho values were measured. It is noted that whereas the individual mu and rho values vary considerably from airport to airport as well as season to season, the mu/rho values for all samples are constant at 0.1843 + or - 0.0013 cu cm/gm. This constancy of mu/rho value for aviation fuels is significant since a nuclear fuel quantity gauging system based on low energy gamma ray attenuation will be viable throughout the world.

  16. Ursodeoxycholic acid attenuates colonic epithelial secretory function

    PubMed Central

    Kelly, Orlaith B; Mroz, Magdalena S; Ward, Joseph B J; Colliva, Carolina; Scharl, Michael; Pellicciari, Roberto; Gilmer, John F; Fallon, Padraic G; Hofmann, Alan F; Roda, Aldo; Murray, Frank E; Keely, Stephen J

    2013-01-01

    Dihydroxy bile acids, such as chenodeoxycholic acid (CDCA), are well known to promote colonic fluid and electrolyte secretion, thereby causing diarrhoea associated with bile acid malabsorption. However, CDCA is rapidly metabolised by colonic bacteria to ursodeoxycholic acid (UDCA), the effects of which on epithelial transport are poorly characterised. Here, we investigated the role of UDCA in the regulation of colonic epithelial secretion. Cl− secretion was measured across voltage-clamped monolayers of T84 cells and muscle-stripped sections of mouse or human colon. Cell surface biotinylation was used to assess abundance/surface expression of transport proteins. Acute (15 min) treatment of T84 cells with bilateral UDCA attenuated Cl− secretory responses to the Ca2+ and cAMP-dependent secretagogues carbachol (CCh) and forskolin (FSK) to 14.0 ± 3.8 and 40.2 ± 7.4% of controls, respectively (n= 18, P < 0.001). Investigation of the molecular targets involved revealed that UDCA acts by inhibiting Na+/K+-ATPase activity and basolateral K+ channel currents, without altering their cell surface expression. In contrast, intraperitoneal administration of UDCA (25 mg kg−1) to mice enhanced agonist-induced colonic secretory responses, an effect we hypothesised to be due to bacterial metabolism of UDCA to lithocholic acid (LCA). Accordingly, LCA (50–200 μm) enhanced agonist-induced secretory responses in vitro and a metabolically stable UDCA analogue, 6α-methyl-UDCA, exerted anti-secretory actions in vitro and in vivo. In conclusion, UDCA exerts direct anti-secretory actions on colonic epithelial cells and metabolically stable derivatives of the bile acid may offer a new approach for treating intestinal diseases associated with diarrhoea. PMID:23507881

  17. Central administration of metastin increases food intake through opioid neurons in chicks.

    PubMed

    Khan, Md Sakirul Islam; Ohkubo, Takeshi; Masuda, Naoto; Tachibana, Tetsuya; Ueda, Hiroshi

    2009-06-01

    Metastin, an RFamide peptide, has been isolated from human placenta and possesses several physiological actions in mammals. However, little is known about this bioactive peptide in avian species. This study was conducted to assess the effect of metastin on feeding behavior of chicks (Gallus gallus). The food intake of chicks is significantly increased by the intracerebroventricular injection of metastin. Beta-funaltrexamine, a mu-opioid receptor antagonist, significantly attenuates metastin-induced food intake in chicks. In contrast, delta- and kappa-opioid receptor antagonists did not show any influence on metastin-induced food intake in chicks. In addition, administration of N(G)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, did not influence metastin-induced food intake. Taken together, this study shows the orexigenic effect of metastin in chicks and suggests that this effect is mediated by mu-opioid receptor.

  18. Behavioral consequences of chelator administration in acute cadmium toxicity (journal version)

    SciTech Connect

    Peele, D.B.; Farmer, J.D.; MacPhail, R.C.

    1988-01-01

    The conditioned flavor-aversion paradigm was used to assess the toxicity of acutely administered cadmium and the interaction of cadmium with the heavy-metal chelating agents dimercaprol (BAL) and dimercaptosuccinic acid (DMSA). Shortly after consuming saccharin, rats received cadmium either alone or in combination with BAL or DMSA. When compared to rats receiving either nothing or the vehicle, rats receiving cadmium displayed significant reductions in saccharin preference (i.e., conditioned flavor aversions). BAL and DMSA were also capable of producing conditioned flavor aversions when given alone. Rats receiving cadmium in combination with either BAL or DMSA displayed significant, but not complete, attenuations of conditioned flavor aversions when compared to rats receiving cadmium alone. Chelator-induced blockade of cadmium-induced flavor-aversion conditioning was not obtained when BAL or DMSA administration was delayed by 4 hrs.

  19. The selective dopamine D₃ receptor antagonist SB-277011A attenuates drug- or food-deprivation reactivation of expression of conditioned place preference for cocaine in male Sprague-Dawley rats.

    PubMed

    Ashby, Charles R; Rice, Onarae V; Heidbreder, Christian A; Gardner, Eliot L

    2015-06-01

    We determined the effect of the selective dopamine D3 receptor antagonist SB-277011A on reactivation of conditioned place preference (CPP) to cocaine elicited by priming injections of cocaine or exposure to food deprivation stress (21 h) in male Sprague-Dawley rats. Animals paired with the cocaine-associated chamber displayed a robust and consistent CPP response. This CPP was extinguished after repeated pairings of the conditioned stimuli (cocaine-paired chamber contextual cues) in the absence of the unconditioned stimulus (cocaine). Twenty-four hours later, the administration of 5 mg kg(-1) i.p. of cocaine (immediately before the test) or exposure to 21 h of food deprivation reactivated the expression of the cocaine-induced CPP. In contrast, administration of 1 ml kg(-1) i.p. of vehicle did not reactivate the CPP response. Administration of the selective dopamine D3 receptor antagonist SB-277011A (3-24 mg kg(-1) i.p.) 30 min before cocaine administration on the test day produced a significant attenuation of CPP reactivation. Reactivation of the CPP response produced by food deprivation was also significantly attenuated by SB-277011A (6 or 12 mg kg(-1) i.p.) given 30 min before the test session. SB-277011A (12 or 24 mg kg(-1) i.p.) did not itself produce reactivation of the CPP response. Overall, these results suggest that the reactivation of the incentive value of drug-associated cues by cocaine or food deprivation is attenuated by selective antagonism of D3 receptors.

  20. N-acetyl-cysteine attenuates neuropathic pain by suppressing matrix metalloproteinases.

    PubMed

    Li, Jiajie; Xu, Lujie; Deng, Xueting; Jiang, Chunyi; Pan, Cailong; Chen, Lu; Han, Yuan; Dai, Wenling; Hu, Liang; Zhang, Guangqin; Cheng, Zhixiang; Liu, Wentao

    2016-08-01

    The treatment of neuropathic pain remains a clinical challenge because of its unclear mechanisms and broad clinical morbidity. Matrix metalloproteinase (MMP)-9 and MMP-2 have previously been described as key components in neuropathic pain because of their facilitation of inflammatory cytokine maturation and induction of neural inflammation. Therefore, the inhibition of MMPs may represent a novel therapeutic approach to the treatment of neuropathic pain. In this study, we report that N-acetyl-cysteine (NAC), which is a broadly used respiratory drug, significantly attenuates neuropathic pain through a unique mechanism of MMP inhibition. Both the in vitro (0.1 mM) and in vivo application of NAC significantly suppressed the activity of MMP-9/2. Orally administered NAC (50, 100, and 200 mg/kg) not only postponed the occurrence but also inhibited the maintenance of chronic constrictive injury (CCI)-induced neuropathic pain in rats. The administration of NAC blocked the maturation of interleukin-1β, which is a critical substrate of MMPs, and markedly suppressed the neuronal activation induced by CCI, including inhibiting the phosphorylation of protein kinase Cγ, NMDAR1, and mitogen-activated protein kinases. Finally, NAC significantly inhibited CCI-induced microglia activation but elicited no notable effects on astrocytes. These results demonstrate an effective and safe approach that has been used clinically to alleviate neuropathic pain through the powerful inhibition of the activation of MMPs.

  1. Myoinositol Attenuates the Cell Loss and Biochemical Changes Induced by Kainic Acid Status Epilepticus

    PubMed Central

    Kikvidze, Marina

    2016-01-01

    Identification of compounds preventing or modifying the biochemical changes that underlie the epileptogenesis process and understanding the mechanism of their action are of great importance. We have previously shown that myoinositol (MI) daily treatment for 28 days prevents certain biochemical changes that are triggered by kainic acid (KA) induced status epilepticus (SE). However in these studies we have not detected any effects of MI on the first day after SE. In the present study we broadened our research and focused on other molecular and morphological changes at the early stages of SE induced by KA and effects of MI treatment on these changes. The increase in the amount of voltage-dependent anionic channel-1 (VDAC-1), cofilin, and caspase-3 activity was observed in the hippocampus of KA treated rats. Administration of MI 4 hours later after KA treatment abolishes these changes, whereas diazepam treatment by the same time schedule has no significant influence. The number of neuronal cells in CA1 and CA3 subfields of hippocampus is decreased after KA induced SE and MI posttreatment significantly attenuates this reduction. No significant changes are observed in the neocortex. Obtained results indicate that MI posttreatment after KA induced SE could successfully target the biochemical processes involved in apoptosis, reduces cell loss, and can be successfully used in the future for translational research. PMID:27642592

  2. Targeted Inhibition of Complement Using Complement Receptor 2-Conjugated Inhibitors Attenuates EAE

    PubMed Central

    Hu, Xianzhen; Tomlinson, Stephen; Barnum, Scott R.

    2012-01-01

    Multiple sclerosis (MS) is the most common autoimmune demyelinating disease, affecting millions of individuals worldwide. In the last two decades, many therapeutic options for the treatment of MS have become available, however they are limited in terms of effectiveness and some remain plagued by safety issues. The currently available treatment options target relapsing remitting forms of MS and are not effective against the more progressive forms of the disease. These limitations highlight a significant unmet treatment need for MS. In experimental autoimmune encephalomyelitis (EAE) studies from our laboratory, we have previously shown, using a number of complement mutant and transgenic mice, that inhibition of the alternative complement pathway and the C3 convertase confers significant protection from disease. We report here that targeted inhibition of complement activation using complement receptor 2 (CR2)-conjugated inhibitors significantly attenuates EAE. Administration of CR2-Crry (blocks all complement pathways at C3 activation) and CR2-fH (specifically blocks the alternative pathway) just prior to and during the onset of EAE blocks progression of both acute and chronic disease. These data indicate that inhibition of complement may offer an effective therapeutic approach to treating both acute and chronic forms of demyelinating disease through blocking the alternative pathway or complement convertases. PMID:23079547

  3. Targeted inhibition of complement using complement receptor 2-conjugated inhibitors attenuates EAE.

    PubMed

    Hu, Xianzhen; Tomlinson, Stephen; Barnum, Scott R

    2012-11-30

    Multiple sclerosis (MS) is the most common autoimmune demyelinating disease, affecting millions of individuals worldwide. In the last two decades, many therapeutic options for the treatment of MS have become available, however they are limited in terms of effectiveness and some remain plagued by safety issues. The currently available treatment options target relapsing remitting forms of MS and are not effective against the more progressive forms of the disease. These limitations highlight a significant unmet treatment need for MS. In experimental autoimmune encephalomyelitis (EAE) studies from our laboratory, we have previously shown, using a number of complement mutant and transgenic mice, that inhibition of the alternative complement pathway and the C3 convertase confers significant protection from disease. We report here that targeted inhibition of complement activation using complement receptor 2 (CR2)-conjugated inhibitors significantly attenuates EAE. Administration of CR2-Crry (blocks all complement pathways at C3 activation) and CR2-fH (specifically blocks the alternative pathway) just prior to and during the onset of EAE blocks progression of both acute and chronic disease. These data indicate that inhibition of complement may offer an effective therapeutic approach to treating both acute and chronic forms of demyelinating disease through blocking the alternative pathway or complement convertases.

  4. Veterans Administration Databases

    Cancer.gov

    The Veterans Administration Information Resource Center provides database and informatics experts, customer service, expert advice, information products, and web technology to VA researchers and others.

  5. Evidence of 1,4-dioxane attenuation at groundwater sites contaminated with chlorinated solvents and 1,4-dioxane.

    PubMed

    Adamson, David T; Anderson, R Hunter; Mahendra, Shaily; Newell, Charles J

    2015-06-02

    There is a critical need to develop appropriate management strategies for 1,4-dioxane (dioxane) due to its widespread occurrence and perceived recalcitrance at groundwater sites where chlorinated solvents are present. A comprehensive evaluation of California state (GeoTracker) and Air Force monitoring records was used to provide significant evidence of dioxane attenuation at field sites. Temporal changes in the site-wide maximum concentrations were used to estimate source attenuation rates at the GeoTracker sites (median length of monitoring period = 6.8 years). While attenuation could not be established at all sites, statistically significant positive attenuation rates were confirmed at 22 sites. At sites where dioxane and chlorinated solvents were present, the median value of all statistically significant dioxane source attenuation rates (equivalent half-life = 31 months; n = 34) was lower than 1,1,1-trichloroethane (TCA) but similar to 1,1-dichloroethene (1,1-DCE) and trichloroethene (TCE). Dioxane attenuation rates were positively correlated with rates for 1,1-DCE and TCE but not TCA. At this set of sites, there was little evidence that chlorinated solvent remedial efforts (e.g., chemical oxidation, enhanced bioremediation) impacted dioxane attenuation. Attenuation rates based on well-specific records from the Air Force data set confirmed significant dioxane attenuation (131 out of 441 wells) at a similar frequency and extent (median equivalent half-life = 48 months) as observed at the California sites. Linear discriminant analysis established a positive correlation between dioxane attenuation and increasing concentrations of dissolved oxygen, while the same analysis found a negative correlation with metals and CVOC concentrations. The magnitude and prevalence of dioxane attenuation documented here suggest that natural attenuation may be used to manage some but not necessarily all dioxane-impacted sites.

  6. Attenuation of monkeypox virus by deletion of genomic regions

    USGS Publications Warehouse

    Lopera, Juan G.; Falendysz, Elizabeth A.; Rocke, Tonie E.; Osorio, Jorge E.

    2015-01-01

    Monkeypox virus (MPXV) is an emerging pathogen from Africa that causes disease similar to smallpox. Two clades with different geographic distributions and virulence have been described. Here, we utilized bioinformatic tools to identify genomic regions in MPXV containing multiple virulence genes and explored their roles in pathogenicity; two selected regions were then deleted singularly or in combination. In vitro and in vivostudies indicated that these regions play a significant role in MPXV replication, tissue spread, and mortality in mice. Interestingly, while deletion of either region led to decreased virulence in mice, one region had no effect on in vitro replication. Deletion of both regions simultaneously also reduced cell culture replication and significantly increased the attenuation in vivo over either single deletion. Attenuated MPXV with genomic deletions present a safe and efficacious tool in the study of MPX pathogenesis and in the identification of genetic factors associated with virulence.

  7. CT-based attenuation and scatter correction compared with uniform attenuation correction in brain perfusion SPECT imaging for dementia

    NASA Astrophysics Data System (ADS)

    Gillen, Rebecca; Firbank, Michael J.; Lloyd, Jim; O'Brien, John T.

    2015-09-01

    This study investigated if the appearance and diagnostic accuracy of HMPAO brain perfusion SPECT images could be improved by using CT-based attenuation and scatter correction compared with the uniform attenuation correction method. A cohort of subjects who were clinically categorized as Alzheimer’s Disease (n=38 ), Dementia with Lewy Bodies (n=29 ) or healthy normal controls (n=30 ), underwent SPECT imaging with Tc-99m HMPAO and a separate CT scan. The SPECT images were processed using: (a) correction map derived from the subject’s CT scan or (b) the Chang uniform approximation for correction or (c) no attenuation correction. Images were visually inspected. The ratios between key regions of interest known to be affected or spared in each condition were calculated for each correction method, and the differences between these ratios were evaluated. The images produced using the different corrections were noted to be visually different. However, ROI analysis found similar statistically significant differences between control and dementia groups and between AD and DLB groups regardless of the correction map used. We did not identify an improvement in diagnostic accuracy in images which were corrected using CT-based attenuation and scatter correction, compared with those corrected using a uniform correction map.

  8. Gleditsia sinensis Thorn Attenuates the Collagen-Based Migration of PC3 Prostate Cancer Cells through the Suppression of α2β1 Integrin Expression.

    PubMed

    Ryu, Sujin; Park, Ki Moon; Lee, Seung Ho

    2016-03-02

    Gleditsia sinensis thorns (GST) have been used as a traditional medicine for carbuncles and skin diseases. The purpose of this study was to decide whether non-toxicological levels of water extract of GST (WEGST) are effective in inhibiting the progress of prostate cancer formation and to identify the target molecule involved in the WEGST-mediated inhibitory process of prostate cancer cell migration and in vivo tumor formation. Through the Boyden chamber migration assay, we found that non-toxic levels of WEGST could not attenuate the PC3 migration to the bottom area coated with serum but significantly inhibited PC3 cell migration to the collagen-coated bottom area. We also found that non-toxic levels of WEGST significantly attenuated collagen against adhesion. Interestingly, ectopic administration of WEGST could not affect the expression of α2β1 integrin, which is known as a receptor of collagen. However, when the PC3 cells adhered to a collagen-coated plate, the expression of α2 integrin but not that of β1 integrin was significantly inhibited by the administration of non-toxic levels of WEGST, leading to the inhibition of focal adhesion kinase (FAK) phosphorylation. Furthermore, oral administration of WEGST (25 mg/kg/day) significantly inhibited the size of a PC3 cell-xenografted tumor. Taken together, these results suggest a novel molecular mechanism for WEGST to inhibit prostate cancer progression at particular stages, such as collagen-mediated adhesion and migration, and it might provide further development for the therapeutic use of WEGST in the treatment of prostate cancer progression.

  9. Acetate supplementation attenuates lipopolysaccharide-induced neuroinflammation.

    PubMed

    Reisenauer, Chris J; Bhatt, Dhaval P; Mitteness, Dane J; Slanczka, Evan R; Gienger, Heidi M; Watt, John A; Rosenberger, Thad A

    2011-04-01

    Glyceryl triacetate (GTA), a compound effective at increasing circulating and tissue levels of acetate was used to treat rats subjected to a continual 28 day intra-ventricular infusion of bacterial lipopolysaccharide (LPS). This model produces a neuroinflammatory injury characterized by global neuroglial activation and a decrease in choline acetyltransferase immunoreactivity in the basal forebrain. During the LPS infusion, rats were given a daily treatment of either water or GTA at a dose of 6 g/kg by oral gavage. In parallel experiments, free-CoA and acetyl-CoA levels were measured in microwave fixed brains and flash frozen heart, liver, kidney and muscle following a single oral dose of GTA. We found that a single oral dose of GTA significantly increased plasma acetate levels by 15 min and remained elevated for up to 4 h. At 30 min the acetyl-CoA levels in microwave-fixed brain and flash frozen heart and liver were increased at least 2.2-fold. The concentrations of brain acetyl-CoA was significantly increased between 30 and 45 min following treatment and remained elevated for up to 4 h. The concentration of free-CoA in brain was significantly decreased compared to controls at 240 min. Immunohistochemical and morphological analysis demonstrated that a daily treatment with GTA significantly reduced the percentage of reactive glial fibrillary acidic protein-positive astrocytes and activated CD11b-positive microglia by 40-50% in rats subjected to LPS-induced neuroinflammation. Further, in rats subjected to neuroinflammation, GTA significantly increased the number of choline acetyltransferase (ChAT)-positive cells by 40% in the basal forebrain compared to untreated controls. These data suggest that acetate supplementation increases intermediary short chain acetyl-CoA metabolism and that treatment is potentially anti-inflammatory and neuroprotective with regards to attenuating neuroglial activation and increasing ChAT immunoreactivity in this model.

  10. Curcumin Attenuates Hepatotoxicity Induced by Zinc Oxide Nanoparticles in Rats

    PubMed Central

    Khorsandi, Layasadat; Mansouri, Esrafil; Orazizadeh, Mahmoud; Jozi, Zahra

    2016-01-01

    Background: Zinc oxide nanoparticles (NZnO) are increasingly used in modern life. Most metal nanoparticles have adverse effects on the liver. Aims: To explore the protective action of curcumin (Cur) against hepatotoxicity induced by NZnO in rats. Study Design: Animal experimentation. Methods: Control group animals received normal saline, while the Cur group animals were treated with 200 mg/kg of Cur orally for 21 days. NZnO-intoxicated rats received 50 mg/kg of NZnO for 14 days by gavage method. In the NZnO+Cur group, rats were pretreated with Cur for 7 days before NZnO administration. Plasma activities of Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were measured as biomarkers of hepatotoxicity. Hepatic levels of malondialdehyde (MDA) and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured for detection of oxidative stress in liver tissue. Histological changes and apoptosis in liver tissue were studied by using Hematoxylin-eosin staining and the transferase dUTP nick end labeling (TUNEL) method. Results: NZnO induced a significant increase in plasma AST (2.8-fold), ALT (2.7-fold) and ALP (1.97-fold) activity in comparison to the control group (p<0.01). NZnO increased MDA content and reduced SOD and GPx activities. NZnO caused liver damage including centrilobular necrosis and microvesicular steatosis. The percentage of apoptosis in hepatocytes was increased in NZnO-treated rats (p<0.01). Pre-treatment of Cur significantly reduced lipid peroxidation (39%), increased SOD (156%) and GPx (26%) activities, and attenuated ALT (47%), AST (41%) and ALP (30%) activities. Pre-treatment with Cur also decreased the histology changes and apoptotic index of hepatocytes (p<0.05). Conclusion: These findings indicate that Cur effectively protects against NZnO-induced hepatotoxicity in rats. However, future studies are required to propose Cur as a potential protective agent against hepatotoxicity

  11. Preventive and Therapeutic Euphol Treatment Attenuates Experimental Colitis in Mice

    PubMed Central

    Bento, Allisson F.; Marcon, Rodrigo; Schmidt, Éder C.; Bouzon, Zenilda L.; Pianowski, Luiz F.; Calixto, João B.

    2011-01-01

    Background The tetracyclic triterpene euphol is the main constituent found in the sap of Euphorbia tirucalli. This plant is widely known in Brazilian traditional medicine for its use in the treatment of several kinds of cancer, including leukaemia, prostate and breast cancers. Here, we investigated the effect of euphol on experimental models of colitis and the underlying mechanisms involved in its action. Methodology/Principal Findings Colitis was induced in mice either with dextran sulfate sodium (DSS) or with 2,4,6-trinitrobenzene sulfonic acid (TNBS), and the effect of euphol (3, 10 and 30 mg/kg) on colonic injury was assessed. Pro-inflammatory mediators and cytokines were measured by immunohistochemistry, enzyme-Linked immunoabsorbent assay (ELISA), real time-polymerase chain reaction (RT-PCR) and flow cytometry. Preventive and therapeutic oral administration of euphol attenuated both DSS- and TNBS-induced acute colitis as observed by a significant reduction of the disease activity index (DAI), histological/microscopic damage score and myeloperoxidase (MPO) activity in colonic tissue. Likewise, euphol treatment also inhibited colon tissue levels and expression of IL-1β, CXCL1/KC, MCP-1, MIP-2, TNF-α and IL-6, while reducing NOS2, VEGF and Ki67 expression in colonic tissue. This action seems to be likely associated with inhibition of activation of nuclear factor-κB (NF-κB). In addition, euphol decreased LPS-induced MCP-1, TNF-α, IL-6 and IFN-γ, but increased IL-10 secretion from bone marrow-derived macrophages in vitro. Of note, euphol, at the same schedule of treatment, markedly inhibited both selectin (P- and E-selectin) and integrin (ICAM-1, VCAM-1 and LFA-1) expression in colonic tissue. Conclusions/Significance Together, these results clearly demonstrated that orally-administered euphol, both preventive or therapeutic treatment were effective in reducing the severity of colitis in two models of chemically-induced mouse colitis and suggest this plant

  12. Blocking PAR2 attenuates oxaliplatin-induced neuropathic pain via TRPV1 and releases of substance P and CGRP in superficial dorsal horn of spinal cord.

    PubMed

    Chen, Kun; Zhang, Zhi-Fa; Liao, Ming-Feng; Yao, Wen-Long; Wang, Juan; Wang, Xue-Ren

    2015-05-15

    Oxaliplatin (OXL) is a third-generation chemotherapeutic agent commonly used to treat metastatic digestive tumors; however, neuropathic pain is one of the main limiting complications of OXL. The purpose of this study was to examine the underlying mechanisms by which neuropathic pain is induced by OXL in a rat model. Our results demonstrated that blocking spinal proteinase-activated receptor 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) attenuated pain responses evoked by mechanical stimulation and decreased the releases of substance P and CGRP in the superficial dorsal horn of the spinal cord. The attenuating effect on mechanical pain was significantly smaller in OXL-rats than that in control rats. Blocking PAR2 also attenuated a heightened cold sensitivity evoked by OXL; whereas blocking TRPV1 had little effects on OXL-evoked hypersensitive cold response. Our data also showed that OXL increased the protein expressions of PAR2 and TRPV1 in the superficial dorsal horn. In addition, blocking PAR2 decreased TRPV1 expression in OXL-rats. Overall, our data suggest that upregulated expression of PAR2 in the superficial dorsal horn contributes to mechanical hyperalgesia and cold hypersensitivity; whereas amplified TRPV1 plays a role in regulating mechanical hyperalgesia, but not cold hypersensitivity after administration of OXL. We further suggest that TRPV1 is likely one of the signaling pathways for PAR2 to play a role in regulating OXL-induced neuropathic pain.

  13. Effect of subcutaneous administration of calcium channel blockers on nerve injury-induced hyperalgesia.

    PubMed

    White, D M; Cousins, M J

    1998-08-10

    Recent studies suggest that calcium contributes to peripheral neural mechanisms of hyperalgesia associated with nerve damage. In this animal behavioural study, we examined further the contribution of calcium in neuropathic pain by testing whether subcutaneous administration of either a calcium chelating agent or voltage-dependent calcium channel blockers attenuate nerve injury-induced hyperalgesia to mechanical stimulation. Studies were carried out in animals with partially ligated sciatic nerves, an established animal model of neuropathic pain. The nociceptive flexion reflex was quantified using an Ugo Basile Analgesymeter. Partial nerve injury induced a significant decrease in mechanical threshold compared to the sham operated controls. Daily subcutaneous injections of the calcium chelating agent, Quin 2 (20 microgram/2.5 microliter), significantly attenuated the nerve injury-induced hyperalgesia. Similarly, SNX-111, a N-type channel blocker, also significantly attenuated the nerve injury-induced hyperalgesia. SNX-230, a P and/or Q-type channel blocker, and nifedipine, a L-type channel blocker, had no effect on the hyperalgesia to mechanical stimulation. In control experiments, SNX-111 had no effect on mechanical thresholds when administered subcutaneously in either the hindpaw of normal animals or the back of the neck in nerve injury animals. This study shows that neuropathic pain involves a local calcium-dependent mechanism in the receptive field of intact neurons of an injured nerve, since it can be alleviated by subcutaneous injections of either a calcium chelating agent or SNX-111, a N-type calcium channel blocker. These agents may be effective, peripherally acting therapeutic agents for neuropathic pain.

  14. Role of p38 MAPK pathway in 17β-estradiol-mediated attenuation of hemorrhagic shock-induced hepatic injury.

    PubMed

    Hsu, Jun-Te; Chen, Tsung-Hsing; Chiang, Kun-Chun; Kuo, Chia-Jung; Lin, Chun-Jung; Yeh, Ta-Sen

    2015-01-15

    Although 17β-estradiol (E2) treatment following hemorrhagic shock or ischemic reperfusion prevents organs from dysfunction and injury, the precise mechanism remains unknown. We hypothesize that the E2-mediated attenuation of liver injury following hemorrhagic shock and fluid resuscitation occurs via the p38 mitogen-activated protein kinase (MAPK)-dependent heme oxygenase (HO)-1 pathway. After a 5-cm midline laparotomy, male rats underwent hemorrhagic shock (mean blood pressure ∼40 mmHg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, E2 (1 mg/kg) alone, or E2 plus p38 MAPK inhibitor SB-203580 (2 mg/kg), HO-1 inhibitor chromium mesoporphyrin-IX chloride (2.5 mg/kg) or estrogen receptor antagonist ICI 182,780 (3 mg/kg). At 2 h after hemorrhagic shock and fluid resuscitation, the liver injury markers were significantly increased compared with sham-operated control. Hemorrhagic shock resulted in a significant decrease in p38 MAPK phosphorylation compared with the shams. Administration of E2 following hemorrhagic shock normalized liver p38 MAPK phosphorylation, further increased HO-1 expression, and reduced cleaved caspase-3 levels. Coadministration of SB-203580 abolished the E2-mediated attenuation of the shock-induced liver injury markers. In addition, administration of chromium mesoporphyrin-IX chloride or ICI 182,780 abolished E2-mediated increases in liver HO-1 expression or p38 MAPK activation following hemorrhagic shock. Our results collectively suggest that the salutary effects of E2 on hepatic injury following hemorrhagic shock and resuscitation are in part mediated through an estrogen-receptor-related p38 MAPK-dependent HO-1 upregulation.

  15. Hypothermic anesthesia attenuates postoperative proteolysis.

    PubMed Central

    Johnson, D J; Brooks, D C; Pressler, V M; Hulton, N R; Colpoys, M F; Smith, R J; Wilmore, D W

    1986-01-01

    The catabolic response that commonly occurs after major operation is characterized by net skeletal muscle proteolysis and accelerated nitrogen excretion. This response was absent in patients undergoing cardiac surgical procedures associated with the combination of cardiopulmonary bypass, narcotic anesthesia, neuromuscular blockade, and hypothermia. Forearm nitrogen release was 422 +/- 492 nmol/100 ml X min on the first postoperative day, approximately 25% of preoperative values (1677 +/- 411, p less than 0.05). Nitrogen excretion and the degree of negative nitrogen balance were comparable to levels observed in nonstressed, fasting subjects. The potential role of hypothermia, high-dose fentanyl anesthesia, and neuromuscular blockade in modifying the catabolic response to laparotomy and retroperitoneal dissection was further evaluated in animal studies. Six hours after operation, amino acid nitrogen release from the hindquarter was 84% less than control values (p less than 0.05). Nitrogen excretion and urea production were also reduced compared to normothermic controls. It is concluded that the combination of hypothermia, narcotic anesthesia, and neuromuscular blockade attenuates the catabolic response to injury and thus may be useful in the care of critically ill surgical patients. PMID:3767477

  16. Nitrogen narcosis attenuates shivering thermogenesis.

    PubMed

    Mekjavić, I B; Savić, S A; Eiken, O

    1995-06-01

    Thermoregulatory responses of eight healthy subjects (six men and two women) were compared when they were head-out immersed in 15 degrees C water at both 1 and 6 ATA. Both trials were conducted in a hyperbaric chamber. During the immersions, esophageal temperature (T(es)) and skin temperature at two sites (chest and calf) were recorded at minute intervals. Oxygen uptake was determined at 5-min intervals with the Douglas bag method. The order of the two trials was alternated. The rate of T(es) cooling was greater during the 6-ATA trial [2.1 +/- 0.5 degrees C/h (SE)] than during the 1-ATA trial (1.3 +/- 0.5 degrees C/h; P < 0.01). Despite the greater rate of core cooling, and presumably a greater thermal drive for shivering, the oxygen uptake response for a similar decrement in T(es) was lower during exposure to 6 than to 1 ATA (P < 0.05). Also, for similar displacement in T(es), the subjects perceived the immersions at 6 ATA to be less cold than those at 1 ATA (P < 0.05). It is concluded that the development of hypothermia in compressed-air divers may be due, in large part, to the attenuation of heat production and cold perception. Most likely, the observed effects on the autonomic responses and thermal perception are due to an inhibitory action of hyperbaric nitrogen on central neural structures involved in temperature regulation.

  17. Effective parameters in ground roll attenuation using FO CRS stacking

    NASA Astrophysics Data System (ADS)

    Rastegar, Seyyed Ali Fa'al; Javaherian, Abdolrahim; Farajkhah, Naser Keshavarz; Monfared, Mehrdad Soleimani; Zarei, Abbas

    2016-12-01

    Ground roll is a coherent noise in land seismic data that has high energy, high amplitude, low frequency and low velocity. It has to be attenuated in the seismic data processing as it may mask reflections in the zone of ground roll. In this study, we employed common reflection surface for finite offset (FO CRS) to attenuate the ground roll. The FO CRS stacking operator is a hyperbola; therefore, it fits the hyperbolic reflections in the prestack data. Conversely, the ground roll is linear in the common-midpoint (CMP) and common-shot (CS) gathers and can be distinguished and attenuated by the FO CRS operator. Thus, we search for the dip and curvature of the reflections in the CMP section and CS gather prior to the finite-offset section. When the algorithm is specified, the ground roll and reflections have low and high coherency values, respectively. So, any event with non-hyperbolic traveltime, like the linear traveltime ground roll can be removed. We applied the proposed method on a synthetic and an oilfield data from the west of Iran. Results showed that the FO CRS stacking method properly attenuated the ground roll. Further investigations were the effects of spatial aliasing, frequency content, random noise, ground roll dip, the range of dip and curvature scans and reflection amplitudes on ground roll attenuation by the FO CRS stacking. From mentioned parameters, spatial aliasing, frequency content, and random noise had no significant effects. On the contrary, the proposed method turned out to be strongly dependent upon ground roll dip, the range of dip and curvature scans and reflection amplitudes.

  18. Site response and attenuation in the Puget Lowland, Washington State

    USGS Publications Warehouse

    Pratt, T.L.; Brocher, T.M.

    2006-01-01

    Simple spectral ratio (SSR) and horizontal-to-vertical (HN) site-response estimates at 47 sites in the Puget Lowland of Washington State document significant attenuation of 1.5- to 20-Hz shear waves within sedimentary basins there. Amplitudes of the horizontal components of shear-wave arrivals from three local earthquakes were used to compute SSRs with respect to the average of two bedrock sites and H/V spectral ratios with respect to the vertical component of the shear-wave arrivals at each site. SSR site-response curves at thick basin sites show peak amplifications of 2 to 6 at frequencies of 3 to 6 Hz, and decreasing spectra amplification with increasing frequency above 6 Hz. SSRs at nonbasin sites show a variety of shapes and larger resonance peaks. We attribute the spectral decay at frequencies above the amplification peak at basin sites to attenuation within the basin strata. Computing the frequency-independent, depth-dependent attenuation factor (Qs,int) from the SSR spectral decay between 2 and 20 Hz gives values of 5 to 40 for shallow sedimentary deposits and about 250 for the deepest sedimentary strata (7 km depth). H/V site responses show less spectral decay than the SSR responses but contain many of the same resonance peaks. We hypothesize that the H/V method yields a flatter response across the frequency spectrum than SSRs because the H/V reference signal (vertical component of the shear-wave arrivals) has undergone a degree of attenuation similar to the horizontal component recordings. Correcting the SSR site responses for attenuation within the basins by removing the spectral decay improves agreement between SSR and H/V estimates.

  19. Seismic wave attenuation and velocity dispersion in UAE carbonates

    NASA Astrophysics Data System (ADS)

    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

  20. ALDH2 attenuates Dox-induced cardiotoxicity by inhibiting cardiac apoptosis and oxidative stress.

    PubMed

    Gao, Yawen; Xu, Yan; Hua, Songwen; Zhou, Shenghua; Wang, Kangkai

    2015-01-01

    The anthracycline chemotherapy drug doxorubicin (DOX) is cardiotoxic. This study aimed to explore the effect of acetaldehyde dehydrogenase 2 (ALDH2), a detoxifying protein, on DOX-induced cardiotoxicity and unveil the underlying mechanisms. BALB/c mice were randomly divided in four groups: control group (no treatment), DOX group (DOX administration for myocardial damage induction), DOX + Daidzin group (DOX administration + Daidzin, an ALDH2 antagonist) and DOX + Alda-1 group (DOX administration + Alda-1, an ALDH2 agonist). Then, survival, haemodynamic parameters, expression of pro- and anti-apoptosis markers, reactive oxygen species (ROS) and 4-Hydroxynonenal (4-HNE) levels, expression and localization of NADPH oxidase 2 (NOX2) and its cytoplasmic subunit p47(PHOX), and ALDH2 expression and activity were assessed. Mortality rates of 0, 35, 5, and 70% were obtained in the control, DOX, DOX + Alda-1, and DOX + Daidzin groups, respectively, at the ninth weekend. Compared with control animals, DOX treatment resulted in significantly reduced left ventricular systolic pressure (LVSP) and ± dp/dt, and overtly increased left ventricular end-diastolic pressure (LVEDP); increased Bax expression and caspase-3/7 activity, and reduced Bcl-2 expression in the myocardium; increased ROS (about 2 fold) and 4-HNE adduct (3 fold) levels in the myocardium; increased NOX2 protein expression and membrane translocation of P47(PHOX). These effects were aggravated in the DOX + Daidzin group, DOX + Alda-1 treated animals showed partial or complete alleviation. Finally, Daidzin further reduced the DOX-repressed ALDH2 activity, which was partially rescued by Alda-1. These results indicated that ALDH2 attenuates DOX-induced cardiotoxicity by inhibiting oxidative stress, NOX2 expression and activity, and reducing myocardial apoptosis.

  1. Dexmedetomidine ameliorates muscle wasting and attenuates the alteration of hypothalamic neuropeptides and inflammation in endotoxemic rats

    PubMed Central

    Cheng, Minhua; Gao, Tao; Xi, Fengchan; Cao, Chun; Chen, Yan; Zhao, Chenyan; Li, Qiurong

    2017-01-01

    Dexmedetomidine is generally used for sedaton in critically ill, it could shorten duration of mechanical ventilation, ICU stay and lower basic metabolism. However, the exact mechanism of these positive effects remains unkown. Here we investigated the hypothesis that dexmedetomidine could ameliorate muscle wasting in endotoxemic rats and whether it was related to hypothalamic neuropeptides alteration and inflammation. Fourty-eight adult male Sprague–Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) (5 mg/kg) or saline, followed by 50 μg/kg dexmedetomidine or saline administration via the femoral vein catheter (infusion at 5 μg·kg-1·hr-1). Twenty-four hours after injection, hypothalamus tissues and skeletal muscle were obtained. Muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle atrophy F-box (MAFbx) and muscle ring finger 1 (MuRF-1) as well as 3-methylhistidine (3-MH) and tyrosine release. Hypothalamic inflammatory markers and neuropeptides expression were also detected in all four groups. Results showed that LPS administration led to significant increase in hypothalamic inflammation together with muscle wasting. Increased hypothalamic neuropeptides, proopiomelanocortin (POMC), cocaine and amphetamine-related transcript (CART) and neuropeptides Y (NPY) and decreased agouti-related protein (AgRP) were also observed. Meanwhile dexmedetomidine administration ameliorated muscle wasting, hypothalamic inflammation and modulated the alteration of neuropeptides, POMC, CART and AgRP, in endotoxemic rats. In conclusion, dexmedetomidine could alleviate muscle wasting in endotoxemic rats, and it could also attenuate the alteration of hypothalamic neuropeptides and reduce hypothalamic inflammation. PMID:28358856

  2. C-phycocyanin attenuates cisplatin-induced nephrotoxicity in mice.

    PubMed

    Lim, Beom Jin; Jeong, Jin Young; Chang, Yoon-Kyung; Na, Ki-Ryang; Lee, Kang Wook; Shin, Young-Tai; Choi, Dae Eun

    2012-01-01

    Although cisplatin is a highly effective antineoplastic agent, nephrotoxicity is its major clinical problem. Recently, it was reported that Spirulina, a blue-green algae, has potent antioxidant properties. The aim of this study was to establish the possible protective role of C-phycocyanin (PC), one of the active ingredients of Spirulina, against cisplatin-induced nephrotoxicity. This study was carried out using human kidney-2 (HK-2) cells and male C57BL6 mice. Cells and mice were divided into four groups; untreated control group, PC-treated control group, cisplatin-treated group, and PC plus cisplatin-treated group. The molecular, functional, and structural parameters were measured. PC significantly attenuated blood urea nitrogen, serum creatinine, renal histological damages, and apoptotic cell death in cisplatin-treated mice. The cisplatin-induced cell death was significantly attenuated in cells pretreated with PC. PC also significantly attenuated the elevation of p-ERK, p-JNK, and p-p38 induced by cisplatin treatment. The expression of Bax, caspase-9, and caspase-3 in cisplatin-treated cells were also decreased by PC treatment. In conclusion, PC ameliorates cisplatin-induced nephrotoxicity and, at least in part, suppression of p-ERK, p-JNK, p-p38, Bax, caspase-9, and caspase-3 may be involved in this mechanism.

  3. Migrant Education Administrative Guide.

    ERIC Educational Resources Information Center

    North Carolina State Dept. of Public Instruction, Raleigh. Div. of Compensatory Education.

    Relating specifically to the North Carolina migrant education program's administrative responsibilities, this guide is designed to aid administrators in program management, monitoring project activities, project evaluation, self-assessment, determining needs for training and staff development, site-visit preparation, policy development, and…

  4. Champions of Children. Administrators . . .

    ERIC Educational Resources Information Center

    Chaffee, John; Olds, H. Robert

    Today, in an era of taxpayer revolts, lack of clarity in values, and changing family structure, children need advocates in the political arena as well as in the schools. This pamphlet suggests that administrators are in an excellent position to defend the rights of children on all fronts. It focuses on what administrators have done and specific…

  5. The Administrative Power Grab

    ERIC Educational Resources Information Center

    Sorenson, Richard D.

    2007-01-01

    Administrative power for some school teachers can be an aphrodisiac that can be applied negatively, especially when a leader has devastating instinct for the weaknesses of others. A leader's intellect and heart closes shop and ceases to function when drunk on power. In this article, the author describes how the use of administrative power can be…

  6. Traditionalism and Educational Administration.

    ERIC Educational Resources Information Center

    Holmes, Mark

    Administration is defined as the enactment of moral choices influencing subordinates within an organizational setting. It is distinguished from management, which is considered to involve a lower level of discretion. Educational administration is therefore in the moral domain; it involves discretionary, moral choices in a field that is itself moral…

  7. Test Administration Models

    ERIC Educational Resources Information Center

    Becker, Kirk A.; Bergstrom, Betty A.

    2013-01-01

    The need for increased exam security, improved test formats, more flexible scheduling, better measurement, and more efficient administrative processes has caused testing agencies to consider converting the administration of their exams from paper-and-pencil to computer-based testing (CBT). Many decisions must be made in order to provide an optimal…

  8. The Administrative Team.

    ERIC Educational Resources Information Center

    Ohio Association of Elementary School Principals, Westerville.

    Although needs of school districts vary with size, degree of teacher negotiation procedures, and type of community involvement, the administrative team model is presented as an effective, appropriate administrative organization. Based on an assumption that each level of authority in a school district possesses and exercises expertise and unique…

  9. Administrative Theory in Transition.

    ERIC Educational Resources Information Center

    Griffiths, Daniel E.

    This monograph analyzes transition in educational administrative theory. A brief introductory section describes the theoretical movement, the substance and repercussions of Thomas Greenfield's critique of educational administrative theory in 1974, and emerging qualitative approaches. Seven readings, all written by the volume's author, view…

  10. Improving Educational Administrative Decisions.

    ERIC Educational Resources Information Center

    Wolfe, A. E.

    This paper discusses the financial crisis facing public education in the United States today and argues that the most effective response to this crisis is to improve the decision-making skills of educational administrators. Based on a review of the literature on administrative decision-making and organizational change, the author examines several…

  11. Rural Administrative Leadership Handbook.

    ERIC Educational Resources Information Center

    Tift, Carolyn

    This resource book on rural administrative leadership is the result of 1988 interviews with school administrators involved in successful rural educational programs. The material is divided into eight chapters, each self-contained for separate use. Chapter 1, "Getting to Know the Community," addresses qualities of living and working in…

  12. Detailed Study of Seismic Wave Attenuation in Carbonate Rocks: Application on Abu Dhabi Oil Fields

    NASA Astrophysics Data System (ADS)

    Bouchaala, F.; Ali, M. Y.; Matsushima, J.

    2015-12-01

    Seismic wave attenuation is a promising attribute for the petroleum exploration, thanks to its high sensitivity to physical properties of subsurface. It can be used to enhance the seismic imaging and improve the geophysical interpretation which is crucial for reservoir characterization. However getting an accurate attenuation profile is not an easy task, this is due to complex mechanism of this parameter, although that many studies were carried out to understand it. The degree of difficulty increases for the media composed of carbonate rocks, known to be highly heterogeneous and with complex lithology. That is why few attenuation studies were done successfully in carbonate rocks. The main objectives of this study are, Getting an accurate and high resolution attenuation profiles from several oil fields. The resolution is very important target for us, because many reservoirs in Abu Dhabi oil fields are tight.Separation between different modes of wave attenuation (scattering and intrinsic attenuations).Correlation between the attenuation profiles and other logs (Porosity, resistivity, oil saturation…), in order to establish a relationship which can be used to detect the reservoir properties from the attenuation profiles.Comparison of attenuation estimated from VSP and sonic waveforms. Provide spatial distribution of attenuation in Abu Dhabi oil fields.To reach these objectives we implemented a robust processing flow and new methodology to estimate the attenuation from the downgoing waves of the compressional VSP data and waveforms acquired from several wells drilled in Abu Dhabi. The subsurface geology of this area is primarily composed of carbonate rocks and it is known to be highly fractured which complicates more the situation, then we separated successfully the intrinsic attenuation from the scattering. The results show that the scattering is significant and cannot be ignored. We found also a very interesting correlation between the attenuation profiles and the

  13. Soft Tissue Conduction as a Possible Contributor to the Limited Attenuation Provided by Hearing Protection Devices

    PubMed Central

    Chordekar, Shai; Adelman, Cahtia; Sohmer, Haim; Kishon-Rabin, Liat

    2016-01-01

    Context: Damage to the auditory system by loud sounds can be avoided by hearing protection devices (HPDs) such as earmuffs, earplugs, or both for maximum attenuation. However, the attenuation can be limited by air conduction (AC) leakage around the earplugs and earmuffs by the occlusion effect (OE) and by skull vibrations initiating bone conduction (BC). Aims: To assess maximum attenuation by HPDs and possible flanking pathways to the inner ear. Subjects and Methods: AC attenuation and resulting thresholds were assessed using the real ear attenuation at threshold (REAT) procedure on 15 normal-hearing participants in four free-field conditions: (a) unprotected ears, (b) ears covered with earmuffs, (c) ears blocked with deeply inserted customized earplugs, and (d) ears blocked with both earplugs and earmuffs. BC thresholds were assessed with and without earplugs to assess the OE. Results: Addition of earmuffs to earplugs did not cause significantly greater attenuation than earplugs alone, confirming minimal AC leakage through the external meatus and the absence of the OE. Maximum REATs ranged between 40 and 46 dB, leading to thresholds of 46–54 dB HL. Furthermore, calculation of the acoustic impedance mismatch between air and bone predicted at least 60 dB attenuation of BC. Conclusion: Results do not support the notion that skull vibrations (BC) contributed to the limited attenuation provided by traditional HPDs. An alternative explanation, supported by experimental evidence, suggests transmission of sound to inner ear via non-osseous pathways such as skin, soft tissues, and fluid. Because the acoustic impedance mismatch between air and soft tissues is smaller than that between air and bone, air-borne sounds would be transmitted to soft tissues more effectively than to bone, and therefore less attenuation is expected through soft tissue sound conduction. This can contribute to the limited attenuation provided by traditional HPDs. The present study has practical

  14. Immunization with Eimeria ninakohlyakimovae-live attenuated oocysts protect goat kids from clinical coccidiosis.

    PubMed

    Ruiz, Antonio; Muñoz, María Carmen; Molina, José Manuel; Hermosilla, Carlos; Andrada, Marisa; Lara, Pedro; Bordón, Elisa; Pérez, Davinia; López, Adassa María; Matos, Lorena; Guedes, Aránzazu Carmen; Falcón, Soraya; Falcón, Yaiza; Martín, Sergio; Taubert, Anja

    2014-01-17

    Caprine coccidiosis, affecting mainly young goat kids around the weaning period, is worldwide the most important disease in the goat industry. Control of caprine coccidiosis is increasingly hampered by resistances developed against coccidiostatic drugs leading to an enhanced need for anticoccidial vaccines. In the current study we conducted an oral immunization trial with live attenuated sporulated Eimeria ninakohlyakimovae oocysts. Sporulated E. ninakohlyakimovae oocysts were attenuated by X-irradiation technique. The experimental design included a total of 18 goat kids divided into the following groups: (i) animals immunized with attenuated E. ninakohlyakimovae oocysts at 5 weeks of age and challenged 3 weeks later with non-irradiated homologous oocysts (group 1); (ii) animals infected with non-attenuated E. ninakohlyakimovae oocysts at 5 weeks of age and challenged 3 weeks later with non-attenuated homologous oocysts (group 2); (iii) animals primary-infected with untreated E. ninakohlyakimovae oocysts at 8 weeks of age (control of the challenge infection, group 3); (iv) non-infected control animals (group 4). Goat kids immunized with live attenuated E. ninakohlyakimovae oocysts (group 1) excreted significantly less oocysts in the faeces (95.3% reduction) than kids infected with non-attenuated ones (group 2). Furthermore, immunization with live but attenuated oocysts resulted in ameliorated clinical coccidiosis compared to goat kids infected with untreated oocysts (group 2) and resulted in equally reduced signs of coccidiosis after challenge infection compared to acquired immunity driven by non-attenuated oocysts. Overall, the present study demonstrates for the first time that live attenuated E. ninakohlyakimovae oocysts orally administered showed almost no pathogenicity but enough immunogenicity in terms of immunoprotection. Importantly, vaccinated animals still shed low amounts of oocysts, guaranteeing environmental contamination and consecutive booster

  15. Markerless attenuation correction for carotid MRI surface receiver coils in combined PET/MR imaging

    NASA Astrophysics Data System (ADS)

    Eldib, Mootaz; Bini, Jason; Robson, Philip M.; Calcagno, Claudia; Faul, David D.; Tsoumpas, Charalampos; Fayad, Zahi A.

    2015-06-01

    The purpose of the study was to evaluate the effect of attenuation of MR coils on quantitative carotid PET/MR exams. Additionally, an automated attenuation correction method for flexible carotid MR coils was developed and evaluated. The attenuation of the carotid coil was measured by imaging a uniform water phantom injected with 37 MBq of 18F-FDG in a combined PET/MR scanner for 24 min with and without the coil. In the same session, an ultra-short echo time (UTE) image of the coil on top of the phantom was acquired. Using a combination of rigid and non-rigid registration, a CT-based attenuation map was registered to the UTE image of the coil for attenuation and scatter correction. After phantom validation, the effect of the carotid coil attenuation and the attenuation correction method were evaluated in five subjects. Phantom studies indicated that the overall loss of PET counts due to the coil was 6.3% with local region-of-interest (ROI) errors reaching up to 18.8%. Our registration method to correct for attenuation from the coil decreased the global error and local error (ROI) to 0.8% and 3.8%, respectively. The proposed registration method accurately captured the location and shape of the coil with a maximum spatial error of 2.6 mm. Quantitative analysis in human studies correlated with the phantom findings, but was dependent on the size of the ROI used in the analysis. MR coils result in significant error in PET quantification and thus attenuation correction is needed. The proposed strategy provides an operator-free method for attenuation and scatter correction for a flexible MRI carotid surface coil for routine clinical use.

  16. Identification of the attenuation potential of a karst aquifer by an artificial dualtracer experiment with caffeine.

    PubMed

    Hillebrand, Olav; Nödler, Karsten; Licha, Tobias; Sauter, Martin; Geyer, Tobias

    2012-10-15

    Little is known with respect to the attenuation capacity of karst aquifers. Even less is known about the risk posed by emerging micropollutants in these systems. In order to identify the attenuation potential of karst aquifers in-situ and to estimate the risk posed by micropollutants, a dualtracer test was conducted in this study in order to investigate differential transport in the subsurface: The reactive compound caffeine was used as a tracer to indicate the attenuation capacity within the aquifer in-situ. Due to the low limit of quantification, only small amounts of caffeine needed to be injected. To calibrate a model and to visualize the attenuation of caffeine a conservative reference tracer (uranine) is injected simultaneously. The methodology is tested in a well-characterised karst system in southwest Germany. The results indicate a significantly higher attenuation rate than was expected for karst aquifers. The attenuation is decribed as a first-order process. The corresponding half-life is 104 h. This low half-life suggests that a generally assumed low natural attenuation capacity of karst aquifers is unjustified. The observed mass loss of caffeine illustrates the potential of caffeine to be used as reactive tracer for indicating in-situ attenuation capacity within highly hydraulically conductive systems, such as karst aquifers. Due to the high attenuation rate of caffeine it does not pose a threat as a long-time contaminant. In combination with a conservative reference tracer an economical and environmentally benign method is presented in this manuscript for the in-situ determination of the attenuation capacity of highly conductive aquifer systems.

  17. EGFR-TKI, erlotinib, causes hypomagnesemia, oxidative stress, and cardiac dysfunction: attenuation by NK-1 receptor blockade.

    PubMed

    Mak, I Tong; Kramer, Jay H; Chmielinska, Joanna J; Spurney, Christopher F; Weglicki, William B

    2015-01-01

    To determine whether the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib may cause hypomagnesemia, inflammation, and cardiac stress, erlotinib was administered to rats (10 mg · kg(-1)· d(-1)) for 9 weeks. Plasma magnesium decreased progressively between 3 and 9 weeks (-9% to -26%). Modest increases in plasma substance P (SP) occurred at 3 (27%) and 9 (25%) weeks. Neutrophil superoxide-generating activity increased 3-fold, and plasma 8-isoprostane rose 210%, along with noticeable appearance of cardiac perivascular nitrotyrosine. The neurokinin-1 (NK-1) receptor antagonist, aprepitant (2 mg · kg(-1) · d(-1)), attenuated erlotinib-induced hypomagnesemia up to 42%, reduced circulating SP, suppressed neutrophil superoxide activity and 8-isoprostane elevations; cardiac nitrotyrosine was diminished. Echocardiography revealed mild to moderately decreased left ventricular ejection fraction (-11%) and % fractional shortening (-17%) by 7 weeks of erlotinib treatment and significant reduction (-17.5%) in mitral valve E/A ratio at week 9 indicative of systolic and early diastolic dysfunction. Mild thinning of the left ventricular posterior wall suggested early dilated cardiomyopathy. Aprepitant completely prevented the erlotinib-induced systolic and diastolic dysfunction and partially attenuated the anatomical changes. Thus, chronic erlotinib treatment does induce moderate hypomagnesemia, triggering SP-mediated oxidative/inflammation stress and mild-to-moderate cardiac dysfunction, which can largely be corrected by the administration of the SP receptor blocker.

  18. Rhubarb attenuates blood-brain barrier disruption via increased zonula occludens-1 expression in a rat model of intracerebral hemorrhage

    PubMed Central

    WANG, YANG; PENG, FAN; XIE, GUI; CHEN, ZE-QI; LI, HAI-GANG; TANG, TAO; LUO, JIE-KUN

    2016-01-01

    Blood-brain barrier (BBB) disruption is a key pathophysiological factor of intracerebral hemorrhage (ICH). The level of zonula occludens-1 (ZO-1) has been closely associated with the degree of BBB damage, and is an indicator of BBB destruction. The aim of the present study was to evaluate the effects of rhubarb on BBB function in a rat model of ICH. ICH was induced in rats by treatment with type VII collagenase. Sham-operated rats were administered with an equal volume of saline. Following the administration of rhubarb decoction (20 g/kg), neurobehavioral function evaluation and Evans blue extravasation assays were performed at days 1, 3 and 5 after ICH. ZO-1 expression in the brain of ICH-induced rats were analyzed via reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analyses. The results suggested that rhubarb significantly ameliorated neurological symptoms and attenuated BBB permeability. The results of immunohistochemistry and RT-PCR studies indicated that the expression of ZO-1 expression was robust in the sham-operated group and was weak in the vehicle-treated group at day 3. The present data indicated that rhubarb effectively attenuated ICH-induced BBB damage in rats, raising the possibility that rhubarb or its active components may be considered useful as neuroprotective drugs for ICH. The protective mechanisms appeared to involve the preservation of BBB integrity and elevation of ZO-1 protein expression levels. PMID:27347045

  19. Handbook for the ESL/ABE Administrator.

    ERIC Educational Resources Information Center

    Escobar, Joanna Sculley; Daugherty, John

    This 1975 handbook consists of three books to be used, together or independently, by administrators in developing, implementing, and evaluating an adult English-as-a-Second-Language (ESL) program. The first book, an administrator's checklist, is designed as an inventory that specifies succinctly the critical and significant program elements. The…

  20. Preparing College Administrators: Fact and Fancy.

    ERIC Educational Resources Information Center

    Stalcup, Robert J.; Wilson, Jerry L.

    The universality of administrative functions and tasks is sufficiently established to make special preparation programs for any one group of higher education administrators unjustifiable. This thesis is based on research undertaken to determine if significant differences existed in the functions or tasks performed by presidents, vice-presidents of…

  1. Comparison of human adipose stromal vascular fraction and adipose-derived mesenchymal stem cells for the attenuation of acute renal ischemia/reperfusion injury

    PubMed Central

    Zhou, Liuhua; Song, Qun; Shen, Jiangwei; Xu, Luwei; Xu, Zheng; Wu, Ran; Ge, Yuzheng; Zhu, Jiageng; Wu, Jianping; Dou, Quanliang; Jia, Ruipeng

    2017-01-01

    Stem cells therapy has been suggested as a promising option for the treatment of acute kidney injury (AKI). This study was performed to compare the abilities of xenogenic transplantation of human adipose stromal vascular fraction (SVF) and adipose-derived mesenchymal stem cells (AdMSCs) to facilitate the recovery of renal function and structure in a rat model of ischemia/reperfusion (IR) induced AKI. SVF or AdMSCs were transplanted to the injured kidney through intra-parenchymal injection. Significantly improved renal function and reduced tubular injury were observed in SVF and AdMSCs groups. Administration of SVF or AdMSCs contributed to significantly improved cell proliferation and markedly reduced cell apoptosis in parallel with reduced microvascular rarefaction in injured kidney. IR injury resulted in higher levels of inflammatory cytokines, whereas xenogenic transplantation of SVF or AdMSCs reduced but not induced inflammatory cytokines expression. Additionally, in vitro study showed that administration of SVF or AdMSCs could also significantly promote the proliferation and survival of renal tubular epithelial cells underwent hypoxia/reoxygenation injury through secreting various growth factors. However, cell proliferation was significantly promoted in SVF group than in AdMSCs group. In conclusion, our study demonstrated that administration of SVF or AdMSCs was equally effective in attenuating acute renal IR injury. PMID:28276451

  2. Natural attenuation general data guide. Final report

    SciTech Connect

    Kram, M.L.; Goetz, F.

    1999-02-01

    This guide is a decision-making tool to help remedial project managers (RPMs) determine whether natural attenuation can be used as a remedial option at contaminant release sites. Data requirements and methodology to evaluate the potential for using natural attenuation are presented. For sites where the natural attenuation remedial option is implemented, tables of commonly measured parameters, general data collection rationale, and interpretation guidance are included. This format allows the RPM to recognize data gaps, interpret data, construct a conceptual site model, and develop a sampling and analysis plan for evaluation and monitoring purposes.

  3. Quercetin attenuates neuronal death against aluminum-induced neurodegeneration in the rat hippocampus.

    PubMed

    Sharma, D R; Wani, W Y; Sunkaria, A; Kandimalla, R J; Sharma, R K; Verma, D; Bal, A; Gill, K D

    2016-06-02

    Aluminum is a light weight and toxic metal present ubiquitously on earth, which has gained considerable attention due to its neurotoxic effects. It also has been linked ecologically and epidemiologically to several neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Guamanian-Parkinsonian complex and Amyotrophic lateral sclerosis (ALS). The mechanism of aluminum neurotoxicity is poorly understood, but it is well documented that aluminum generates reactive oxygen species (ROS). Enhanced ROS production leads to disruption of cellular antioxidant defense systems and release of cytochrome c (cyt-c) from mitochondria to cytosol resulting in apoptotic cell death. Quercetin (a natural flavonoid) protects it from oxidative damage and has been shown to decrease mitochondrial damage in various animal models of oxidative stress. We hypothesized that if oxidative damage to mitochondria does play a significant role in aluminum-induced neurodegeneration, and then quercetin should ameliorate neuronal apoptosis. Administration of quercetin (10 mg/kg body wt/day) reduced aluminum (10 mg/kg body wt/day)-induced oxidative stress (decreased ROS production, increased mitochondrial superoxide dismutase (MnSOD) activity). In addition, quercetin also prevents aluminum-induced translocation of cyt-c, and up-regulates Bcl-2, down-regulates Bax, p53, caspase-3 activation and reduces DNA fragmentation. Quercetin also obstructs aluminum-induced neurodegenerative changes in aluminum-treated rats as seen by Hematoxylin and Eosin (H&E) staining. Further electron microscopic studies revealed that quercetin attenuates aluminum-induced mitochondrial swelling, loss of cristae and chromatin condensation. These results indicate that treatment with quercetin may represent a therapeutic strategy to attenuate the neuronal death against aluminum-induced neurodegeneration.

  4. Single exposure of dopamine D1 antagonist prevents and D2 antagonist attenuates methylphenidate effect

    PubMed Central

    Claussen, Catherine M; Witte, Lindsey J; Dafny, Nachum

    2015-01-01

    Methylphenidate (MPD) is a readily prescribed drug for the treatment of attention deficit hyperactivity disorder (ADHD) and moreover is used illicitly by youths for its cognitive-enhancing effects and recreation. MPD exposure in rodents elicits increased locomotor activity. Repetitive MPD exposure leads to further augmentation of their locomotor activity. This behavioral response is referred to as behavioral sensitization. Behavioral sensitization is used as an experimental marker for a drug’s ability to elicit dependence. There is evidence that dopamine (DA) is a key player in the acute and chronic MPD effect; however, the role of DA in the effects elicited by MPD is still debated. The objective of this study was to investigate the role of D1 and/or D2 DA receptors in the acute and chronic effect of MPD on locomotor activity. The study lasted for 12 consecutive days. Seven groups of male Sprague Dawley® rats were used. A single D1 or D2 antagonist was given before and after acute and chronic MPD administration. Single injection of D1 DA antagonist was able to significantly attenuate the locomotor activity when given prior to the initial MPD exposure and after repetitive MPD exposure, while the D2 DA antagonist partially attenuated the locomotor activity only when given before the second MPD exposure. The results show the role, at least in part, of the D1 DA receptor in the mechanism of behavioral sensitization, whereas the D2 DA receptor only partially modulates the response to acute and chronic MPD. PMID:27186140

  5. Clopidogrel attenuates lithium-induced alterations in renal water and sodium channels/transporters in mice.

    PubMed

    Zhang, Yue; Peti-Peterdi, János; Heiney, Kristina M; Riquier-Brison, Anne; Carlson, Noel G; Müller, Christa E; Ecelbarger, Carolyn M; Kishore, Bellamkonda K

    2015-12-01

    Lithium (Li) administration causes deranged expression and function of renal aquaporins and sodium channels/transporters resulting in nephrogenic diabetes insipidus (NDI). Extracellular nucleotides (ATP/ADP/UTP), via P2 receptors, regulate these transport functions. We tested whether clopidogrel bisulfate (CLPD), an antagonist of ADP-activated P2Y(12) receptor, would affect Li-induced alterations in renal aquaporins and sodium channels/transporters. Adult mice were treated for 14 days with CLPD and/or Li and euthanized. Urine and kidneys were collected for analysis. When administered with Li, CLPD ameliorated polyuria, attenuated the rise in urine prostaglandin E2 (PGE2), and resulted in significantly higher urinary arginine vasopressin (AVP) and aldosterone levels as compared to Li treatment alone. However, urine sodium excretion remained elevated. Semi-quantitative immunoblotting revealed that CLPD alone increased renal aquaporin 2 (AQP2), Na-K-2Cl cotransporter (NKCC2), Na-Cl cotransporter (NCC), and the subunits of the epithelial Na channel (ENaC) in medulla by 25-130 %. When combined with Li, CLPD prevented downregulation of AQP2, Na-K-ATPase, and NKCC2 but was less effective against downregulation of cortical α- or γ-ENaC (70 kDa band). Thus, CLPD primarily attenuated Li-induced downregulation of proteins involved in water conservation (AVP-sensitive), with modest effects on aldosterone-sensitive proteins potentially explaining sustained natriuresis. Confocal immunofluorescence microscopy revealed strong labeling for P2Y(12)-R in proximal tubule brush border and blood vessels in the cortex and less intense labeling in medullary thick ascending limb and the collecting ducts. Therefore, there is the potential for CLPD to be directly acting at the tubule sites to mediate these effects. In conclusion, P2Y(12)-R may represent a novel therapeutic target for Li-induced NDI.

  6. Active vaccination attenuates the psychostimulant effects of α-PVP and MDPV in rats.

    PubMed

    Nguyen, Jacques D; Bremer, Paul T; Ducime, Alex; Creehan, Kevin M; Kisby, Brent R; Taffe, Michael A; Janda, Kim D

    2016-12-09

    Recreational use of substituted cathinones continues to be an emerging public health problem in the United States; cathinone derivatives α-pyrrolidinopentiophenone (α-PVP) and 3,4-methylenedioxypyrovalerone (MDPV), which have been linked to human fatalities and show high potential for abuse liability in animal models, are of particular concern. The objective of this study was to develop an immunotherapeutic strategy for attenuating the effects of α-PVP and MDPV in rats, using drug-conjugate vaccines created to generate antibodies with neutralizing capacity. Immunoconjugates (α-PVP-KLH and MDPV-KLH) or the control carrier protein, keyhole limpet hemocyanin (KLH), were administered to groups (N = 12) of male Sprague-Dawley rats on Weeks 0, 2 and 4. Groups were administered α-PVP or MDPV (0.0, 0.25, 0.5, 1.0, 5.0 mg/kg, i.p.) in acute drug challenges and tested for changes in wheel activity. Increased wheel activity produced by α-PVP or MDPV in the controls was attenuated in the α-PVP-KLH and MDPV-KLH vaccinated groups, respectively. Rectal temperature decreases produced by MDPV in the controls were reduced in duration in the MDPV-KLH vaccine group. A separate group (N = 19) was trained to intravenously self-administer α-PVP (0.05, 0.1 mg/kg/inf) and vaccinated with KLH or α-PVP-KLH, post-acquisition. Self-administration in α-PVP-KLH rats was initially higher than in the KLH rats but then significantly decreased following a final vaccine booster, unlike the stable intake of KLH rats. The data demonstrate that active vaccination provides functional protection against the effects of α-PVP and MDPV, in vivo, and recommend additional development of vaccines as potential therapeutics for mitigating the effects of designer cathinone derivatives.

  7. Intranasal delivery of nerve growth factor attenuates aquaporins-4-induced edema following traumatic brain injury in rats.

    PubMed

    Lv, Qiushi; Fan, Xinying; Xu, Gelin; Liu, Qian; Tian, Lili; Cai, Xiaoyi; Sun, Wenshan; Wang, Xiaomeng; Cai, Qiankun; Bao, Yuanfei; Zhou, Lulu; Zhang, Yao; Ge, Liang; Guo, Ruibing; Liu, Xinfeng

    2013-02-01

    Traumatic brain injury (TBI) remains the leading cause of injury-related death and disability. Brain edema, one of the most major complications of TBI, contributes to elevated intracranial pressure, and poor prognosis following TBI. Nerve growth factor (NGF) appears to be a viable strategy to treat brain edema and TBI. Unfortunately, due to its poor blood-brain barrier (BBB) permeability, the clinical application of NGF has been greatly limited. We previously demonstrated that intranasal NGF could bypass the BBB and distribute throughout the brain. Here we further studied whether intranasal NGF could attenuate TBI-induced brain edema and its putative mechanisms. TBI was produced by a modified weight-drop model. We found that intranasal administration of NGF (5μg/d) attenuated the brain edema, as assayed by hemisphere water content, at 12h, 24h and 72h after TBI induction. This attenuation was associated with a prominent decrease of the content of aquaporin-4, which plays a pivotal role in the formation of brain edema. By the use of RT-PCR and ELISA, we showed that intranasal NGF markedly inhibited the transcription and expression of pro-inflammatory cytokines including IL-1β and TNF-α. An electrophoretic mobility shift assay (EMSA) displayed a significant activation of nuclear factor-κB following TBI, which was, however, much lowered in the NGF-treated rats. Furthermore, upon intranasal NGF supplementation, mitochondria-mediated apoptosis following TBI was minimized, as indicated by upregulation of Bcl-2 and downregulation of caspase-3. Collectively, our findings suggested that intranasal NGF may be a promising strategy to treat brain edema and TBI.

  8. Peripheral δ-opioid receptors attenuate the exercise pressor reflex.

    PubMed

    Leal, Anna K; Yamauchi, Katsuya; Kim, Joyce; Ruiz-Velasco, Victor; Kaufman, Marc P

    2013-10-15

    In rats with ligated femoral arteries, the exercise pressor reflex is exaggerated, an effect that is attenuated by stimulation of peripheral μ-opioid receptors on group IV metabosensitive afferents. In contrast, δ-opioid receptors are expressed mostly on group III mechanosensitive afferents, a finding that prompted us to determine whether stimulation of these opioid receptors could also attenuate the exaggerated exercise pressor reflex in "ligated" rats. We found femoral arterial injection of [D-Pen2,D-Pen5]enkephalin (DPDPE; 1.0 μg), a δ-opioid agonist, significantly attenuated the pressor and cardioaccelerator components of the exercise pressor reflex evoked by hindlimb muscle contraction in both rats with ligated and patent femoral arteries. DPDPE significantly decreased the pressor responses to muscle mechanoreflex activation, evoked by tendon stretch, in ligated rats only. DPDPE (1.0 μg) had no effect in either group on the pressor and cardioaccelerator responses to capsaicin (0.2 μg), which primarily stimulates group IV afferents. DPDPE (1.0 μg) had no effect on the pressor and cardioaccelerator responses to lactic acid (24 mM), which stimulates group III and IV afferents, in rats with patent femoral arteries but significantly decreased the pressor response in ligated rats. Western blots revealed the amount of protein comprising the δ-opioid receptor was greater in dorsal root ganglia innervating hindlimbs with ligated femoral arteries than in dorsal root ganglia innervating hindlimbs with patent femoral arteries. Our findings support the hypothesis that stimulation of δ-opioid receptors on group III afferents attenuated the exercise pressor reflex.

  9. Peripheral δ-opioid receptors attenuate the exercise pressor reflex

    PubMed Central

    Yamauchi, Katsuya; Kim, Joyce; Ruiz-Velasco, Victor; Kaufman, Marc P.

    2013-01-01

    In rats with ligated femoral arteries, the exercise pressor reflex is exaggerated, an effect that is attenuated by stimulation of peripheral μ-opioid receptors on group IV metabosensitive afferents. In contrast, δ-opioid receptors are expressed mostly on group III mechanosensitive afferents, a finding that prompted us to determine whether stimulation of these opioid receptors could also attenuate the exaggerated exercise pressor reflex in “ligated” rats. We found femoral arterial injection of [D-Pen2,D-Pen5]enkephalin (DPDPE; 1.0 μg), a δ-opioid agonist, significantly attenuated the pressor and cardioaccelerator components of the exercise pressor reflex evoked by hindlimb muscle contraction in both rats with ligated and patent femoral arteries. DPDPE significantly decreased the pressor responses to muscle mechanoreflex activation, evoked by tendon stretch, in ligated rats only. DPDPE (1.0 μg) had no effect in either group on the pressor and cardioaccelerator responses to capsaicin (0.2 μg), which primarily stimulates group IV afferents. DPDPE (1.0 μg) had no effect on the pressor and cardioaccelerator responses to lactic acid (24 mM), which stimulates group III and IV afferents, in rats with patent femoral arteries but significantly decreased the pressor response in ligated rats. Western blots revealed the amount of protein comprising the δ-opioid receptor was greater in dorsal root ganglia innervating hindlimbs with ligated femoral arteries than in dorsal root ganglia innervating hindlimbs with patent femoral arteries. Our findings support the hypothesis that stimulation of δ-opioid receptors on group III afferents attenuated the exercise pressor reflex. PMID:23934854

  10. Green tea polyphenols and 1-α-OH-vitamin D₃ attenuate chronic inflammation-induced myocardial fibrosis in female rats.

    PubMed

    Shen, Chwan-Li; Samathanam, Christina; Graham, Suzanne; Dagda, Raul Y; Chyu, Ming-Chien; Dunn, Dale M

    2012-03-01

    Studies have suggested that 1-α-OH-vitamin D₃ and green tea polyphenols (GTPs) are promising dietary supplements for mitigating chronic inflammation-induced fibrosis of vessels because of their anti-inflammatory properties. This study evaluated (1) the impact of 1-α-OH-vitamin D₃ on myocardial fibrosis in female rats with chronic inflammation and (2) if 1-α-OH-vitamin D₃ and GTPs have an additive or synergistic effect to attenuate myocardial fibrosis in these female rats. A 3-month study of a 2 (no 1-α-OH-vitamin D₃ vs. 0.05 μg/kg 1-α-OH-vitamin D₃, five times per week) ×2 (no GTPs vs. 0.5% GTPs in drinking water) factorial design in lipopolysaccharide (LPS)-administered female rats was performed. Additionally, a group receiving placebo administration was used to compare with a group receiving LPS administration only to evaluate the effect of LPS. Masson's Trichrome staining evaluated myocardial fibrosis in coronary vessels and surrounding myocardium. Spleen cyclooxygenase-2 mRNA expression was determined by real-time polymerase chain reaction. Total lipid profiles were also determined. Whole blood was used for differential cell counts. Data were analyzed by two-way analysis of variance followed by mean separation procedures. At 3 months LPS administration induced myocardial fibrosis in vessels and surrounding myocardium, spleen cyclooxygenase-2 mRNA expression, and elevated leukocyte counts, whereas both 1-α-OH-vitamin D₃ administration and GTPs supplementation significantly attenuated these pro-inflammatory events. The inhibitory effects of 1-α-OH-vitamin D₃ and GTPs seem to be an individual effect, instead of an additive or synergistic effect. 1-α-OH-vitamin D₃ and GTPs lowered red blood cell counts, hematocrit, and hemoglobin. Neither 1-α-OH-vitamin D₃ nor GTPs affected lipid profiles. In summary, both 1-α-OH-vitamin D₃ administration and GTPs supplementation mitigate myocardial fibrosis through suppression of a chronic

  11. The non-steroidal anti-inflammatory drug diclofenac sodium attenuates lipopolysaccharide-induced alterations to reward behavior and corticosterone release.

    PubMed

    De La Garza, Richard; Fabrizio, Kevin R; Radoi, Gina Elena; Vlad, Tudor; Asnis, Gregory M

    2004-02-04

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to counteract stress hormone and pro-inflammatory cytokine activation. To extend these findings, we tested whether the NSAID diclofenac sodium would attenuate lipopolysaccharide (LPS)-induced reductions in reward behavior. In the first experiment, male, Wistar rats pressed a lever for food reward and subsequently received 10 days treatment of saline (1 ml/kg, s.c.) or diclofenac (2.5mg/kg, s.c.). On the subsequent test day, rats were given a final injection of saline or diclofenac 30 min prior to LPS (20 micrograms/kg, i.p.). LPS significantly reduced rate of food self-administration and total reinforcers obtained and increased corticosterone levels in saline-treated rats, while these effects were significantly attenuated in diclofenac-treated rats. In the second experiment, rats pressed a lever for sweetened milk. In contrast to food self-administration, acute LPS exposure did not reduce rate of responding or total reinforcers obtained in either saline- or diclofenac-treated rats. In the third experiment, rats trained to press a lever for sweetened milk were pre-exposed to a high dose of LPS (250 micrograms/kg, i.p.) 2 weeks prior to a challenge injection of LPS. In this case, LPS challenge significantly reduced rate of sweetened milk self-administration, but not total reinforcers obtained, in saline-treated rats. Rats treated with diclofenac did not exhibit reductions in rate of responding or total reinforcers obtained. Overall, the data indicate that the NSAID diclofenac sodium counteracts LPS-induced reductions in reward behavior and corticosterone release, and may therefore have therapeutic potential for specific components of endotoxin-induced sickness behavior, including anhedonia.

  12. Safe administration of blood components.

    PubMed

    Hurrell, Katy

    The transfusion process has many stages, each involving different members of staff in different locations. This gives rise to a significant potential for errors. Nurses are involved in many of these stages and therefore require knowledge, skills and competence in the process to ensure the safety of patients. This third article in our five-part series on blood transfusion discusses the safe administration of blood components and the key principles to which nurses must adhere.

  13. Protective effect of co-administration of curcumin and sildenafil in alcohol induced neuropathy in rats.

    PubMed

    Kaur, Maninder; Singh, Amarjeet; Kumar, Bimlesh; Singh, Sachin Kumar; Bhatia, Amit; Gulati, Monica; Prakash, T; Bawa, Palak; Malik, Adil Hussain

    2017-03-16

    Neuropathic pain associated with chronic alcohol consumption is a medico-socioeconomical problem that affects both central and peripheral nervous system and has no satisfactory treatment till date. The present study was designed to investigate the protective effect of co-administration of curcumin and sildenafil on alcohol induced neuropathic pain in rats. In order to carry out this, ethanol (35% v/v, 10g/kg, p.o.) was administered for 10 weeks to induce neuropathic pain. Curcumin (30 and 60mg/kg, i.p.) and sildenafil (5 and 10mg/kg, i.p.) were given alone and in combination at their lower doses (30mg/kg curcumin and 5mg/kg, sildenafil, i.p.) to investigate the changes in thermal and mechanical hyperalgesia, allodynia and histopathological parameters. Biochemical estimations of thiobarbituric acid reactive species, glutathione and protein was also carried out to evaluate oxidative stress. The results revealed that chronic alcohol consumption for 10 weeks caused significant thermal and mechanical hyperalgesia, allodynia and increased oxidative stress. Individual administration of both the drugs at their low as well as high doses were able to improve the symptoms of alcohol induced neuropathic pain. Whereas co-administration of curcumin and sildenafil at their lower doses itself were found to significantly improve nerve functions, biochemical and histopathological parameters as compared to their individual administration. It is therefore proposed that co-administration of curcumin and sildenafil may bring new dimension towards attenuation of alcohol induced neuropathic pain affecting central as well as peripheral nervous system.

  14. A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha.

    PubMed

    Lee, Kyung Sun; Kim, So Ri; Park, Hee Sun; Park, Seoung Ju; Min, Kyung Hoon; Lee, Ka Young; Choe, Yeong Hun; Hong, Sang Hyun; Han, Hyo Jin; Lee, Young Rae; Kim, Jong Suk; Atlas, Daphne; Lee, Yong Chul

    2007-12-31

    Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.

  15. NEMO-Binding Domain Peptide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting the NF-κB Signaling Pathway

    PubMed Central

    Huang, Jianhua; Li, Li; Yuan, Weifeng; Zheng, Linxin

    2016-01-01

    The aim of the present study is to investigate the protective effects and relevant mechanisms exerted by NEMO-binding domain peptide (NBD) against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. The ALI model was induced by intratracheally administered atomized LPS (5 mg/kg) to BABL/c mice. Half an hour before LPS administration, we treated the mice with increasing concentrations of intratracheally administered NBD or saline aerosol. Two hours after LPS administration, each group of mice was sacrificed. We observed that NBD pretreatment significantly attenuated LPS-induced lung histopathological injury in a dose-dependent manner. Western blotting established that NBD pretreatment obviously attenuated LPS-induced IκB-α and NF-κBp65 activation and NOX1, NOX2, and NOX4 overexpression. Furthermore, NBD pretreatment increased SOD and T-AOC activity and decreased MDA levels in lung tissue. In addition, NBD also inhibited TNF-α and IL-1β secretion in BALF after LPS challenge. In conclusion, NBD protects against LPS-induced ALI in mice. PMID:27956761

  16. Supplementation of parenteral nutrition with fish oil attenuates acute lung injury in a rat model

    PubMed Central

    Kohama, Keisuke; Nakao, Atsunori; Terashima, Mariko; Aoyama-Ishikawa, Michiko; Shimizu, Takayuki; Harada, Daisuke; Nakayama, Mitsuo; Yamashita, Hayato; Fujiwara, Mayu; Kotani, Joji

    2014-01-01

    Fish oil rich in n-3 polyunsaturated fatty acids has diverse immunomodulatory properties and attenuates acute lung injury when administered in enternal nutrition. However, enteral nutrition is not always feasible. Therefore, we investigated the ability of parenteral nutrition supplemented with fish oil to ameliorate acute lung injury. Rats were infused with parenteral nutrition solutions (without lipids, with soybean oil, or with soybean oil and fish oil) for three days. Lipopolysaccharide (15 mg/kg) was then administered intratracheally to induce acute lung injury, characterized by impaired lung function, polymorphonuclear leukocyte recruitment, parenchymal tissue damage, and upregulation of mRNAs for inflammatory mediators. Administration of parenteral nutrition supplemented with fish oil prior to lung insult improved gas exchange and inhibited neutrophil recruitment and upregulation of mRNAs for inflammatory mediators. Parenteral nutrition supplemented with fish oil also prolonged survival. To investigate the underlying mechanisms, leukotriene B4 and leukotriene B5 secretion was measured in neutrophils from the peritoneal cavity. The neutrophils from rats treated with fish oil-rich parenteral nutrition released significantly more leukotriene B5, an anti-inflammatory eicosanoid, than neutrophils isolated from rats given standard parenteral nutrition. Parenteral nutrition with fish oil significantly reduced lipopolysaccharide-induced lung injury in rats in part by promoting the synthesis of anti-inflammatory eicosanoids. PMID:24688221

  17. Hydrogen sulfide attenuates lipopolysaccharide-induced cognitive impairment: a pro-inflammatory pathway in rats.

    PubMed

    Gong, Qi-Hai; Wang, Qian; Pan, Li-Long; Liu, Xin-Hua; Huang, Hui; Zhu, Yi-Zhun

    2010-07-01

    The present study investigated the effect of sodium hydrosulfide (NaHS), a H(2)S donor, on cognitive impairment and neuroinflammatory changes induced by bilateral intracerebroventricular injections of LPS at a dose of 10mug/rat. Rats received 5mg/kg NaHS or volume-matched vehicle administration by intraperitoneal injection 3days before LPS injection then for 9days once daily. Morris water maze was used to detect the cognitive function. Compared to the sham-treated rats, LPS injection significantly prolonged the mean escape latency in the navigation test (P<0.05) and shortened the adjusted escape latency by approximately 30% (P<0.05). Meanwhile, LPS injection decreased H(2)S level but increased pro-inflammatory mediators (i.e., TNF-alpha, TNFR1, degradation of IkappaB-alpha and thereafter activation of NF-kappaB) in hippocampus. However, these effects of LPS were significantly ameliorated with NaHS treatment (P<0.05 vs vehicle-treated group). The present data suggest that H(2)S attenuates LPS-induced cognitive impairment through reducing the overproduction of pro-inflammatory mediators via inhibition of NF-kappaB pathways in rats. This study sets the stage for exploring a novel H(2)S releasing agent for preventing or retarding the development or progression of neurological disorders such as Alzheimer's disease.

  18. Silibinin attenuates allergic airway inflammation in mice

    SciTech Connect

    Choi, Yun Ho; Jin, Guang Yu; Guo, Hui Shu; Piao, Hong Mei; Li, Liang chang; Li, Guang Zhao; Lin, Zhen Hua; Yan, Guang Hai

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  19. Attenuation of external Bremsstrahlung in metallic absorbers

    SciTech Connect

    Dhaliwal, A.S.; Powar, M.S.; Singh, M. )

    1990-12-01

    In this paper attenuation of bremsstrahlung from {sup 147}Pm and {sup 170}Tm beta emitters has been studied in aluminum, copper, tin, and lead metallic absorbers. Bremsstrahlung spectra and mass attenuation coefficients for monoenergetic gamma rays are used to calculate theoretical attenuation curves. Magnetic deflection and beta stopping techniques are used to measure the integral bremsstrahlung intensities above 30 keV in different target thicknesses. Comparison of measured and calculated attenuation curves shows a good agreement for various absorbers, thus providing a test of this technique, which may be useful in understanding bremsstrahlung intensity buildup and in the design of optimum shielding for bremsstrahlung sources. It is found that the absorption of bremsstrahlung in metallic absorbers does not obey an exponential law and that absorbers act as energy filters.

  20. Evolution of Natural Attenuation Evaluation Protocols

    EPA Science Inventory

    Traditionally the evaluation of the efficacy of natural attenuation was based on changes in contaminant concentrations and mass reduction. Statistical tools and models such as Bioscreen provided evaluation protocols which now are being approached via other vehicles including m...

  1. Attenuated retroreflectors for electronic distance measurement

    NASA Astrophysics Data System (ADS)

    Parker, David H.; Goldman, Michael A.; Radcliff, Bill; Shelton, John W.

    Methods are described for attenuating solid glass and hollow retroreflectors, without introducing optical path length modifications, for electronic distance measurement. Construction of a prototype novel-design hollow retroreflector is described.

  2. Scattering error corrections for in situ absorption and attenuation measurements.

    PubMed

    McKee, David; Piskozub, Jacek; Brown, Ian

    2008-11-24

    Monte Carlo simulations are used to establish a weighting function that describes the collection of angular scattering for the WETLabs AC-9 reflecting tube absorption meter. The equivalent weighting function for the AC-9 attenuation sensor is found to be well approximated by a binary step function with photons scattered between zero and the collection half-width angle contributing to the scattering error and photons scattered at larger angles making zero contribution. A new scattering error correction procedure is developed that accounts for scattering collection artifacts in both absorption and attenuation measurements. The new correction method does not assume zero absorption in the near infrared (NIR), does not assume a wavelength independent scattering phase function, but does require simultaneous measurements of spectrally matched particulate backscattering. The new method is based on an iterative approach that assumes that the scattering phase function can be adequately modeled from estimates of particulate backscattering ratio and Fournier-Forand phase functions. It is applied to sets of in situ data representative of clear ocean water, moderately turbid coastal water and highly turbid coastal water. Initial results suggest significantly higher levels of attenuation and absorption than those obtained using previously published scattering error correction procedures. Scattering signals from each correction procedure have similar magnitudes but significant differences in spectral distribution are observed.

  3. Attenuated oncolytic Measles Virus strains as cancer therapeutics

    PubMed Central

    Msaouel, P.; Iankov, I.D.; Dispenzieri, A.; Galanis, E.

    2011-01-01

    Attenuated measles virus vaccine strains have emerged as a promising oncolytic vector platform, having shown significant anti-tumor activity against a broad range of malignant neoplasms. Measles virus strains derived from the attenuated Edmonston-B (MV-Edm) vaccine lineage have been shown to selectively infect, replicate in and lyse cancer cells while causing minimal cytopathic effect on normal tissues. This review summarizes the preclinical data that led to the rapid clinical translation of oncolytic measles vaccine strains and provides an overview of early clinical data using this oncolytic platform. Furthermore, novel approaches currently under development to further enhance the oncolytic efficacy of MV-Edm strains, including strategies to circumvent immunity or modulate immune system responses, combinatorial approaches with standard treatment modalities, virus retargeting as well as strategies for in vivo monitoring of viral replication are discussed. PMID:21740361

  4. Wave speed propagation measurements on highly attenuative heated materials

    SciTech Connect

    Moore, David G.; Ober, Curtis C.; Rodacy, Phil J.; Nelson, Ciji L.

    2015-09-19

    Ultrasonic wave propagation decreases as a material is heated. Two factors that can characterize material properties are changes in wave speed and energy loss from interactions within the media. Relatively small variations in velocity and attenuation can detect significant differences in microstructures. This paper discusses an overview of experimental techniques that document the changes within a highly attenuative material as it is either being heated or cooled from 25°C to 90°C. The experimental set-up utilizes ultrasonic probes in a through-transmission configuration. The waveforms are recorded and analyzed during thermal experiments. To complement the ultrasonic data, a Discontinuous-Galerkin Model (DGM) was also created which uses unstructured meshes and documents how waves travel in these anisotropic media. This numerical method solves particle motion travel using partial differential equations and outputs a wave trace per unit time. As a result, both experimental and analytical data are compared and presented.

  5. Numerical support of laboratory experiments: Attenuation and velocity estimations

    NASA Astrophysics Data System (ADS)

    Saenger, Erik; Madonna, Claudio; Frehner, Marcel; Almqvist, Bjarne

    2014-02-01

    We show that numerical support of laboratory experiments can significantly increase the understanding and simplify the interpretation of the obtained laboratory results. First we perform simulations of the Seismic Wave Attenuation Module to measure seismic attenuation of reservoir rocks. Our findings confirm the accuracy of this system. However, precision can be further improved by optimizing the sensor positions. Second, we model wave propagation for an ultrasonic pulse transmission experiment used to determine pressure- and temperature-dependent seismic velocities in the rock. Multiple waves are identified in our computer experiment, including bar waves. The metal jacket that houses the sample assembly needs to be taken into account for a proper estimation of the ultrasonic velocities. This influence is frequency-dependent.

  6. Electron Effective-Attenuation-Length Database

    National Institute of Standards and Technology Data Gateway

    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).

  7. Ultrasonic Attenuation in Normal and Superconducting Indium.

    DTIC Science & Technology

    1980-05-22

    Bardeen et al, Phys. Rev. 108, 1175), there is an additional source of attenuation. This DD I° 7 1473 EDITION OF NOV S E UNCLASSIFIED SECURITY...electronic attenuation described quantitatively by the BCS theory of super- conductivity ( Bardeen et al., Phys. Rev. 108, 1175), there is an additional source...single crystal of C lead at 26.5 MHz is shown in Figure 1. This phenomenon was first explained quantitatively by Bardeen ,Cooper, and Schrieffer (1957

  8. Drug Education for Administrators

    ERIC Educational Resources Information Center

    Hackett, Peter; McKeon, Thomas L.

    1976-01-01

    The formulation of a drug policy and the implementation of that policy in a firm but fair manner are the responsibility of the school administrator. Authors give serious consideration to this responsibility. (Editor/RK)

  9. Food and Drug Administration

    MedlinePlus

    ... blog post. April 11, 2017 ‘Organs-on-Chips’ Technology: FDA Testing Groundbreaking Science More FDA Voice Blog ... FEAR Act Site Map Nondiscrimination Website Policies U.S. Food and Drug Administration 10903 New Hampshire Avenue Silver ...

  10. Administrative Law Judges

    EPA Pesticide Factsheets

    The Administrative Law Judges conduct hearings and render decisions in proceedings between the EPA and persons, businesses, government entities, and other organizations which are or are alleged to be regulated under environmental laws.

  11. Needed: Nursing Administration Leaders

    ERIC Educational Resources Information Center

    Blair, Eunice M.

    1976-01-01

    A master's program that synthesizes clinical nursing knowledge with management theory and skills is one way to prepare nursing service administrat